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1.  Analysis of Clinical Features and Outcome of 356 Triple-Negative Breast Cancer Patients in China 
Breast Care  2012;7(1):13-17.
The purpose of this study was to investigate the clinicopathological features and analyze the prognostic factors of triple-negative breast cancer (TNBC).
Patients and Methods
The clinical data of 1,788 breast cancer patients was collected and analyzed. The Kaplan-Meier method was used to estimate survival. Multivariate analysis of the prognostic factors for survival was performed using the Cox regression model.
Patients with TNBC exhibited characteristics significantly differing from those with non-TNBC. There was a higher proportion of patients with age < 35 years, stage III disease, tumor size > 5 cm, lymph node positivity, and histological grade 3. The 5-year disease-free survival (DFS) rates of TNBC and non-TNBC patients were 75.7 and 79.6%, respectively (p < 0.05). 5-year overall survival (OS) was 86.6 and 93.5%, respectively (p < 0.05). In multivariate Cox regression analysis, the independent prognostic factors for shorter DFS were age < 35 years (hazard ratio (HR) 2.105), positive lymph nodes (HR 7.039), histological grade 3 (HR 1.841), and for shorter OS positive lymph nodes (HR 4.626).
The proportion of TNBC in breast cancer in China is higher than in other areas. TNBC is correlated with younger age, larger tumor size, positive lymph nodes, higher clinical stage and histological grade, and lower DFS and OS, which is consistent with previous reports.
PMCID: PMC3335351  PMID: 22553467
Triple-negative breast cancer: clinical features, prognosis; Multivariate analysis
2.  Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series 
BMC Cancer  2013;13:15.
Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit.
In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes.
Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05).
Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially.
Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology.
PMCID: PMC3598199  PMID: 23305429
Breast cancer; Mode of detection; Screening; Molecular categories; Survival outcomes
3.  Multivariate survival analysis of the patients with recurrent endometrial cancer 
Few studies on the prognosticators of the patients with recurrent endometrial cancer after relapse have been reported in the literature. The aim of this study was to determine the prognosticators after relapse in patients with recurrent endometrial cancer who underwent primary complete cytoreductive surgery and adjuvant chemotherapy.
Thirty-five patients with recurrent endometrial cancer were included in this retrospective analysis. The prognostic significance of several clinicopathological factors including histologic type, risk for recurrence, time to relapse after primary surgery, number of relapse sites, site of relapse, treatment modality, and complete resection of recurrent tumors were evaluated. Survival analyses were performed by Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis.
Among the clinicopathological factors analyzed, histologic type (p=0.04), time to relapse after primary surgery (p=0.03), and the number of relapse sites (p=0.03) were significantly related to survival after relapse. Multivariate analysis revealed that time to relapse after primary surgery (hazard ratio, 6.8; p=0.004) and the number of relapse sites (hazard ratio, 11.1; p=0.002) were independent prognostic factors for survival after relapse. Survival after relapse could be stratified into three groups by the combination of two independent prognostic factors.
We conclude that time to relapse after primary surgery, and the number of relapse sites were independent prognostic factors for survival after relapse in patients with recurrent endometrial cancer.
PMCID: PMC3097331  PMID: 21607089
Endometrial cancer; Recurrence; Prognostic factor; Multivariate analysis
4.  Treatment Failure after Extrapleural Pneumonectomy for Malignant Pleural Mesothelioma 
Journal of Thoracic Disease  2009;1(1):23-28.
Extrapleural pneumonectomy (EPP) has been used as a treatment option for selected patients with malignant pleural mesothelioma (MPM). The primary end-point of this study was disease-free survival (DFS). Prognostic indicators for local and overall DFS were statistically analyzed.
Between October 1994 to April 2008, 59 patients who had complete macroscopic cytoreduction after EPP formed the basis of this report. In recent years, selected patients received adjuvant radiotherapy and pemetrexed combined with cisplatin or carboplatin. The clinicopathologic data of all patients were prospectively collected in a computerized database. Statistical analysis was performed by using Kaplan-Meier method and compared using the log-rank test. Cox-regression model was used for multivariate analysis.
The mean age at the time of EPP was 59 (S.D. = 8) years. Nineteen patients (32%) experienced perioperative complications. The median survival was 21 months (range 2 to 104). The local disease recurrence rate was 51%. The median local DFS was 22 months (0 to 73). The overall disease recurrence rate was 64%. The median overall DFS was 18 months (range 0 to 73). In multivariate analysis, epithelial subtype (p = 0.026) and adjuvant radiotherapy (p = 0.023) were independently associated with an improved local DFS. Adjuvant radiotherapy (p = 0.011) was also independently associated with an improved overall DFS.
This study demonstrated that that local disease failure was still a considerable clinical problem following complete EPP. The data also showed that patients with epithelial histology and receiving adjuvant radiotherapy were associated with an improved disease control.
PMCID: PMC3256490  PMID: 22262998
pleural mesothelioma; extrapleural pneumonectomy; radiotherapy
5.  The influence of socio-economic and surveillance characteristics on breast cancer survival: a French population-based study 
British Journal of Cancer  2008;98(1):217-224.
Survival data on female invasive breast cancer with 9-year follow-up from five French cancer registries were analysed by logistic regression for prognostic factors of cancer stage. The Kaplan–Meier method and log-rank test were used to estimate and compare the overall survival probability at 5 and 7 years, and at the endpoint. The Cox regression model was used for multivariate analysis. County of residence, age group, occupational status, mammographic surveillance, gynaecological prevention consultations and the diagnosis mammography, whether within a screening framework or not, were independent prognostic factors of survival. Moreover, for the same age group, and only for cancers T2 and/or N+ (whether 1, 2 or 3) and M0, the prognosis was significantly better when the diagnosis mammography was done within the framework of screening. Socio-economic and surveillance characteristics are independent prognostic factors of both breast cancer stage at diagnosis and of survival. Screening mammography is an independent prognostic factor of survival.
PMCID: PMC2359707  PMID: 18182980
breast neoplasm; mammography; mass screening; survival analysis; socio-economic factors
6.  Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma 
To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma (MGC) and signet-ring cell carcinoma (SRCC).
Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery, Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed. The clinicopathological features were analyzed statistically using χ2 test. Survival was analyzed using the Kaplan-Meier method and multivariate analysis of Cox proportional hazards regression model (backward, stepwise).
A total of 181 patients with gastric cancer (74 MGC, 107 SRCC) were included. MGC, when compared with SRCC, was featured by senile patients, stage III and IV, upper third stomach, large tumor size, positive lymph node metastasis, and positive lymphatic vascular invasion (P<0.05). The overall 5-year survival rate showed no difference between the two groups (48.8% vs. 44.8%, P>0.05). However, the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age <60 years, negative distant metastasis, and tumor localized at upper third stomach (P<0.05). Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group, and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group.
While compared with SRCC, MGC is associated with a more aggressive tumor biologic behavior. There is no statistically significant difference in distant metastasis, an independent prognostic indicator for both MGC and SRCC, which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.
PMCID: PMC3555291  PMID: 23372339
Mucinous gastric carcinoma; signet-ring cell carcinoma; clinicopathology; prognosis
7.  FAM70B as a Novel Prognostic Marker for Cancer Progression and Cancer-Specific Death in Muscle-Invasive Bladder Cancer 
Korean Journal of Urology  2012;53(9):598-606.
To validate whether FAM70B, which was found in our micro-array profiling as a prognostic marker for cancer survival, could accurately predict prognosis in patients with muscle-invasive bladder cancer (MIBC).
Materials and Methods
A total of 124 patients with MIBC were enrolled in this study. The FAM70B expression level was analyzed by real-time polymerase chain reaction by using RNA from tumor tissues. The prognostic effect of FAM70B was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model.
Kaplan-Meier estimates showed a significant difference in progression-free survival (log-rank test, p=0.011) and cancer-specific survival (log-rank test, p=0.017) according to FAM70B gene expression level. By multivariate Cox regression analysis, high FAM70B expression was predictive of cancer progression (hazard ratio [HR], 2.115, p=0.013) and cancer-specific death (HR, 1.925; p=0.033). In the subgroup analysis, high expression of FAM70B was associated with poor cancer-specific survival, progression-free survival, and overall survival in the patients who underwent cystectomy (log-rank test, p=0.013, p=0.036, p=0.005, respectively). In the chemotherapy group, FAM70B expression was associated with cancer-specific survival and progression-free survival (log-rank test, p=0.013, p=0.042, respectively). Moreover, high FAM70B expression was associated with shorter cancer-specific survival in localized or locally advanced tumor stages (log-rank test, p=0.016).
We confirmed the significance of FAM70B as a prognostic marker in a validation cohort. Therefore, we propose that the FAM70B gene could be used to more precisely predict cancer progression and cancer-specific death in patients with MIBC.
PMCID: PMC3460001  PMID: 23060996
Bladder cancer; Gene expression profiling; Micro-array; Prognosis
8.  Prognostic factors of overall survival in renal cancer patients – single oncological center study 
The clinical course of renal cancer remains difficult to predict. Attempts to appoint new independent prognostic factors (IPFs) and comparisons of already identified ones among populations are inevitable to develop more effective prognostic instruments. The aim of this study was to evaluate IPFs of overall survival in a given population of patients with renal cancer.
Materials and methods
Retrospective analysis of 148 patients with renal cancer treated at the Oncological Institute in Cracow from 2000 to 2007 was performed. Mean follow–up was 51 months. Using the log–rang test, a group of clinicopathological and biochemical features was analyzed in respect to their influence on overall survival. Results were presented as Kaplan–Meier curves. Final identification of IPFs was made by multivariate Cox regression analysis.
Overall survival rate at 1, 2, and 5–year follow–up was 58.8%, 38.2%, and 21.4%, respectively. The set of identified IPFs consisted of performance status, smoking history, hemoglobin concentration, anatomical staging, tumor grade, and the presence of microvascular invasion. It was confirmed that only nephrectomy increases significantly overall survival.
Apart from smoking history, the role of all other IPFs identified in our study is well documented in the literature. Smoking history seems to be a new IPF with strong negative impact on survival in patients with RCC.
PMCID: PMC3974466
prognostic factors; renal cancer; population study; overall survival
9.  Small bowel carcinoid: Location isn’t everything! 
AIM: To investigate the prognostic significance of the primary site of disease for small bowel carcinoid (SBC) using a population-based analysis.
METHODS: The Surveillance, Epidemiology and End Results (SEER) database was queried for histologically confirmed SBC between the years 1988 and 2009. Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan-Meier method and compared using Log rank testing. Log rank and multivariate Cox regression analyses were used to identify predictors of survival using age, year of diagnosis, race, gender, tumor histology/size/location, tumor-node-metastasis stage, number of lymph nodes (LNs) examined and percent of LNs with metastases.
RESULTS: Of the 3763 patients, 51.2% were male with a mean age of 62.13 years. Median follow-up was 50 mo. The 10-year OS and DSS for duodenal primaries were significantly better when compared to jejunal and ileal primaries (P = 0.02 and < 0.0001, respectively). On multivariate Cox regression analysis, after adjusting for multiple factors, primary site location was not a significant predictor of survival (P = 0.752 for OS and P = 0.966 DSS) while age, number of primaries, number of LNs examined, T-stage and M-stage were independent predictors of survival.
CONCLUSION: This 21-year, population-based study of SBC challenges the concept that location of the primary lesion alone is a significant predictor of survival.
PMCID: PMC3753437  PMID: 23983905
Small bowel carcinoid; Primary tumor location; Survival; Prognosis; National Comprehensive Cancer network guidelines
10.  High density of peritumoral lymphatic vessels is a potential prognostic marker of endometrial carcinoma: a clinical immunohistochemical method study 
BMC Cancer  2010;10:131.
The lymphatic system is a major route for cancer cell dissemination and also a potential target for antitumor therapy. To investigate whether increased lymphatic vessel density (LVD) is a prognostic factor for nodal metastasis and survival, we studied peritumoral LVD (P-LVD) and intratumoral LVD (I-LVD) in samples from 102 patients with endometrial carcinoma;
Endometrial carcinoma tissues were analyzed for lymphatic vessels by immunohistochemical staining with an antibody against LYVE-1. Univariate analysis was performed with Kaplan-Meier life-table curves to estimate survival, and was compared using the log rank test. Prognostic models used multivariate Cox regression analysis for multivariate analyses of survival;
Our study showed that P-LVD, but not I-LVD, was significantly correlated with lymph vascular space invasion (LVSI), lymph node metastasis, tumor stage, and CD44 expression in endometrial carcinoma. Moreover, P-LVD was an independent prognostic factor for progression-free survival and overall survival of endometrial carcinoma;
P-LVD may serve as a prognostic factor for endometrial carcinoma. The peritumoral lymphatics might play an important role in lymphatic vessel metastasis.
PMCID: PMC2858111  PMID: 20374665
11.  Expression of FOXO1 is associated with GATA3 and Annexin-1 and predicts disease-free survival in breast cancer 
To determine the prognostic value of FOXO1, GATA3 and Annexin-1 expression in breast cancer.
Tissue microarray and individual paraffin tissue slides from 131 patients were used for the study. The association of FOXO1, GATA3 and Annexin-1 expression with clinicopathological features of breast cancer and disease outcome was examined in retrospective samples. Kaplan-Meier survival curves and Cox regression with multivariate analysis were used for assessing the relative risk (RR) and disease-free survival (DFS). The expression of FOXO1, GATA3 and Annexin-1 were determined by immunohistochemistry and the association among the three proteins was analyzed by Logistic regression analysis.
The nuclear expression of FOXO1 was observed in most of the normal breast tissues and 51.3% of the malignant breast tissues. GATA3 and Annexin-1 were expressed at 73% and 24.6% respectively in breast cancer tissues. The expression of FOXO1, GATA3 and Annexin-1 were all inversely correlated with lymph node-positive tumors. Both FOXO1 and Annexin-1 expression were also inversely associated with HER2-overexpressing tumors. FOXO1 expression was significantly associated with both GATA3 and Annexin-1 expression. In addition, Multivariate analyses confirm that only FOXO1 levels independently predict DFS.
FOXO1 expression in breast cancer is regulated by the PI3K/Akt pathway. The expression of FOXO1 is also associated with GATA3 and/or Annexin-1. Restoring or targeting FOXO1 to the cell nucleus in breast cancer tissues may improve response to therapy and disease outcome. Further clinical studies are warranted to test this hypothesis.
PMCID: PMC3236574  PMID: 22206049
FOXO1; GATA3; annexin-1; survival; breast cancer
12.  Prognostic factors of T4 gastric cancer patients undergoing potentially curative resection 
AIM: To investigate the prognostic factors of T4 gastric cancer patients without distant metastasis who could undergo potentially curative resection.
METHODS: We retrospectively analyzed the clinical data of 71 consecutive patients diagnosed with T4 gastric cancer and who underwent curative gastrectomy at our institutions. The clinicopathological factors that could be associated with overall survival were evaluated. The cumulative survival was determined by the Kaplan-Meier method, and univariate comparisons between the groups were performed using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard model and a step-wise procedure.
RESULTS: The study patients comprised 53 men (74.6%) and 18 women (25.4%) aged 39-89 years (mean, 68.9 years). Nineteen patients (26.8%) had postoperative morbidity: pancreatic fistula developed in 6 patients (8.5%) and was the most frequent complication, followed by anastomosis stricture in 5 patients (7.0%). During the follow-up period, 28 patients (39.4%) died because of gastric cancer recurrence, and 3 (4.2%) died because of another disease or accident. For all patients, the estimated overall survival was 34.1% at 5 years. Univariate analyses identified the following statistically significant prognostic factors in T4 gastric cancer patients who underwent potentially curative resection: peritoneal washing cytology (P < 0.01), number of metastatic lymph nodes (P < 0.05), and venous invasion (P < 0.05). In multivariate analyses, only peritoneal washing cytology was identified as an independent prognostic factor (HR = 3.62, 95% CI = 1.37-9.57) for long-term survival.
CONCLUSION: Positive peritoneal washing cytology was the only independent poor prognostic factor for T4 gastric cancer patients who could be treated with potentially curative resection.
PMCID: PMC3063911  PMID: 21448423
Gastric cancer; T4; Prognostic factors; Peritoneal cytology; Venous invasion
13.  Yes-Associated Protein Is an Independent Prognostic Marker in Hepatocellular Carcinoma 
Cancer  2009;115(19):4576-4585.
Yes-associated protein (YAP), a downstream target of the Hippo signaling pathway, was recently linked to hepatocarcinogenesis in a mouse hepatocellular carcinoma (HCC) model. The objective of the current study was to investigate the clinical significance of YAP in HCC and its prognostic values in predicting survival and tumor recurrence.
The authors collected 177 pairs of tumor and adjacent nontumor tissue from HCC patients with definitive clinicopathologic and follow-up data. YAP expression was determined by immunohistochemistry, Western blot analysis, and quantitative polymerase chain reaction. Association of YAP with each clinicopathologic feature was analyzed by Pearson chi-square test, and HCC-specific disease-free survival and overall survival by Kaplan-Meier curves and log-rank test. Multivariate Cox regression analyses of YAP in HCC were also performed.
YAP was expressed in the majority of HCC cases (approximately 62%) and mainly accumulated in the tumor nucleus. Overexpression of YAP in HCC was significantly associated with poorer tumor differentiation (Edmonson grade; P = .021) and high serum α-fetoprotein (AFP) level (P < .001). Kaplan-Meier and Cox regression data indicated that YAP was an independent predictor for HCC-specific disease-free survival (hazards ratio [HR], 1.653; 95% confidence interval [95% CI], 1.081-2.528 [P = .02]) and overall survival (HR, 2.148; 95% CI, 1.255-3.677 [P = .005]).
YAP is an independent prognostic marker for overall survival and disease-free survival times of HCC patients and clinicopathologically associated with tumor differentiation and serum AFP level. It is a potential therapeutic target for this aggressive malignancy.
PMCID: PMC2811690  PMID: 19551889
hepatocellular carcinoma; hippo signaling; prognostic marker; tumor recurrence; Yes-associated protein
14.  Clinical characteristics and prognostic analysis of triple-negative breast cancer patients 
Molecular and Clinical Oncology  2013;2(2):245-251.
It is well-established that triple-negative breast cancer (TNBC) is a subtype of breast cancer, characterized by a poor prognosis and aggressive biological behavior. However, the available relevant data on TNBC in non-Western populations are limited. In order to analyze the clinicopathological and molecular biological characteristics and observe survival and prognostic factors, 972 breast cancer patients (156 of whom had TNBC) who received treatment at the First Affiliated Hospital of Medical School of Xi'an Jiaotong University and the First Hospital of China Medical University, between January, 2004 and January, 2007 were retrospectively evaluated. In the univariate analysis, tumor size, TNM stage, axillary lymph node status and recurrence or metastasis were identified as prognostic factors for 7-year disease-free survival (DFS) and overall survival (OS). Our multivariate Cox's regression analysis demonstrated that tumor size and axillary lymph node status were significant prognostic factors for 7-year DFS and OS. Notably, tumor subgroup (TNBC vs. non-TNBC) was a significant prognostic factor associated with 7-year DFS and OS in breast cancer. It was suggested that TNBC exhibited a worse 7-year survival compared with that in non-TNBC patients, most likely due to its more aggressive behavior and insensitivity to specific therapy.
PMCID: PMC3917786  PMID: 24649341
clinicopathological characteristics; prognostic analysis; survival analysis; triple-negative breast cancer
15.  Clinicopathologic characteristics and prognostic factors of 63 gastric cancer patients with metachronous ovarian metastasis 
Cancer Biology & Medicine  2013;10(2):86-91.
This study aims to explore the clinicopathologic characteristics and prognostic factors of gastric cancer patients with metachronous ovarian metastasis.
Clinicopathologic data were collected from 63 post-operative gastric cancer patients with metachronous ovarian metastasis. The patients were admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College between January 1999 and December 2011. A log-rank test was conducted for survival analysis. Possible prognostic factors that affect survival were examined by univariate analysis. A Cox regression model was used for multivariate analysis.
The incidence of ovarian metastasis was 3.4% with a mean age of 45 years. Up to 65.1% of the patients were pre-menopausal. The mean interval between ovarian metastasis and primary cancer was 16 months. Lowly differentiated carcinoma ranked first in the primary gastric cancers. The majority of lesions occurred in the serous membrane (87.3%). The metastatic sites included N2-3 lymph nodes (68.3%), bilateral ovaries (85.7%), and peritoneal membrane (73%). Total resection of metastatic sites was performed (31.7%). The overall median survival was 13.6 months, whereas the overall 1-, 2-, and 3-year survival rates were 52.5%, 22.0%, and 9.8%, respectively. The 5-year survival rate was zero. Univariate analysis showed that the patient prognosis was correlated with metastatic peritoneal seeding, vascular tumor embolus, range of lesion excision, and mode of comprehensive treatment with adjuvant chemotherapy (P<0.05). Multivariate analysis indicated that metastatic peritoneal seeding was an independent prognostic factor for gastric cancer patients with ovarian metastasis (P<0.01).
Effective control of peritoneal seeding—induced metastasis is important for improving the prognosis of gastric cancer patients with ovarian metastasis.
PMCID: PMC3719191  PMID: 23882423
Gastric neoplasms; ovary; metastasis; prognosis
16.  Prognostic factors for 5-year survival after local excision of rectal cancer 
AIM: To evaluate the prognostic factors for 5-year survival after local excision of rectal cancer, and to examine the therapeutic efficacy and surgical indications for this procedure.
METHODS: Clinical data, obtained from 106 local rectal cancer excisions performed between January 1980 and December 2005, were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier method, statistical comparisons were performed using the log-rank test, and multivariate analysis was performed using the Cox proportional hazards model.
RESULTS: Transanal, transsacral, and transvaginal excisions were performed in 92, 12, and 2 cases, respectively. The rate of complication, local recurrence, and 5-year survival was 6.6%, 17.0%, and 86.7%, respectively. Univariate analysis showed that T stage, vascular invasion, and local recurrence were related to the prognosis of the cases (P < 0.05). Multivariate analysis showed that T stage [P = 0.011, 95% confidence interval (CI) = 1.194-3.878] and local recurrence (P = 0.022, 95% CI = 1.194-10.160) were the major prognostic factors for 5-year survival of cases after local excision of rectal cancer.
CONCLUSION: Local rectal cancer excision is associated with few complications, and suitable for stages Tis and T1 rectal cancer. Prevention of local recurrence, active postoperative follow-up, and administration of salvage therapy are the effective methods to increase the efficacy of local excision of rectal cancer.
PMCID: PMC2658846  PMID: 19291825
Rectal cancer; Surgery; Local excision; Recurrence; Prognosis
17.  High expression level of EDIL3 in HCC predicts poor prognosis of HCC patients 
AIM: To determine the role of epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) in pathogenesis of hepatocellular carcinoma (HCC) by investigating the EDIL3 expression in HCC and its prognostic value for HCC.
METHODS: EDIL3 expression was detected in 101 HCC surgical tissue samples with immunohistochemistry method, and its relation with clinicopathologic features and prognosis of HCC patients was analyzed.
RESULTS: EDIL3 was highly expressed in 48.5% of the HCC patients. Although the EDIL3 expression level did not correlate with any clinicopathological parameters, Kaplan-Meier survival analysis showed that high expression level of EDIL3 resulted in a significantly poor prognosis of HCC patients (log-rank test, P = 0.010). Multivariate Cox’s analysis showed that the EDIL3 expression level was a significant and independent prognostic parameter for the overall survival rate of HCC patients (hazard ratio = 1.978, 95% confidence interval = 1.139-3.435, P = 0.015).
CONCLUSION: High expression level of EDIL3 predicts poor prognosis of HCC patients. EDIL3 may be a potential target of antiangiogenic therapy for HCC.
PMCID: PMC2945496  PMID: 20857535
Epidermal growth factor-like repeats and discoidin I-like domains 3; Hepatocellular carcinoma; Prognosis; Angiogenesis
18.  Survival of Male Breast Cancer in Fars, South of Iran 
Although breast cancer in men is uncommon, its incidence rate has an increasing trend. Due to its low incidence, there are few studies in this subject and limited information is available. The purpose of this study was to investigate clinicopathological characteristics and survival of male breast cancer (MBC) in Fars Province, south of Iran.
The data for this study were obtained from the population based cancer registry of Vice-Chancellor for Health Affairs of Shiraz University of Medical Sciences and Shiraz hospitals between January 1, 1989 and January 1, 2008, including 64 patients with MBC. Demographic, clinical and pathological aspects were investigated. The Kaplan-Meier method was used for the determination of survival rate and Log Rank test for the comparison. The Cox proportional hazards model was used for the multiple analysis.
The patients’ mean age at the time of diagnosis was 60.3 years (SD=12.7). The most frequent age group (26.6%) was 51-60 years. The most common symptom (96.8%) was a palpable mass. The majority of patients (44.4%) had a symptom duration of less than or equal to 6 months. 56.3% of the patients had a tumor size of 2-4.9 cm. Forty six percent of the cases had axillary lymph node involvement. The median survival time was 10.0 years [95% confidence interval (CI): 6.0-14.0]. The 5 year overall survival rate was 66.0% (95% CI=51.0-81.0%). The median survival time of patients with axillary lymph node involvement was 8.2 years (95% CI=6.7-9.6) and for the cases without involvement was 12.0 years (95% CI=8.4-15.2). In addition to axillary lymph node involvement, positive family history in contrast to negative family history and left tumors in compari-son with right tumors were poorer prognostic factors in univariate analysis respectively (p=0.006, p=0.031). In multiple analysis, axillary lymph node involvement was an independent predictor of poorer survival (Hazard ratio=1.6, 95% CI=1.1-6.4, p=0.030) and the other variables did not have a significant effect.
The mean age of MBC in this series is lower than that in western countries. It is compatible to the mean age of female breast cancer which is approximately one decade less than that in developed countries. The survival rate of MBC is relatively lower than that in western countries. Axillary lymph node involvement is an important prognostic factor in the survival of MBC. Multicenter population based studies with greater number of patients are required for better estimation of different aspects of MBC in Iran.
PMCID: PMC3371920  PMID: 22737442
Breast cancer; Male; Survival; Iran
19.  Barriers to adequate follow-up during adjuvant therapy may be important factors in the worse outcome for Black women after breast cancer treatment 
Black women appear to have worse outcome after diagnosis and treatment of breast cancer. It is still unclear if this is because Black race is more often associated with known negative prognostic indicators or if it is an independent prognostic factor. To study this, we analyzed a patient cohort from an urban university medical center where these women made up the majority of the patient population.
We used retrospective analysis of a prospectively collected database of breast cancer patients seen from May 1999 to June 2006. Time to recurrence and survival were analyzed using the Kaplan-Meier method, with statistical analysis by chi-square, log rank testing, and the Cox regression model.
265 female patients were diagnosed with breast cancer during the time period. Fifty patients (19%) had pure DCIS and 215 patients (81%) had invasive disease. Racial and ethnic composition of the entire cohort was as follows: Black (N = 150, 56.6%), Hispanic (N = 83, 31.3%), Caucasian (N = 26, 9.8%), Asian (N = 4, 1.5%), and Arabic (N = 2, 0.8%). For patients with invasive disease, independent predictors of poor disease-free survival included tumor size, node-positivity, incompletion of adjuvant therapy, and Black race. Tumor size, node-positivity, and Black race were independently associated with disease-specific overall survival.
Worse outcome among Black women appears to be independent of the usual predictors of survival. Further investigation is necessary to identify the cause of this survival disparity. Barriers to completion of standard post-operative treatment regimens may be especially important in this regard.
PMCID: PMC2277417  PMID: 18298840
20.  Lymph node ratio and preoperative CA 19-9 levels predict overall survival and recurrence-free survival in patients with resected pancreatic adenocarcinoma 
AIM: Clinicopathologic factors predicting overall survival (OS) would help identify a subset to benefit from adjuvant therapy.
METHODS: One hundred and sixty-nine patients patients from 1984 to 2009 with curative resections for pancreatic adenocarcinoma were included. Tumors were staged by American Joint Committee on Cancer 7th edition criteria. Univariate and multivariable analyses were performed using Kaplan-Meier methodology or Cox proportional hazard models. Log-rank tests were performed. Statistical inferences were assessed by two-sided 5% significance level.
RESULTS: Median age was 67.1 (57.2-73.0) years with equal gender distribution. Tumors were in the head (89.3%) or body/tail (10.7%). On univariate analysis, adjuvant therapy, lymph node (LN) ratio, histologic grade, negative margin status, absence of peripancreatic extension, and T stage were associated with improved OS. Adjuvant therapy, LN ratio, histologic grade, number of nodes examined, negative LN status, and absence of peripancreatic extension were associated with improved recurrence-free survival (RFS). On multivariable analysis, LN ratio and carbohydrate antigen (CA) 19-9 levels were associated with OS. LN ratio was associated with RFS.
CONCLUSION: The LN ratio and CA 19-9 levels are independent prognostic factors following curative resections of pancreatic cancer.
PMCID: PMC3581835  PMID: 23444312
Pancreatic adenocarcinoma; Lymph node ratio; Carbohydrate antigen 19-9; Recurrence-free survival; Overall survival
21.  Pretreatment Thrombocytosis as a Prognostic Factor in Metastatic Breast Cancer 
Background. An elevated platelet count is often associated with malignancies, and it has been confirmed as an adverse prognostic factor in various cancers including early stage breast cancer. We sought to determine if thrombocytosis is also a prognostic factor in metastatic breast cancer. Patients and Methods. The records of 165 metastatic breast cancer patients with complete follow-up that had thrombocytosis or normal platelet counts were reviewed. Kaplan-Meier curves were constructed, and the survivals of the two groups were compared using the LogRank test. A Cox regression analysis was used to determine if thrombocytosis is an independent factor for overall and progression free survival. Results. There was a statistically significant difference in overall and progression free survival favoring the normal platelets group (LogRank test P = 0.038 and 0.008, resp.). Thrombocytosis remained a significant adverse prognostic factor in multivariate analysis. Other independent prognostic factors for overall survival included age, ER/PR status, and grade. Conclusion. Thrombocytosis represents an independent adverse prognostic factor in patients with metastatic breast cancer. Thus metastatic breast cancer joins a range of cancers in which this easily measurable value can be used for clinical prognostication. Further use as a predictive value for specific treatments has a rationale and deserves to be investigated.
PMCID: PMC3707237  PMID: 23864954
22.  Prediction of outcomes for patients with brain parenchymal metastases from breast cancer (BC): a new BC-specific prognostic model and a nomogram 
Neuro-Oncology  2012;14(8):1105-1113.
The purpose of this study is to validate the recently published Breast–Graded Prognostic Assessment (GPA) and propose a new prognostic model and nomogram for patients with brain parenchymal metastases (BM) from breast cancer (BC). We retrospectively investigated 171 consecutive patients who received a diagnosis of BM from BC during 2000–2008. We appraised the recently proposed Sperduto's BC-specific GPA in training cohort through Kaplan-Meier survival curve using log-rank test and area under the curve for the BC-GPA predicting overall survival at 1 year and developed a new nomogram to predict outcomes using multivariate Cox-regression analysis. By putting the Sperduto's Breast-GPA together with our nomogram, we developed a new prognostic model. We validated our new prognostic model with an independent external patient cohort from 2 institutes for the same period. On the basis of our Cox-regression analysis, therapeutic effect of trastuzumab and status of extracranial systemic disease control were incorporated into our new prognostic model in addition to Karnofsky performance status, age, and hormonal status. Our new prognostic model showed significant discrimination in median survival time, with 3.7 months for class I (n = 15), 7.8 months for class II (n = 82), 10.7 months for class III (n = 42), and 19.2 months for class IV (n = 32; P < .0001). The new prognostic model accurately predicted survival among patients with BC from BM in an external validation cohort (P < .0001). We propose a new prognostic model and a nomogram reflecting the different biological features of BC, including treatment effect and status of extracranial disease control, which was excellently validated in an independent external cohort.
PMCID: PMC3408262  PMID: 22693244
brain metastasis; breast cancer; HER2; prognosis; trastuzumab
23.  Blood neutrophil-lymphocyte ratio predicts survival for stages III-IV gastric cancer treated with neoadjuvant chemotherapy 
Accurate predictors of survival for patients with advanced gastric cancer treated with neoadjuvant chemotherapy are currently lacking. In this study, we aimed to evaluate the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with stage III-IV gastric cancer who received neoadjuvant chemotherapy.
We enrolled 46 patients in this study. The NLR was divided into two groups: high (>2.5) and low (≤2.5). Univariate analysis on progression-free survival (PFS) and overall survival(OS) was performed using the Kaplan-Meier and log-rank tests, and multivariate analysis was conducted using the Cox proportional hazards regression model. We analyzed whether chemotherapy normalized high NLR or not, and evaluated the prognostic significance of normalization on survival.
The univariate analysis showed that PFS and OS were both worse for patients with high NLR than for those with low NLR before chemotherapy (median PFS 16 and 49 months, respectively, P = 0.012; median OS 21 and 52 months, P = 0.113). PFS and OS were also worse for patients with high NLR than for those with low NLR before surgery (median PFS 12 and 35 months, P = 0.019; median OS 21 and 52 months, P = 0.082). Multivariate analysis showed that both NLR before chemotherapy and surgery were independent prognostic factors of PFS. Neoadjuvant chemotherapy normalized high NLR in 11 of 24 patients, and these 11 patients had better median PFS and OS than the 13 patients who had high NLR both before chemotherapy and before surgery (PFS: 35.0 and 10.0 months, P = 0.003; OS: 60 and 16 months, P = 0.042).
NLR may serve as a potential biomarker for survival prognosis in patients with stage III-IV gastric cancer receiving neoadjuvant chemotherapy.
PMCID: PMC3665689  PMID: 23705622
Gastric cancer; Neutrophil-lymphocyte ratio; Univariate analysis; Multivariate analysis; Prognosis
24.  Postmastectomy locoregional recurrence and recurrence-free survival in breast cancer patients 
One essential outcome after breast cancer treatment is recurrence of the disease. Treatment decision is based on assessment of prognostic factors of breast cancer recurrence. This study was to investigate the prognostic factors for postmastectomy locoregional recurrence (LRR) and survival in those patients.
114 patients undergoing mastectomy and adjuvant radiotherapy in Cancer Institute of Tehran University of Medical Sciences were retrospectively reviewed between 1996 and 2008. All cases were followed up after initial treatment of patients with breast cancer via regular visit (annually) for discovering the LRR. Cumulative recurrence free survival (RFS) was determined using the Kaplan-Meier method, with univariate comparisons between groups through the log-rank test. The Cox proportional hazards model was used for multivariate analysis.
The median follow up time was 84 months (range 2-140). Twenty-three (20.2%) patients developed LRR. Cumulative RFS rate at 2.5 years and 5 years were 86% (95%CI, 81-91) and 82.5% (95%CI, 77-87) respectively. Mean RFS was 116.50 ± 4.43 months (range, 107.82 - 125.12 months, 95%CI). At univariate and multivariate analysis, factors had not any influence on the LRR.
Despite use of adjuvant therapies during the study, we found a LRR rate after mastectomy of 20.2%. Therefore, for patients with LRR without evidence of distant disease, aggressive multimodality therapy is warranted.
PMCID: PMC2868847  PMID: 20398406
25.  High mobility group-box 3 overexpression is associated with poor prognosis of resected gastric adenocarcinoma 
AIM: To elucidate high mobility group-box 3 (HMGB3) protein expression in gastric adenocarcinoma, its potential prognostic relevance, and possible mechanism of action.
METHODS: Ninety-two patients with gastric adenocarcinomas surgically removed entered the study. HMGB3 expression was determined by immunohistochemistry through a tissue microarray procedure. The clinicopathologic characteristics of all patients were recorded, and regular follow-up was made for all patients. The inter-relationship of HMGB3 expression with histological and clinical factors was analyzed using nonparametric tests. Survival analysis was carried out by Kaplan-Meier (log-rank) and multivariate Cox (Forward LR) analyses between the group with overexpression of HMGB3 and the group with low or no HMGB3 expression to determine the prognosis value of HMGB3 expression on overall survival. Further, HMGB3 expression was knocked down by small hairpin RNAs (shRNAs) in the human gastric cancer cell line BGC823 to observe its influence on cell biological characteristics. The MTT method was utilized to detect gastric cancer cell proliferation changes, and cell cycle distribution was analyzed by flow cytometry.
RESULTS: Among 92 patients with gastric adenocarcinomas surgically removed in this study, high HMGB3 protein expression was detected in the gastric adenocarcinoma tissues vs peritumoral tissues (P < 0.001). Further correlation analysis with patients’ clinical and histology variables revealed that HMGB3 overexpression was obviously associated with extensive wall penetration (P = 0.005), a positive nodal status (P = 0.004), and advanced tumor-node-metastasis (TNM) stage (P = 0.001). But there was no correlation between HMGB3 overexpression and the age and gender of the patient, tumor localization or histologic grade. Statistical Kaplan-Meier survival analysis disclosed significant differences in overall survival between the HMGB3 overexpression group and the HMGB3 no or low expression group (P = 0.006). The expected overall survival time was 31.00 ± 3.773 mo (95%CI = 23.605-38.395) for patients with HMGB3 overexpression and 49.074 ± 3.648 mo (95%CI = 41.925-57.311) for patients with HMGB3 no and low-level expression. Additionally, older age (P = 0.040), extensive wall penetration (P = 0.008), positive lymph node metastasis (P = 0.005), and advanced TNM tumor stage (P = 0.007) showed negative correlation with overall survival. Multivariate Cox regression analysis indicated that HMGB3 overexpression was an independent variable with respect to age, gender, histologic grade, extent of wall penetration, lymph nodal metastasis, and TNM stage for patients with resectable gastric adenocarcinomas with poor prognosis (hazard ratio = 2.791, 95%CI = 1.233-6.319, P = 0.019). In the gene function study, after HMGB3 was knocked down in the gastric cell line BGC823 by shRNA, the cell proliferation rate was reduced at 24 h, 48 h and 72 h. Compared to BGC823 shRNA-negative control (NC) cells, the cell proliferation rate in cells that had HMGB3 shRNA transfected was significantly decreased (P < 0.01). Finally, cell cycle analysis by FACS showed that BGC823 cells that had HMGB3 knocked down were blocked in G1/G0 phase. The percentage of cells in G1/G0 phase in BGC823 cells with shRNA-NC and with shRNA-HMGB3 was 46.84% ± 1.7%, and 73.03% ± 3.51% respectively (P = 0.001), whereas G2/M cells percentage decreased from 26.51% ± 0.83% to 17.8% ± 2.26%.
CONCLUSION: HMGB3 is likely to be a useful prognostic marker involved in gastric cancer disease onset and progression by regulating the cell cycle.
PMCID: PMC3544037  PMID: 23326140
High mobility group-box 3; Gastric adenocarcinoma; Prognosis; Cell proliferation; Cell cycle

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