PURPOSE: The purpose of this study was to investigate the prognostic significance of the expression of EGFR and C-erbB-2 gene products by immunohistochemical analysis for curatively resected gastric adenocarcinoma. MATERIALS AND METHODS: Between January 1996 and December 2001, 739 patients with curatively resected gastric cancer patients underwent Immunohistochemical staining for EGFR and C-erbB-2 proteins, and we retro spectively analyzed their correlation with the clinical outcome. RESULTS: The overexpressions of EGFR and C-erbB-2 were 25.4% and 26.2%, respectively. The overexpressions of EGFR was associated with the more poorly differentiated tumor (p=0.000) and with neuronal invasion (p=0.03). Overexpression of C-erbB-2 was associated with less vascular invasion (p=0.001). Tumor depth or node metastasis was not related to the overexpression of EGFR or C-erbB-2. The seven-year overall survival and relapse-free survival rates were 87.2% and 75.8%, respectively. Upon multivariate Cox regression analysis, the tumor stage, tumor size and patient age were important prognostic factors for overall survival, and tumor stage was the important factor for relapse-free survival. Overexpressions of EGFR or c-erbB-2 were not significant prognostic factors. CONCLUSION: Immunohistochemical staining of EGFR and C-erbB-2 gene products were not independent prognostic factors for predicting the overall survival and the relapse-free survival in curatively resected gastric cancer.
Adenocarcinoma ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Neurons ; Prognosis ; Receptor, erbB-2 ; Regression Analysis ; Stomach Neoplasms*

Breast Neoplasms ; chemistry ; genetics ; Chromogenic Compounds ; Female ; Genes, erbB-2 ; Humans ; In Situ Hybridization ; methods ; Receptor, ErbB-2 ; analysis

Breast Neoplasms ; diagnosis ; therapy ; Early Detection of Cancer ; Female ; Humans ; Practice Guidelines as Topic ; Receptor, ErbB-2 ; analysis

Breast Neoplasms ; chemistry ; Female ; Humans ; Practice Guidelines as Topic ; Receptor, ErbB-2 ; analysis ; Time Factors

Fox transcription factors play a critical role in the regulation of a variety of biological processes. While FoxM1 behaves like the oncogenic transcription factor, FoxO3a is known as a tumor suppressor by inhibiting FoxM1. This study aimed to investigate the clinicopathological significance of FoxM1 and FoxO3a expression in breast cancer. Expression of FoxM1 and FoxO3a were analyzed by immunohistochemical staining on tissue microarray sections from 236 breast cancer patients, and correlated with various clinicopathological characteristics. Overexpression of FoxM1 correlated with adverse clinicopathological features, such as larger tumor size, lymph node metastasis, advanced tumor stage, and lymphovascular invasion. The Kaplan-Meier survival curves revealed no prognostic significance of FoxM1 expression. However, in subgroup analyses with patients of estrogen receptor (ER) positive breast cancers, FoxM1 overexpression associated with poor disease free and overall survival. No association was found between FoxO3a and FoxM1 expression. Regarding clinicopathological variables, the only association between histologic grade and FoxO3a was observed. In conclusion, FoxM1 overexpression was significantly associated with aggressive phenotypes and poor prognosis of ER-positive breast cancer. These findings suggest the possible role of FoxM1 as a prognostic biomarker and putative target of anti-cancer therapy.
Breast Neoplasms/chemistry/mortality/*pathology ; Female ; Forkhead Transcription Factors/*analysis ; Humans ; Phenotype ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/*analysis

PURPOSE: Among more than 500 microRNAs, microRNA-21 (miR-21) is known to act as an oncogene. The aim of this study was to investigate the significance of miR-21 expression level in relation with clinicopathological factors and prognosis in breast cancer. METHODS: MicroRNA was extracted from cancer and normal breast tissue of 109 breast cancer patients who underwent surgery from 2002 to 2004 using the Taqman(R) MicroRNA Assay. The correlation between miR-21 expression and clinicopathologic features was analyzed and the significance of miR-21 as a prognostic factor and its relationship with survival was determined. RESULTS: MiR-21 expression was higher in cancer tissues than in normal tissues (p<0.0001). High miR-21 expression was associated with mastectomy, larger tumor size, higher stage, higher grade, estrogen receptor (ER) negative, human epidermal growth factor receptor 2 (HER2) positive, HER2 positive breast cancer subtype, high Ki-67 expression, and death. On multivariate analysis, prognostic factors for overall survival were ER and miR-21. High miR-21 expression was significantly related to lower overall survival (p=0.031). CONCLUSION: This study supports the role of miR-21 as an oncogene and a biomarker for breast cancer with its high expression in cancer tissues and its relationship with other prognostic factors and survival.
Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Estrogens ; Humans ; Mastectomy ; MicroRNAs ; Multivariate Analysis ; Oncogenes ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2

BACKGROUNDThe aim of this study was to investigate DNA content and expression of c-erbB-2, PS2, and prostate-specific antigen (PSA) proteins in breast carcinomas with neuroendocrine (NE) cell differentiation.

METHODSChromogranin, c-erbB-2, PS2, and PSA in 131 samples of breast cancer were detected immunohistochemically. Classic Feulgen staining image analysis techniques were used to quantify DNA content in 81 of the breast cancer samples.

RESULTSThe c-erbB-2 positive rate in breast carcinoma samples containing neuroendocrine cells was 37.5% and the rate of high expression of c-erbB-2 (++ or +++) was 33.3%, both significantly lower than that in breast carcinomas without neuroendocrine cells (62.6% and 68.7%, respectively, P < 0.05). The rates of positive PS2 and PSA expression in breast carcinoma samples containing neuroendocrine cells were 72.2% and 55.0%, respectively, both significantly higher than that in breast carcinoma samples without neuroendocrine cells (45.0% and 16.4%, respectively, P < 0.05). In NE(+) samples, the integral optical density, DNA index, DNA stemline peak, > 5 c aneuploidy cells, and rate of aneuploidy among cells were all lower than that in NE(-) breast carcinomas (P < 0.01). In NE(+) grade I or II breast carcinomas, these indices were also all lower than that in the NE(-) breast carcinoma samples (P < 0.01).

CONCLUSIONBreast carcinomas with neuroendocrine differentiation have a lower rate of malignancy. Neuroendocrine differentiation could serve as a prognostic marker in clinical practice.

Breast Neoplasms ; chemistry ; pathology ; Cell Differentiation ; DNA ; analysis ; Female ; Humans ; Membrane Proteins ; analysis ; Neurosecretory Systems ; cytology ; Presenilin-2 ; Prostate-Specific Antigen ; analysis ; Receptor, ErbB-2 ; analysis

PURPOSE: A clinical trial that evaluated the efficacy of Herceptin(R) (anti-erbB2 antibody) as a first-line therapy for metastatic breast cancer was presented. It was demonstrated that 38% of the metastatic breast cancer patients benefited clinically from the Herceptin therapy. Recently, a trial of systemic chemotherapy was recommended as a first-line treatment for the patient with metastatic breast cancer refractory to Herceptin therapy. Therefore, it is necessary to evaluate c-erbB-2 protein expression in breast cancer prior to Herceptin treatment and the significance of c-erbB-2 protein as a prognostic predictor. METHODS: To evaluate c-erbB-2 protein as a prognostic predictor, we analyzed the expression of c-erbB-2 protein by the immunohistochemical method in comparison with other factors such as age, tumor size, stage, histologic grade, LN status, hormonal receptor status and DNA ploidy. Then we performed survival analysis. A total of 266 patients who underwent mastectomy between May 1998 and April 2000 were evaluated and statistical significance was determined by x2 test. RESULTS: In 146 of the 266 patients (54.9%) c-erbB-2 was positive in the tumor, and negative in the remaining 120. The overexpression of c-erbB-2 was positively correlated with tumor size and progesterone receptor positivity. The c-erbB-2 expression showed an association with a low recurrence-free survival probability in univariate analysis (P=0.0159). However, in multivariate analysis, c-erbB-2 expression was not an independent prognostic factor. CONCLUSION: The c-erbB-2 protein expression appears to have prognostic significance in breast cancer but long-term follow-up studies are necessary for confirmation.
Breast Neoplasms* ; Breast* ; DNA ; Drug Therapy ; Follow-Up Studies ; Humans ; Mastectomy ; Multivariate Analysis ; Ploidies ; Receptor, erbB-2* ; Receptors, Progesterone ; Trastuzumab

OBJECTIVETo evaluate the application of the immunohistochemistry (IHC) and the fluorescence in situ hybridization (FISH) in detecting the amplification and the expression of HER-2 gene in the breast cancer patients.

METHODSSixty-six cases of paraffin-embeded breast cancer samples with overexpression, low or no expression of HER-2 gene as detected by IHC were analyzed for HER-2 gene amplification using FISH.

RESULTSAmong the 42 samples with HER-2 gene overexpression (3+/2+) detected by IHC, 31 showed positive HER-2 gene amplification and 11 showed negative HER-2 gene amplification in FISH. In the 24 samples with low or no HER-2 gene expression (1+/-) detected by IHC, no HER-2 gene amplification was detected by FISH. The results of the two testing methods showed a good consistency with the kappa coefficient of 0.672 (P<0.001). We also found that the 17 chromosome polysomy in 42% of the samples and the incidence of 17 polysomy was significantly higher in the HER-2 gene overexpression (3+/2+) group than in low or no HER-2 gene expression (1+/-) group (chi(2)=4.688, P=0.03).

CONCLUSIONIHC can be used as a screening method for detecting HER-2 gene amplification, and FISH should be performed in cases of HER-2 gene overexpression (3+/2+) as detected by IHC.

Breast Neoplasms ; genetics ; metabolism ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Receptor, ErbB-2 ; analysis ; genetics

Breast Neoplasms ; chemistry ; Female ; Humans ; Immunohistochemistry ; methods ; standards ; In Situ Hybridization, Fluorescence ; methods ; standards ; Receptor, ErbB-2 ; analysis ; Stomach Neoplasms ; chemistry