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1.  ROS1 Expression in Invasive Ductal Carcinoma of the Breast Related to Proliferation Activity 
Yonsei Medical Journal  2013;54(3):650-657.
Purpose
ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression patterns and to verify the association with prognostic factors in invasive ductal carcinoma (IDC) of the breast.
Materials and Methods
Tissue samples from 203 patients were used. Forty-six cases were available for fresh tissue. We performed immunohistochemical staining and real-time polymerase chain reaction (PCR).
Results
ROS1 expression was significantly lower in proportion to higher histologic grade, higher mitotic counts, lower estrogen receptor expression, and a higher Ki-67 proliferation index, although ROS1 expression was not significantly associated with the survival rate. The result of real-time PCR revealed similar trends, however not statistically significant.
Conclusion
Higher ROS1 expression may be associated with favorable prognostic factors of IDC and its expression in IDC is related to the proliferation of tumor cells.
doi:10.3349/ymj.2013.54.3.650
PMCID: PMC3635654  PMID: 23549810
Breast; invasive ductal carcinoma; prognostic factors; proliferation rate; ROS1
2.  Usefulness of Pretreatment Neutrophil to Lymphocyte Ratio in Predicting Disease-Specific Survival in Breast Cancer Patients 
Journal of Breast Cancer  2013;16(1):55-59.
Purpose
The purpose of this study was to investigate the prognostic impact of pretreatment neutrophil to lymphocyte ratio (NLR) on breast cancer in view of disease-specific survival and the intrinsic subtype.
Methods
We retrospectively studied patients diagnosed with primary breast cancer that had completed all phases of primary treatment from 2000 to 2010. The association between pretreatment NLR and disease-specific survival was analyzed.
Results
A total of 442 patients were eligible for analysis. Patients with higher NLR (2.5 ≤NLR) showed significantly lower disease-specific survival rate than those with lower NLR (NLR <2.5). Higher NLR along with negative estrogen receptor status and positive nodal status were independently correlated with poor prognosis, with hazard ratio 4.08 (95% confidence interval [CI], 1.62-10.28), 9.93 (95% CI, 3.51-28.13), and 11.23 (95% CI, 3.34-37.83), respectively. Luminal A subtype was the only intrinsic subtype in which higher NLR patients showed significantly poor prognosis (87.7% vs. 96.7%, p=0.009).
Conclusion
Patients with an elevated pretreatment NLR showed poorer disease-specific survival than patients without elevated NLR, most evident in the luminal A subtype. Further validation and a feasibility study are required before it can be considered for clinical use.
doi:10.4048/jbc.2013.16.1.55
PMCID: PMC3625770  PMID: 23593082
Breast neoplasms; Lymphocytes; Neutrophils
3.  The diagnostic values of preoperative laboratory markers in children with complicated appendicitis 
Purpose
Accurate diagnosis and optimal management of acute appendicitis, despite being the most common surgical emergency encountered in emergency departments, is often delayed in pediatric patients due to nonspecific symptoms and communication barriers, often leading to more complicated cases. The aim of this study is to investigate the diagnostic significance of common laboratory markers.
Methods
A total of 421 patients aged 15 and younger underwent surgical treatment for acute appendicitis. We conducted a retrospective analysis for white blood cell (WBC), C-reactive protein (CRP) and bilirubin. All patients were classified into simple or complicated appendicitis groups based on postoperative histology.
Results
The mean age of the patients in the complicated appendicitis group was younger than that in the simple group (P = 0.005). WBC, CRP and bilirubin levels were significantly higher in the complicated appendicitis group (P < 0.001, <0.001, 0.002). The relative risk for complicated appendicitis was calculated using age, WBC, CRP and bilirubin. Elevated CRP levels were associated with the highest risk for complicated appendicitis (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.38 to 4.65) followed by WBC (HR, 2.42; 95% CI, 1.07 to 5.46) and bilirubin (HR, 2.04; 95% CI, 1.09 to 3.82). The most sensitive markers for diagnosing complicated appendicitis were WBC (95.2%) and CRP (86.3%). Bilirubin levels showed the highest specificity at 74.8%.
Conclusion
The risk of complicated appendicitis was significantly higher in patients younger than 10 years old. Preoperative WBC, CRP and bilirubin have clinical value in diagnosing complicated appendicitis with a HR of 2.0 to 2.5. Our results suggest that the utilization of WBC, CRP, and bilirubin can assist in the diagnosis of complicated appendicitis in pediatric patients, allowing prompt diagnosis and optimal management.
doi:10.4174/jkss.2012.83.4.237
PMCID: PMC3467390  PMID: 23091796
Appendicitis; Child; Leukocytes; C-reactive protein; Bilirubin
4.  HDAC1 Expression in Invasive Ductal Carcinoma of the Breast and Its Value as a Good Prognostic Factor 
Korean Journal of Pathology  2012;46(4):311-317.
Background
Histone deacetylase 1 (HDAC1) is associated with the expression and function of estrogen receptors and the proliferation of tumor cells, and has been considered a very important factor in breast tumor progression and prognosis. Several studies have reported an association between HDAC1 expression and poorer prognosis in cancers including breast cancer, with a few exceptions. However, because of the dearth of studies on HDAC1 expression in breast cancer, its significance for breast cancer prognosis has not been well defined. Therefore, we examined HDAC1 expression in invasive ductal carcinoma (IDC), the most common breast cancer, and investigated its potential prognostic significance.
Methods
We used 203 IDC tissue samples. Immunohistochemical stains for HDAC1 and real-time polymerase chain reaction for HDAC1 mRNA were performed and the results were compared to generally well-established prognostic factors in breast cancer and patient survival rates.
Results
HDAC1 expression was significantly reduced in proportion to higher histologic grade, higher nuclear pleomorphism score, and higher mitotic counts, and with lower estrogen receptor expression. Furthermore, it was significantly associated with the survival rate.
Conclusions
HDAC1 expression is a good prognostic indicator in IDC.
doi:10.4132/KoreanJPathol.2012.46.4.311
PMCID: PMC3479820  PMID: 23110022
Breast; Histone deacetylase1; Carcinoma, ductal, breast; Prognostic factors; Proliferation rate
5.  Expressional Difference of RHEB, HDAC1, and WEE1 Proteins in the Stromal Tumors of the Breast and Their Significance in Tumorigenesis 
Korean Journal of Pathology  2012;46(4):324-330.
Background
Fibroadenoma (FA) and phyllodes tumor (PT) are stromal tumors of breast and are histologically similar. There are no established differences in tumorigenesis and oncogene expression among them. Ras homolog enriched in brain (RHEB) plays an important role in cell growth and cell-cycle control, histone deacetylase 1 (HDAC1) is an important factor in breast tumor progression and prognosis, and WEE1 homolog (WEE1) functions as a tumor suppressor. No studies on the expressional differences of these proteins in FA and PT have been reported to date.
Methods
The expression of these proteins in FA, PT, and normal breast was compared. We used 102 cases of FA and 25 cases of benign PT.
Results
In epithelial cells, the expression of RHEB, HDAC1, and WEE1 was lowest in PT, higher in FA, and most enhanced in normal breast. In addition, the expression of RHEB and HDAC1 was higher in the stromal cells of PT than in FA and normal breast.
Conclusions
Both epithelial and stromal cells of FA and PT express these proteins, which indicates that epithelial cells play an important role in the development of stromal tumors. In addition, the expressional differences of these proteins may be associated with the tumorigenesis of breast stromal tumors.
doi:10.4132/KoreanJPathol.2012.46.4.324
PMCID: PMC3479826  PMID: 23110024
Breast neoplasms; HDAC1 protein; RHEB protein; Stromal cells; WEE1 protein

Results 1-5 (5)