Association between epidermal growth factor receptor gene copy number and ERCC1, BRCA1 protein expression in Chinese patients with non-small cell lung cancer.

Mutation in epidermal growth factor receptor (EGFR) gene may predict response to chemotherapy in non-small cell lung cancer (NSCLC). However, the correlation between EGFR gene copy status and protein levels of drug-resistant genes, such as excision repair cross-complementing 1 (ERCC1) and breast cancer 1 (BRCA1), remains unclear. We retrospectively analyzed formalin-fixed, paraffin-embedded tumor tissues from 109 Chinese patients with NSCLC. EGFR gene copy number was evaluated by fluorescence in situ hybridization (FISH), and protein levels of platinum-resistance-associated genes, including ERCC1 and BRCA1, were determined by immunohistochemical staining. High EGFR gene copy (EGFR FISH-positive) was found in 21.1% of the patients (amplification in 7.3% and high polysomy in 13.8%, respectively). Immunohistochemical analysis revealed that ERCC1 protein expression was not associated with clinicopathological factors, whereas a significantly higher BRCA1 positive rate was found in poorly differentiated tumors (P=0.02). Further association studies demonstrated that EGFR gene copy number status was not correlated with protein levels of ERCC1 or BRCA1; however, expression of ERCC1 was significantly associated with that of BRCA1 in this set of Chinese patients with NSCLC (P<0.001, r=0.484). Our study demonstrated that EGFR gene copy number status was not correlated with ERCC1 or BRCA1 protein expression, but ERCC1 protein levels were significantly correlated to BRCA1 protein expression levels in tumor tissues from Chinese patients with NSCLC.

High expression levels of class III ß-tubulin in resected non-small cell lung cancer patients are predictive of improved patient survival after vinorelbine-based adjuvant chemotherapy.

The aim of the present study was to determine the frequency and predictive value of the expression of tumor microtubule components in patients with resected non-small cell lung cancer (R-NSCLC) subsequently treated with vinorelbine-based adjuvant chemotherapy. The expression of the microtubule components was evaluated in 85 R-NSCLC tumor samples using immunohistochemistry. All patients received vinorelbine-based chemotherapy. The predictive value of microtubule protein expression for disease-free survival (DFS) and overall survival (OS) was assessed. The expression of the microtubule components was not associated with any baseline clinicopathological factors in the R-NSCLC patients. High tumor expression levels of class III ß-tubulin were correlated with an improved DFS (P=0.033) and a trend towards a longer OS (P=0.226). Class II and IV ß-tubulins were not correlated with patient outcome. Multivariate analysis of factors, including gender, age, histology, stage and class II, III and IV ß-tubulin expression demonstrated that high levels of class III ß-tubulin expression were correlated independently with DFS (P= 0.031). These findings suggest that high class III ß-tubulin expression levels in resected tumors are predictive of improved DFS in R-NSCLC patients receiving vinorelbine-based chemotherapy.

[EGFR gene copy number, ERCC1 and BRCA1 protein expression and their relationship in non-small cell lung cancer].

OBJECTIVE: To evaluate the expression of epidermal growth factor receptor (EGFR) gene copy number and the expression of ERCC1 and BRCA1 proteins in patients with non-small-cell lung cancer (NSCLC) and the correlation between them. METHODS: The status of EGFR gene copy number was determined by in situ hybridization (FISH), and the expression of ERCC1 and BRCC1 proteins was examined by immunohistochemistry (IHC). The relationship of EGFR gene copy number with the expression of ERCC1 and BRCA1 and the clinical pathologic features were analyzed. RESULTS: FISH-positive EGFR expression was identified in 40 of 166 samples (24.1%). More FISH-positive EGFR in the female than male patients (31.9% vs. 18.6%, P = 0.048), and non-smoker than smoker (32.8% vs. 16.7%, P = 0.045). FISH-positive EGFR was not associated with age, pathological type, clinical stage and metestasis status (P > 0.05). The expression of ERCC1 protein was identified in 60 of 132 samples (45.5%). The expression of ERCC1 protein varied significantly in tumors of different pathological types (P = 0.046), but not associated with age, gender, clinical stage, metestatic status and smoking status (P > 0.05). The expression of BRCA1 protein was identified in 46 of 131 samples (35.1%). The expression of BRCA1 was not associated with age gender, pathological type, clinical stage, metestatic ststus and smoking status (P > 0.05). There was a moderate correlation between the expressions of ERCC1 and BRCA1 (r = 0.449, P < 0.001), but EGFR gene copy number was not correlated with the expression of ERCC1 or BRCA1 protein. CONCLUSIONS: FISH-positive EGFR expression is associated with gender and smoking status, but not correlated with the expression of ERCC1 and BRCA1 proteins. There is a moderate correlation between the expressions of ERCC1 and BRCA1.

The expression and clinical significance of CLIC1 and HSP27 in lung adenocarcinoma.

The purpose of this research was to study the roles of chloride intracellular channel protein 1 (CLIC1) and heat shock protein 27 (HSP27) in the clinical pathology of lung adenocarcinoma and to explore whether the expression of CLIC1 and HSP27 can be used as independent factors for the prediction of recurrence and prognosis after radical resection of lung adenocarcinoma. One hundred and three paraffin sections of lung adenocarcinoma tissues were collected, and the expression of CLIC1 and HSP27 was detected in these tumors using immunohistochemistry. The correlation of the expression of these two proteins with clinicopathological parameters and prognosis was statistically analyzed. In the 103 samples, the expression of HSP27 and CLIC1 was strongly positive in 61 (59.2%) and 49 cases (47.6%), respectively. Statistical analysis showed that the expression level of HSP27 did not significantly correlate with the patient's age, sex, degree of tumor differentiation, T staging of tumors, and TNM staging of tumors (p > 0.05), whereas the expression of CLIC1 did significantly correlate with T staging of tumors (p = 0.029). Univariate analysis indicated that the patient's ECOG score, T staging, N staging, TNM staging, and CLIC1 expression correlated with prognosis (p = 0.031, 0.001, 0.011, 0.013, and <0.001, respectively). Multivariate statistical analysis showed that age, T staging, and CLIC1 expression were independent associated factors for predicting the 5-year survival rate of patients (p = 0.026, 0.004, and <0.001, respectively). Age, T staging, and CLIC1 expression significantly correlated with the overall survival of post-operative lung adenocarcinoma patients. CLIC1 may be closely associated with the occurrence and development of lung adenocarcinoma and may be used as an effective marker for predicting the prognosis of this disease.

Prognostic impact of MMP-2 and MMP-9 expression in pathologic stage IA non-small cell lung cancer.

BACKGROUND: The purpose of the present study was to assess the value of matrix metalloproteinase (MMP)-2 and MMP-9 expression and other potential prognostic factors in predicting the clinical outcome of patients after definitive surgery for pathologic stage IA non-small cell lung cancer (NSCLC). METHODS: One hundred and forty-six consecutive and non-selected patients who underwent definitive surgery for stage IA NSCLC were included in this study. Formalin-fixed paraffin-embedded specimens were stained for MMP-2 and MMP-9, which were statistically evaluated for their prognostic value and other clinicopathological parameters. RESULTS: Of the 146 patients studied, 102 (69.9%) cases were classified as having high expression for MMP-2. A total of 89 carcinomas (61.0%) had high expression for MMP-9. MMP-9 expression correlated with Eastern Cooperative Oncology Group (ECOG) performance status, pT stage, and differentiation (P = 0.005, <0.001, and <0.001, respectively). Vessel invasion, pT stage, and MMP-9 expression maintained their independent prognostic influence on overall survival (P = 0.037, <0.001, and <0.001, respectively). CONCLUSIONS: From results of our relatively large database, MMP-9 may be considered as a viable biomarker that can be used in conjunction with other prognostic factors such as vessel invasion and pT stage to predict the prognosis of patients with completely resected pathologic stage IA NSCLC.

Heat shock protein-60 expression was significantly correlated with the prognosis of lung adenocarcinoma.

BACKGROUND: The purpose of this study was to investigate the role of heat shock protein 60 (HSP60) in the clinical pathology of lung adenocarcinoma, and to explore whether the expression of HSP60 can act as an independent predictor for tumor relapse and prognosis after radical resection of lung adenocarcinoma. METHODS: Paraffin sections of lung adenocarcinoma tumor tissues were collected from 103 patients. Using immunohistochemistry, the expression levels of HSP60 in lung adenocarcinoma were detected. The correlations between HSP60 expression and clinicopathological parameters as well as prognosis were statistically analyzed. RESULTS: Of the 103 specimens, 70 cases (68.0%) showed a strongly positive expression of HSP60, five cases (4.8%) showed a negative expression, and 28 cases (27.2%) showed a weakly positive expression. The level of HSP60 expression was significantly correlated with TNM stage of the tumor (P = 0.015), and Eastern Cooperative Oncology Group (ECOG) performance status (P = 0.027). Multivariate statistical analysis showed that patient age, pathological T stage, N stage, and HSP60 expression were independent prognostic influence on disease-free survival (P = 0.008, 0.011, 0.010, and <0.001, respectively). CONCLUSIONS: HSP60 may be a good biomarker to be applied in clinic to predict the prognosis of patients with lung adenocarcinoma.

Prognostic impact of nm23-H1 and PCNA expression in pathologic stage I non-small cell lung cancer.

INTRODUCTION: The purpose of this study was to evaluate the value of nm23-H1 and proliferating cell nuclear antigen (PCNA) expression as well as other confirmed prognostic factors in predicting the clinical outcome after definitive surgery of pathologic stage I non-small cell lung cancer (NSCLC). METHODS: Four hundred fifty-two consecutive and non-selected patients who underwent definitive surgery for stage I NSCLC were included in this study. Formalin-fixed paraffin-embedded specimens were stained for nm23-H1 and PCNA, the correlation between the staining and its clinicopathological parameters, and its prognostic power were analyzed statistically. RESULTS: Of the 452 patients studied, 320 cases (70.8%) were high expression for nm23-H1. A total of 182 carcinomas (40.3%) were PCNA high expression tumors. PCNA expression correlated with serum CEA level (P < 0.001), and differentiation (P < 0.001). In univariate analysis by log-rank test, serum CEA level, pT stage, differentiation, nm23-H1 expression, and PCNA expression were significant prognostic factors (P = 0.037, 0.021, <0.001, 0.042, and 0.014, respectively). In multivariate analysis, pT stage and nm23-H1 expression maintained its independent prognostic influence on overall survival (P = 0.041 and 0.003, respectively). CONCLUSIONS: nm23-H1 may be a good biomarker to be applied in clinic to predict the prognosis of patients with completely resected pathologic stage I NSCLC.

VEGF and cortactin expression are independent predictors of tumor recurrence following curative resection of gastric cancer.

INTRODUCTION: To investigate the clinicopathological role of expression of vascular endothelial growth factor (VEGF) and cortactin, as well as whether their expression are independent predictors of tumor recurrence following curative resection of gastric cancer. METHODS: One hundred twenty-eight patients with gastric cancer were included in this study. Formalin-fixed paraffin-embedded specimens were stained for VEGF and cortactin, and the correlation between the staining, clinicopathological parameters and prognostic power were analyzed. RESULTS: Of the 128 patients studied, 58 (45.3%) and 71 (55.5%) cases were strongly positive for VEGF and cortactin, respectively. VEGF expression correlated with Lauren classification (P < 0.001), pathological tumor stage (P < 0.001), and pathological tumor node metastasis (TNM) stage (P = 0.003). Cortactin expression correlated with pathological lymph node stage (P = 0.018), pathological TNM stage (P < 0.001), and degree of differentiation (P < 0.001). There were statistically significant associations between tumor recurrence and VEGF expression (P = 0.023), and cortactin expression (P < 0.001). In multivariate analysis, pathological TNM stage, VEGF expression, and cortactin expression were independent prognostic influence on disease-free survival (P < 0.001, 0.022, and 0.034, respectively). CONCLUSIONS: VEGF and cortactin may be a good biomarker to be applied in clinic to predict the prognosis of patients with curatively resected gastric cancer.