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1.  Clinicopathological features and treatment sensitivity of elderly Chinese breast cancer patients 
Oncology Letters  2010;1(6):1037-1043.
This study aimed to determine the clinicopathological features and treatment sensitivity of elderly breast cancer patients in China. The clinical data of 594 elderly breast cancer patients of 70 or more years of age were collected and compared to those of 657 patients of less than 70 years of age to analyze whether breast cancer in the elderly is different and whether the difference affected outcome. The median age was 75.2 years in the elderly patients and 49.8 years in the young patients. Age of menarche, parous status and body mass index were similar in the two groups. A higher frequency of steroid receptor-positive rate, a lower expression of HER-2 and p53, less axillary node-positive rate and earlier tumor stage were found in patients of 70 years or older. The 5-year relapse-free survival (RFS) and overall survival (OS) was 77 and 82% in the elderly and 86 and 93% in the young patients, respectively. Patients with estrogen receptor (ER)-positive or lymph node (LN)-negative cancers showed a more favorable outcome in the elderly patients. RFS and OS were increased in elderly patients who underwent endocrine therapy or omitted chemotherapy. Breast cancer in the elderly had more favorable tumor features, using estrogen receptor and lymph node status as prognostic factors. It was therefore concluded that adjuvant endocrine therapy may benefit elderly patients, while chemotherapy may not.
PMCID: PMC3412465  PMID: 22870109
breast cancer; elderly patients; prognostic factor; survival
2.  Taekwondo Techniques and Competition Characteristics Involved in Time-Loss Injuries 
Journal of Sports Science & Medicine  2007;6(CSSI-2):45-51.
The purpose of this study was to assess time-loss injuries in young and adult taekwondo athletes. Participants were 2739 children (11-13 years), Junior (14-17 years) and adult males and females (18 years and older) competing in the national Greek championships. Injury data were collected by project staff with all diagnoses made by the tournament physician. Odds ratios were computed as well as 95% confidence intervals around the injury rates. The female Juniors had a higher time-loss injury rate (Fisher’s Exact Test p = 0.033) than their adult counterparts. However, they were not at a higher risk of incurring a time-loss injury: OR = 0.143, 95% CI: 0.018-1.124. Collapsed over age, the females as a group recorded more time-loss injuries [11.36/1,000 A-E (95% CI: 6.25-16.47) versus 7.40/1,000 A-E (95% CI: 4.44-10.36)], but this was not significant (OR = 0.703, 95% CI: 0.383-1.293). In the Juniors, the boys only incurred time-loss injuries to the head and neck. There was no difference in the Junior girls in the distribution of time-loss injuries across body region, although they were at higher risk of sustaining an injury to the head and neck (OR = 1.510, 95% CI: 0.422-5.402) but this was not statistically significant. Although there were no statistical differences among age groups within gender, the Junior boys and girls (11-13 years) sustained more cerebral concussions. The Junior boys were at a higher risk of incurring a cerebral concussion than the boys (OR = 7.871, 95% CI: 0.917-67.583, Fisher’s Exact Test p = 0.036). In the males, there was no difference between the men and Junior boys in injury rate for swing kicks compared to other techniques (OR = 2.000, 95% CI = 0.397-28.416). There also was no difference between the men and boys (OR = 4.800, 95% CI: 0.141-58.013). To help reduce the incidence of time-loss injuries in taekwondo, especially cerebral concussions, it is suggested for coaches to emphasize blocking skills. Educating referees, coaches and athletes plays an important role in helping to reduce taekwondo time-loss injuries.
Key pointsThe purpose of this study was to assess time-loss injuries in young and adult taekwondo athletes.Collapsed over age, the females as a group recorded more time-loss injuries but this was not significant.The Junior boys were at a higher risk of incurring a cerebral concussion than the boys.To help reduce the incidence of time-loss injuries in taekwondo, especially cerebral concussions, it is suggested for coaches to emphasize blocking skills.Educating referees, coaches and athletes plays an important role in helping to reduce taekwondo time-loss injuries.
PMCID: PMC3809043  PMID: 24198703
Martial arts; taekwondo; time-loss; Greek; injuries
3.  Young age: an independent risk factor for disease-free survival in women with operable breast cancer 
BMC Cancer  2004;4:82.
The incidence of breast cancer in young women (age < 35) is low. The biology of the disease in this age group is poorly understood, and there are conflicting data regarding the prognosis for these women compared to older patients.
We retrospectively analyzed 2040 consecutive primary invasive breast cancer patients who underwent surgical procedures at our institution between 1990 and 1999. The younger age group was defined as patients aged <35 years at the time of diagnosis. The clinicopathological characteristics and treatment outcomes were compared between younger and older age groups.
A total of 256 (12.5%) patients were aged <35. There was a significantly higher incidence of nuclear grade 3 and medullary histological-type tumors in younger patients compared to older patients. Axillary lymph node status, T stage, histological grade, c-erbB2 expression and estrogen receptor status did not differ significantly between the two age groups. Younger patients had a greater probability of recurrence and death at all time periods. Although there was no significant difference in disease-free survival between the two age groups in lymph node-negative patients, the younger group showed worse prognosis among lymph node-positive patients (p < 0.001). In multivariate analysis, young age remained a significant predictor of recurrence (p = 0.010).
Young age (<35) is an independent risk factor for relapse in operable breast cancer patients.
PMCID: PMC545947  PMID: 15546499
4.  Expression and Clinicopathological Significance of CD9 in Gastrointestinal Stromal Tumor 
Journal of Korean Medical Science  2013;28(10):1443-1448.
This study investigated the expression and clinicopathological significance of CD9 in gastrointestinal stromal tumor (GIST). Immunohistochemistry staining for CD9 was performed on tumor tissues from 74 GIST patients. The correlation with clinicopathological features, risk classification and prognosis was analyzed. CD9-positive staining comprised 59.5% (44/74) of the GIST patients. The CD9-positive expression rate of the sample was significantly associated with diameter (P = 0.028), mitotic counts (P = 0.035), risk classification (P = 0.018) and three-year recurrence-free survival (RFS) (P < 0.001). Cox proportional hazards regression (HR = 0.352; P = 0.015) showed that CD9 is an independent factor for post-operative RFS. The subgroup analysis showed that CD9 expression in gastric stromal tumor (GST) is significantly associated with diameter (P = 0.031), risk classification (P = 0.023) and three-year RFS (P = 0.001). The Cox proportional hazards regression (HR = 0.104; P = 0.006) also showed that CD9 is an independent factor for RFS of GST. However, CD9 expression does not have a statistically significant correlation with clinicopathological features, risk classification, and prognosis in non-GST. In conclusion, CD9 expression in GIST appears to be associated with the recurrence and/or metastasis of GIST patients, especially in GST, which may indicate the important role of CD9 in the malignant biological behavior and prognosis of GST.
PMCID: PMC3792597  PMID: 24133347
Gastrointestinal Stromal Tumors; Gastric Stromal Tumor; CD9; Immunohistochemistry; Prognosis
5.  The ectopic expression of BRCA1 is associated with genesis, progression, and prognosis of breast cancer in young patients 
Diagnostic Pathology  2012;7:181.
The study is to explore the histopathological features and the molecular marker expression of young women with breast cancers.
The pathological data of 367 cases of female breast cancer patients were retrospectively analyzed, focusing on the analysis of young breast cancer incidence trends and the clinical and pathological features.
Compared with elderly breast cancer patients, young women with breast cancers had larger tumor sizes, higher histological grades, and lymph node metastasis rates. The majority of patients were in the PTNM III stage, with the clinical and pathological features of strong invasiveness. The positive expression rate of the BRCA1 protein in the young group was higher than that in the old group. BRCA1 expression was positively correlated with the PTNM stage and axillary lymph node metastasis (P < 0.05).
The ectopic expression of BRCA1 is associated with the genesis, progression, and prognosis of young breast cancer patients.
Virtual slides
The virtual slide(s) for this article can be found here:
PMCID: PMC3541118  PMID: 23276146
BRCA1; WWOX; Gene detection
6.  Metaplastic sarcomatoid carcinoma of the breast appears more aggressive than other triple receptor-negative breast cancers 
Breast cancer research and treatment  2011;131(1):10.1007/s10549-011-1393-6.
Metaplastic sarcomatoid carcinoma (MSC) of the breast is usually triple receptor (ER, PR, and HER2) negative and is not currently recognized as being more aggressive than other triple receptor-negative breast cancers. We reviewed archival tissue sections from surgical resection specimens of 47 patients with MSC of the breast and evaluated the association between various clinicopathologic features and patient survival. We also evaluated the clinical outcome of MSC patients compared to a control group of patients with triple receptor-negative invasive breast carcinoma matched for patient age, clinical stage, tumor grade, treatment with chemotherapy, and treatment with radiation therapy. Factors independently associated with decreased disease-free survival among patients with stage I–III MSC of the breast were patient age >50 years (P = 0.029) and the presence of nodal macrometastases (P = 0.003). In early-stage (stage I–II) MSC, decreased disease-free survival was observed for patients with a sarcomatoid component comprising ≥95% of the tumor (P = 0.032), but tumor size was the only independent adverse prognostic factor in early-stage patients (P = 0.043). Compared to a control group of triple receptor-negative patients, patients with stage I–III MSC had decreased disease-free survival (two-sided log rank, P= 0.018). Five-year disease-free survival was 44 ± % versus 74 ± 7% for patients with MSC versus triple receptor-negative breast cancer, respectively. We conclude that MSC of the breast appears more aggressive than other triple receptor-negative breast cancers.
PMCID: PMC3867807  PMID: 21331622
Breast cancer; Metaplastic carcinoma; Sarcomatoid; Triple-negative; Survival
7.  Characteristics and prognosis of gastric cancer in young patients 
Oncology Reports  2013;30(1):43-49.
The clinicopathological features of gastric cancer (GC) differ between younger and older patients, and it is thought that younger patients have a worse prognosis than older patients due to delayed diagnosis and more aggressive tumor behavior. These characteristics, however, remain controversial. A total of 3,818 patients with pathologically confirmed primary gastric adenocarcinoma were treated at our institution. We analyzed the difference in demographic and clinicopathological characteristics between 169 young [≤40 years of age, younger group (YG)] and 3,649 older [>40 years of age, older group (OG)] GC patients. There was a significantly higher proportion of females in the YG compared with the OG (53.3 and 31.0%, respectively; P<0.0001). The 5-year overall survival of the YG was significantly lower compared to that of the OG (59.7 and 65.9%, respectively; P=0.049). However, YG patients with curative resection had a similar 5-year survival rate to OG patients with curative resection (88.0 and 85.8%, respectively; P=0.547). Female patients in the YG showed a significantly lower survival rate than males in the YG (44.3 and 73.1%, respectively; P=0.0002). Multivariate analyses revealed that macroscopic type, depth of invasion, peritoneal metastasis, distant metastasis and curative resection were independent prognostic factors for the YG with GC. Young GC patients who undergo curative resection do not have a worse prognosis than older patients. Early diagnosis is important in successfully carrying out a curative resection and offering a better prognosis, particularly in females.
PMCID: PMC3729235  PMID: 23674196
gastric cancer; prognosis; young; elderly
8.  Prognostic significance of erythropoietin and erythropoietin receptor in gastric adenocarcinoma 
AIM: To investigate the expression of Erythropoietin (Epo) and its receptor (EpoR) in gastric adenocarcinoma (GAC) and the correlation with angiogenesis and clinicopathological features.
METHODS: The expressions of Epo, EpoR and vascular endothelial growth factor (VEGF), as well as microvessel density were evaluated in 172 GAC biopsies by immunohistochemical staining. The correlations between these parameters and patient’s clinicopathological features were analyzed statistically.
RESULTS: The proportion of Epo and EpoR alterations in GAC was higher than that in adjacent normal mucosa (P = 0.035 and 0.030). Epo high-expression was associated with EpoR high-expression, Lauren type, extensive lymph node metastasis and advanced stage of GAC (P = 0.018, 0.018, 0.004 and 0), while EpoR expression was linked with older age, World Health Organization type, extensive lymph node metastasis and advanced stage (P = 0.001, 0.013, 0.008 and 0.001). VEGF high expression was significantly correlated with EpoR low-expression, Lauren type, extensive lymph node metastasis and advanced stage (P = 0.001, 0.001, 0.001 and 0.007). The expression of Epo or EpoR was associated with microvessel density (P = 0.004 and 0.046). On multivariate analysis, only lymph node metastasis, abnormal Epo expression and tumor nodes metastases stage were independently associated with survival. In addition, a strong association with the immunohistochemical expression of EpoR and the angiogenic protein, VEGF, was noted.
CONCLUSION: Increased expression of Epo and EpoR may play a significant role in the carcinogenesis, angiogenesis and progression of GAC. Epo may be an independent prognostic factor.
PMCID: PMC3198023  PMID: 22025882
Erythropoietin; Erythropoietin receptor; Gastric adenocarcinoma; Immunohistochemistry; Prognosis
9.  Being 40 or younger is an independent risk factor for relapse in operable breast cancer patients: The Saudi Arabia experience 
BMC Cancer  2007;7:222.
Breast cancer in young Saudi women is a crucial problem. According to the 2002 annual report of Saudi National Cancer Registry, breast cancers that developed before the age of 40 comprise 26.4% of all female breast cancers comparing to 6.5% in the USA. Breast cancer in young patients is often associated with a poorer prognosis, but there has been a scarcity of published data in the Middle East population.
Total of 867 breast cancer patients seen at King Faisal Specialist Hospital & Research Centre (KFSH&RC) between 1986 and 2002 were reviewed. Patients were divided in two age groups: ≤ 40 years and above 40 years. The clinicopathological characteristics and treatment outcomes were compared between younger and older age groups.
Median age at presentation was 45 years. A total of 288 (33.2%) patients were aged ≤ 40 years. Hormone receptors were positive in 69% of patients 40 and 78.2% of patients above 40 (p = 0.009). There was a significantly higher incidence of grade III tumor in younger patients compared to older patients (p = 0.0006). Stage, tumor size, lymphatic/vascular invasion, number of nodes and axillary lymph node status, did not differ significantly between the two age groups. Younger patients had a greater probability of recurrence at all time periods (p = 0.035). Young age had a negative impact on survival of patients with positive axillary lymph nodes (p = 0.030) but not on survival of patients with negative lymph nodes (p = 0.695). Stage, tumor size, nodal status and hormonal receptors had negative impact on survival. Adjuvant chemotherapy was administered to 87.9% of younger and 65.6% of older patients (p < 0.0001). In terms of hormone therapy, the proportion of tamoxifen treated patients was significantly lower in young age group (p < 0.0001). No significant difference in radiation therapy between the two groups.
Young age (≤ 40) is an independent risk factor for relapse in operable Saudi breast cancer patients. The fundamental biology of young age breast cancer patients needs to be elucidated.
PMCID: PMC2222639  PMID: 18053234
10.  Adjuvant Chemotherapy and Survival of Elderly Korean Patients with Breast Carcinoma 
Journal of Breast Cancer  2012;15(3):296-305.
The available research work on types of treatment and the efficacy of adjuvant chemotherapy in older Korean patients is insufficient. Henceforth, this report assessed treatment patterns and the relationship between chemotherapy and survival in elderly Korean breast cancer patients.
We identified women over 55 years of age diagnosed with breast cancer from the period 1995 to 2006. Clinicopathologic features and treatment methods were compared for three groups divided on the basis of age: 55 to 59 years, 60 to 69 years, and over 70 years old. The effects of chemotherapy on survival were compared overall and individually for each group.
A total of 832 patients over 55 years of age were included in the present investigation. No statistical differences were observed between the three age groups in clinicopathologic features including tumor size, grade, and stage. However, patients in the elderly group received mastectomy more often when compared to the younger groups (p<0.001). In contrast, there was a decline in radiation treatment and chemotherapy with older age (p<0.001). Overall, patients who received chemotherapy had a significantly increased breast cancer specific survival and overall survival rate when compared to the non-chemotherapy groups (p=0.022). Among the estrogen receptor positive group, no statistical significance was achieved in the survival benefit of chemotherapy. However, in estrogen receptor-negative patients, overall, the chemotherapy groups showed a better survival rate than the non-chemotherapy patients and a similar trend was observed in each age group except in the group comprising of 70 years old patients.
This study describes the survival benefit of adjuvant chemotherapy in Korean patients over 55 years of age, especially in hormone receptor-negative patients. Hence, based on the results of the present report and considering the similarity of clinicopathologic features between age groups, it is proposed that age alone should not be a determinant factor of treatment methods.
PMCID: PMC3468783  PMID: 23091542
Aged; Breast; Carcinoma; Chemotherapy; Survival
11.  Clinicopathologic Characteristics and Prognosis of Gastric Cancer in Young Patients 
Yonago Acta Medica  2012;55(3):57-61.
To determine the clinicopathologic characteristics and prognosis of gastric cancer in young patients, a total of 1985 gastric cancer patients who had undergone gastrectomy at our hospital were reviewed. The male-to-female ratio was significantly lower in the young patients than in either the middle-aged (P < 0.0001) or elderly patients (P < 0.0001). Undifferentiated carcinoma was observed more frequently in the young patients compared with either the middle-aged (P < 0.0001) or elderly patients (P < 0.0001). Furthermore, peritoneal metastasis was observed more frequently in the young patients than in either the middle-aged (P < 0.005) or elderly patients (P < 0.005). Five-year survival rates were 61.0, 73.6 and 68.1% in the young, middle-aged and elderly patients, respectively. The prognosis of the middle-aged patients was significantly better than that of either the young or the elderly patients (P < 0.05). Multivariate analysis indicated that age was an independent prognostic factor. Peritoneal recurrence was more frequently observed in the young patients than either the middle-aged or the elderly patients (P < 0.05). Gastric cancer in young patients has unique characteristics, namely, a predominance of female patients and a high frequency of undifferentiated cancer and peritoneal metastasis and recurrence.
PMCID: PMC3727677  PMID: 24031140
age; gastric cancer; prognosis
12.  Molecular Characteristics and Metastasis Predictor Genes of Triple-Negative Breast Cancer: A Clinical Study of Triple-Negative Breast Carcinomas 
PLoS ONE  2012;7(9):e45831.
Triple-negative breast cancer is a subtype of breast cancer with aggressive tumor behavior and distinct disease etiology. Due to the lack of an effective targeted medicine, treatment options for triple-negative breast cancer are few and recurrence rates are high. Although various multi-gene prognostic markers have been proposed for the prediction of breast cancer outcome, most of them were proven clinically useful only for estrogen receptor-positive breast cancers. Reliable identification of triple-negative patients with a favorable prognosis is not yet possible.
Methodology/Principal Findings
Clinicopathological information and microarray data from 157 invasive breast carcinomas were collected at National Taiwan University Hospital from 1995 to 2008. Gene expression data of 51 triple-negative and 106 luminal breast cancers were generated by oligonucleotide microarrays. Hierarchical clustering analysis revealed that the majority (94%) of triple-negative breast cancers were tightly clustered together carrying strong basal-like characteristics. A 45-gene prognostic signature giving 98% predictive accuracy in distant recurrence of our triple-negative patients was determined using the receiver operating characteristic analysis and leave-one-out cross validation. External validation of the prognostic signature in an independent microarray dataset of 59 early-stage triple-negative patients also obtained statistical significance (hazard ratio 2.29, 95% confidence interval (CI) 1.04–5.06, Cox P = 0.04), outperforming five other published breast cancer prognostic signatures. The 45-gene signature identified in this study revealed that TGF-β signaling of immune/inflammatory regulation may play an important role in distant metastatic invasion of triple-negative breast cancer.
Gene expression data and recurrence information of triple-negative breast cancer were collected and analyzed in this study. A novel set of 45-gene signature was found to be statistically predictive in disease recurrence of triple-negative breast cancer. The 45-gene signature, if further validated, may be a clinically useful tool in risk assessment of distant recurrence for early-stage triple-negative patients.
PMCID: PMC3458056  PMID: 23049873
13.  Clinical Implications of Micrometastasis Detection in Internal Mammary Nodes of Breast Cancer Patients 
Breast Care  2012;7(3):216-219.
The aim of this study was to assess the efficiency of step-serial sectioning (SSS) combined with hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining in detecting micrometastasis of internal mammary lymph nodes (IMLNs).
Patients and Methods
135 IMLNs from 88 breast cancer patients were re-examined by SSS, combined with either H&E or IHC staining of the biomarkers cytokeratin-19 and epithelial membrane antigen.
Of the 135 IMLNs, 6 nodes from 5 cases displayed 1 or more micrometastases. Histological grade and lymphovascular invasion status were significantly correlated with micrometastasis in the IMLNs (p = 0.018 and 0.001, respectively). Of the 6 nodes positive for micrometastasis, 1 node was detected by both H&E and IHC staining. The remaining 5 nodes from 4 cases showed evident tumor cells only by IHC staining. Finally 8 of the 83 patients (9.64%) without IMLN metastasis showed distant metastasis, while 2 of the 5 patients (40%) with IMLN metastasis showed distant metastasis within 28 months of operation.
SSS combined with H&E and IHC staining is more efficient in detecting micrometastasis than classic routine single-slice H&E only.
PMCID: PMC3409387  PMID: 22872795
Breast cancer; Internal mammary nodes; Micrometastasis; Step-serial sectioning
14.  Clinicopathological significance of PTPN12 expression in human breast cancer 
Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is a recently identified tumor suppressor gene (TSG) that is frequently compromised in human triple-negative breast cancer. In the present study, we investigated the expression of PTPN12 protein by patients with breast cancer in a Chinese population and the relationship between PTPN12 expression levels and patient clinicopathological features and prognosis. Additionally, we explored the underlying down-regulation mechanism from the perspective of an epigenetic alteration. We examined PTPN12 mRNA expression in five breast cancer cell lines using semi-quantitative reverse-transcription PCR, and detected PTPN12 protein expression using immunohistochemistry in 150 primary invasive breast cancer cases and paired adjacent non-tumor tissues. Methylation-specific PCR was performed to analyze the promoter CpG island methylation status of PTPN12. PTPN12 was significantly down-regulated in breast cancer cases (48/150) compared to adjacent noncancerous tissues (17/150; P < 0.05). Furthermore, low expression of PTPN12 showed a significant positive correlation with tumor size (P = 0.047), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), histological grade (P = 0.012), and survival time (P = 0.019). Additionally, promoter CpG island hypermethylation occurs more frequently in breast cancer cases and breast cancer cell lines with low PTPN12 expression. Our findings suggest that PTPN12 is potentially a methylation-silenced TSG for breast cancer that may play an important role in breast carcinogenesis and could potentially serve as an independent prognostic factor for invasive breast cancer patients.
PMCID: PMC3854213  PMID: 23044628
Breast cancer; Tumor suppressor gene; PTPN12; Prognosis; Methylation
15.  Ultrasound and Clinicopathological Characteristics of Triple Receptor-Negative Breast Cancers 
Journal of Breast Cancer  2011;14(2):119-123.
Triple receptor-negative (TRN) breast cancer is associated with high risk of recurrence and poor prognosis. The present study assessed the clinicopathologic characteristics and ultrasound (US) features of TRN breast cancers.
Pathological and biological data were reviewed for 558 breast cancer patients treated at Kangbuk Samsung Hospital, between January 2003 and December 2009. The patients were separated into TRN breast cancer and non-TRN breast cancer groups, based on the results of immunohistochemical prognostic panels. Clinical and pathologic features were compared for the two groups. US features, including shape, orientation, margins, boundaries, echo patterns, posterior acoustic features, surrounding tissues, and microcalcifications, were determined for 41 TRN patients and 189 non-TRN controls (ER+/PR+/HER2-).
Of 558 cases, 58 (10.4%) had the TRN phenotype. Four hundred and thirty-four cases (77.8%) were invasive ductal carcinomas. TRN cancer was significantly associated with specific characteristics of tumor size, nuclear grade, histologic grade, venous invasion, and lymphatic invasion. With respect to US features, TRN cancers were more likely to have an oval shape, a circumscribed margin, and marked hypoechogenicity.
Tumor characteristics were different between TRN and non-TRN breast cancers, although US cannot differentiate the subtype of breast cancers TRN cancer tend to show somewhat different US morphology.
PMCID: PMC3148546  PMID: 21847406
Breast neoplasms; Hormone receptor; Pathology; Ultrasouography
16.  Analysis of RhoC expression and lymphovascular emboli in inflammatory vs non-inflammatory breast cancers in Egyptian patients 
Understanding the molecular factors that distinguish inflammatory breast cancer (IBC) from non-IBC is important for IBC diagnosis. We reviewed the records of 48 IBC patients and 64 non-IBC patients from Egypt. We determined RhoC expression and tumor emboli and their relationship to demographic and reproductive characteristics. Compared with non-IBC patients, IBC patients had significantly lower parity (P = 0.018) and fewer palpable tumors (P < 0.0001). IBC tumors showed RhoC overexpression more frequently than non-IBC tumors (87% vs. 17%, respectively) (P < 0.0001). Tumor emboli were significantly more frequent in IBC tumors than non-IBC tumors (Mean ± SD: 14.1 ± 14.0 vs. 7.0 ± 12.9, respectively) (P < 0.0001). This study illustrates that RhoC overexpression and tumor emboli are more frequent in tumors of IBC relative to non-IBC from Egypt. Future studies should focus on relating epidemiologic factors to molecular features of IBC in this population.
PMCID: PMC2818070  PMID: 19157876
Inflammatory breast cancer; Tumor emboli; RhoC; Egypt; Developing countries
17.  Analysis of the Potent Prognostic Factors in Luminal-Type Breast Cancer 
Journal of Breast Cancer  2012;15(4):401-406.
Luminal-type breast cancer has a good prognosis compared to other types, such as human epidermal growth factor receptor 2 and triple negative types. Luminal-type breast cancer is classified into luminal A and B, according to the proliferation index. We investigated the clinicopathological factors that affect the prognosis of the luminal-type subgroups.
We reviewed the medical records and the pathologic reports of 159 luminal-type breast cancer patients who were treated between February 2005 and November 2007. We divided luminal-type breast cancer into luminal A and B, according to Ki-67 (cutoff value, 14%) and analyzed the clinicopathologic factors, such as age at diagnosis, intensity score of estrogen receptor and progesterone receptor, histologic grade, and Bcl-2. Moreover, we compared the disease-free survival (DFS) of each group.
In the univariate analysis, age (p=0.004), tumor size (p=0.010), lymph node metastasis (p=0.001), and Bcl-2 (p=0.002) were statistically significant factors in luminal-type breast cancer. In the multivariate analysis, lymph node (p=0.049) and Bcl-2 (p=0.034) were significant relevant factors in luminal-type breast cancer. In the subgroup analysis, the increased Bcl-2 (cutoff value, 33%) was related with a longer DFS in the luminal B group (p=0.004).
In our study, luminal A breast cancer showed a longer DFS than luminal B breast cancer, further, Bcl-2 may be a potent prognostic factor in luminal-type breast cancer.
PMCID: PMC3542847  PMID: 23346168
Bcl-2; Breast neoplasms; Prognosis
18.  Clinicopathologic Features and Outcomes of Metaplastic Breast Carcinoma: Comparison with Invasive Ductal Carcinoma of the Breast 
Yonsei Medical Journal  2010;51(6):864-869.
Metaplastic breast carcinoma (MBC) is rare. Its clinicopathologic features and prognosis are uncertain. The aim of this study was to evaluate the clinicopathologic characteristics and outcomes in comparison with invasive ductal carcinoma (IDC).
Materials and Methods
We reviewed the data of 29 patients with MBC and 4,851 patients with IDC, who received surgery at Yonsei University Severance Hospital between 1980 and 2008. Various clinicopathologic features, recurrence free, and overall survival were investigated and compared to each other.
Stage IV cases at diagnosis were more common in MBC (10.3%) than in IDC (0.9%). The incidence rates of triple negative breast cancer (TNBC) were significantly higher in MBC (84.0%) than in IDC (20.1%). Larger tumors (>2 cm) and lower tendency of axillary metastasis were frequently observed in MBC. Only one of 24 preoperative core needle biopsies (CNB) correctly diagnosed MBC. There was no significant difference in survival between the two groups.
MBC was characterized by a higher incidence of TNBC, larger tumor size, and lower tendency of axillary metastasis, and was difficult to diagnose with CNB. Although the incidence of stage IV disease at diagnosis was higher in MBC, the survival rates of stage I-III were comparable to those of IDC.
PMCID: PMC2995974  PMID: 20879052
Breast neoplasms; metaplasia; survival; triple negative breast cancer
19.  Efficacy of adjuvant chemotherapy according to hormone receptor status in young patients with breast cancer: a pooled analysis 
Breast cancer at a young age is associated with an unfavorable prognosis. Very young patients with breast cancer therefore are advised to undergo adjuvant chemotherapy irrespective of tumor stage or grade. However, chemotherapy alone may not be adequate in young patients with hormone receptor-positive breast cancer. Therefore, we studied the effect of adjuvant chemotherapy in young patients with breast cancer in relation to hormone receptor status.
Paraffin-embedded tumor material was collected from 480 early-stage breast cancer patients younger than 41 years who participated in one of four European Organization for Research and Treatment of Cancer trials. Using immunohistochemistry on the whole series of tumors, we assessed estrogen receptor (ER) status and progesterone receptor (PgR) status in a standardized way. Endpoints in this study were overall survival (OS) and distant metastasis-free survival (DMFS). The median follow-up period was 7.3 years.
Overall, patients with ER-positive tumors had better OS rates (hazard ratio [HR] 0.63; P = 0.02) compared with those with ER-negative tumors. However, in the subgroup of patients who received chemotherapy, no significant difference in OS (HR 0.87; P = 0.63) and DMFS (HR 1.36; P = 0.23) was found between patients with ER-positive tumors or those with ER-negative tumors. These differences were similar for PgR status.
Young patients with hormone receptor-positive tumors benefit less from adjuvant systemic chemotherapy than patients with hormone receptor-negative tumors. These results confirm that chemotherapy alone cannot be considered optimal adjuvant systemic treatment in breast cancer patients 40 years old or younger with hormone receptor-positive tumors.
PMCID: PMC2242667  PMID: 17931406
20.  Evaluation of prognostic factors in stage IIA breast tumors and their correlation with mortality risk 
Clinics  2011;66(4):607-612.
Breast tumors exhibit extensive molecular and clinical heterogeneity. One of the most utilized breast carcinoma classifications is based on its molecular aspects and subdivides breast cancer into five major groups based on the expression of certain genes. In this study, we evaluated which factors are important in determining a prognosis after 5 years of follow-up for patients with clinical stage IIA breast tumors. We took into consideration the different phenotypes (luminal A luminal B HER-2 overexpression, basal and triple-negative), various epithelial-mesenchymal (EMT) molecular markers and adhesion molecules (E-cadherin, P-cadherin, N-cadherin, vimentin, twist snail and slug) and NOS-2, in addition to clinical and demographic data, tumor characteristics and treatment types.
The study population consisted of 82 patients with breast cancer. We analyzed eight molecular markers by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with ten years of follow-up, and we classified each tumor according to its estrogen receptor, progesterone receptor and HER-2 expression. We then placed the tumor into one of the above categories.
The presence of several clinical and demographic factors, various histopathologies, treatment forms and several immunohistochemical markers were not associated with a worse prognosis for group IIA patients. The factors that were associated with a mortality risk were the triple-negative (odds ratio (OR) = 11.8, 95% confident interval (CI) = 2.0-70.3, P = 0.007) and basal (OR = 18.4, 95% CI = 1.8-184.7, P = 0.013) phenotypic patterns.
The EMT markers and NOS-2 were not mortality risk factors. Basal and triple-negative phenotypic patterns were related to a higher mortality risk in patients with stage IIA tumors.
PMCID: PMC3093790  PMID: 21655754
Breast cancer; molecular markers; staging; tissue microarray; immunohistochemistry
21.  Significance of preoperative C-reactive protein as a parameter in patients with small cell carcinoma of the esophagus 
OncoTargets and therapy  2013;6:1147-1151.
C-reactive protein (CRP) is inversely related to prognosis in many cancers, however, no studies regarding the predictive value of CRP in small cell carcinoma of the esophagus (SCCE) are available. The aim of this study was to determine the prognostic value of preoperative CRP in patients with SCCE.
From January 2001 to December 2010, a retrospective analysis of 43 consecutive patients with SCCE was conducted. Univariate and multivariate analyses were performed to evaluate the prognostic parameters.
In our study, elevated CRP levels (>10 mg/L) were found in 16 patients (37.2%). CRP levels were significantly higher in patients with deeply invasive tumors (P = 0.018) and those associated with nodal metastasis (P = 0.018). Patients with CRP ≤10 mg/L had a significantly better overall survival than patients with CRP >10 mg/L (25.9% vs 6.3%, P = 0.004). Multivariate analyses showed that CRP was a significant predictor for overall survival. CRP >10 mg/L had a hazard ratio of 2.756 (95% confidence interval: 1.115–6.813, P = 0.028) for overall survival.
Preoperative CRP is an independent predictive factor for long-term survival in patients with SCCE.
PMCID: PMC3758215  PMID: 24009425
C-reactive protein; esophageal cancer; small cell carcinoma; survival
22.  Impact of established prognostic factors and molecular subtype in very young breast cancer patients: pooled analysis of four EORTC randomized controlled trials 
Young age at the time of diagnosis of breast cancer is an independent factor of poor prognosis. In many treatment guidelines, the recommendation is to treat young patients with adjuvant chemotherapy regardless of tumor characteristics. However, limited data on prognostic factors are available for young breast cancer patients. The purpose of this study was to determine the prognostic value of established clinical and pathological prognostic factors in young breast cancer patients.
Data from four European Organisation for Research and Treatment of Cancer (EORTC) clinical trials were pooled, resulting in a dataset consisting of 9,938 early breast cancer patients with a median follow-up of 11 years. For 549 patients aged less than 40 years at the time of diagnosis, including 341 node negative patients who did not receive chemotherapy, paraffin tumor blocks were processed for immunohistochemistry using a tissue microarray. Cox proportional hazard analysis was applied to assess the association of clinical and pathological factors with overall and distant metastasis free survival.
For young patients, tumor size (P = 0.01), nodal status (P = 0.006) and molecular subtype (P = 0.02) were independent prognostic factors for overall survival. In the node negative subgroup, only molecular subtype was a prognostic factor for overall survival (P = 0.02). Young node negative patients bearing luminal A tumors had an overall survival rate of 94% at 10 years' follow-up compared to 72% for patients with basal-type tumors.
Molecular subtype is a strong independent prognostic factor in breast cancer patients younger than 40 years of age. These data support the use of established prognostic factors as a diagnostic tool to assess disease outcome and to plan systemic treatment strategies in young breast cancer patients.
PMCID: PMC3218957  PMID: 21699739
23.  Comparative Study of Complete and Partial Omentectomy in Radical Subtotal Gastrectomy for Early Gastric Cancer 
Yonsei Medical Journal  2011;52(6):961-966.
Curative surgery for patients with advanced or even early gastric cancer can be defined as resection of the stomach and dissection of the first and second level lymph nodes, including the greater omentum. The aim of this study was to evaluate the short- and long- term outcomes of partial omentectomy (PO) as compared with complete omentectomy (CO).
Materials and Methods
Seventeen consecutive open distal gastrectomies with POs were initially performed between February and July in 2006. The patients' clinicopathologic data and post-operative outcomes were retrospectively compared with 20 patients who underwent open distal gastrectomies with COs for early gastric cancer in 2005.
The operation time in PO group was significantly shorter than that in CO group (142.4 minutes vs. 165.0 minutes, p=0.018). The serum albumin concentration on the first post-operative day in PO group was significantly higher than CO group (3.8 g/dL vs. 3.5 g/dL, p=0.018). Three postoperative minor complications were successfully managed with conservative treatment. Median follow-up period between PO and CO was 38.1 and 37.7 months. All patients were alive without recurrence until December 30, 2009.
PO during open radical distal gastrectomy can be considered a more useful procedure than CO for treating early gastric cancer. To document the long-term technical and oncologic safety of this procedure, a large-scale prospective randomized trial will be needed.
PMCID: PMC3220242  PMID: 22028160
Partial omentectomy; gastric cancer; post-operative outcome; comparative study
24.  Polymorphisms in XPD and ERCC1 Associated with Colorectal Cancer Outcome 
Using the comprehensive approach to selecting polymorphisms to date, we sought to examine whether recurrence in colorectal cancer was associated with inherited variation in three genes involved in DNA repair and cell proliferation. Three polymorphisms, which are excision repair cross-complementation 1 (ERCC1), xeroderma pigmentosum group D (XPD) and epidermal growth factor receptor (EGFR), were assessed in 257 postoperative stage II/III CRC patients with 5-fluorouracial chemotherapy in Taiwan. In addition, the correlations between genetic polymorphisms and patients’ clinicopathological features were investigated. Genotypes of XPD codon751 A/A and ERCC1 codon118 T/T were associated with regional recurrence in a statistically significant way (p = 0.018). Patients who carried XPD AA and ERCC1 TT genotypes demonstrated a significantly greater regional recurrence risk (OR = 5.625, 95% CI, 1.557–20.32). Inherited variation in XPD and ERCC1 was associated with outcome in patients with colorectal cancer in Taiwan. As the significant association of single-nucleotide polymorphisms has not been studied previously in colorectal cancer, these findings suggest novel sites of variation, in part explaining the range of treatment responses seen in this disease.
PMCID: PMC3588089  PMID: 23429196
genetic polymorphism; XPD; ERCC1; colorectal cancer; regional recurrence
25.  Multiple Margin Positivity of Frozen Section Is an Independent Risk Factor for Local Recurrence in Breast-Conserving Surgery 
Journal of Breast Cancer  2012;15(4):420-426.
Breast-conserving surgery (BCS) with radiotherapy has become a standard treatment for early stage breast cancer, since the installation of NSABP B-06. One of the serious problems in BCS is that of local recurrence. There are many risk factors for local recurrence, such as large tumor size, multiple tumors, axillary lymph node involvement, young age, high nuclear grade, and so on. The aim of this study is to identify patients with a higher risk of local recurrence of breast cancer.
Between January 2002 and December 2006, 447 patients with breast cancer, and who had undergone BCS with immediate breast reconstruction, were enrolled in the study. The follow-up period was 5 years from the time of operation and we analyzed local recurrence, disease-free survival (DFS), and overall survival (OS). The analysis included various clinicopathological factors such as age, chemotherapy, radiotherapy, hormone therapy, pathologic characteristics, and margin status. Statistical analysis was performed with log-rank test and Kaplan-Meier method. The p-value <0.05 was considered statistically significant.
The mean follow-up period was 88 months and local recurrence of breast cancer occurred only in 16 cases (3.6%). The actual 5-year DFS, and OS rates were 90.6% and 93.3%, respectively. For the local recurrence of breast cancer, positive margin status, multiple margin positivity, conversed margin cases, T/N stages showed statistical significance in univariate analysis. However, only multiple margin positivity was identified as an independent risk factor for local recurrence in multivariate analysis.
When the multiple margin positivity is diagnosed on intraoperative frozen biopsy, surgeons should consider a much wider excision of the breast and a more aggressive management.
PMCID: PMC3542850  PMID: 23346171
Breast neoplasms; Local neoplasm recurrence; Segmental mastectomy

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