ERCC1, BRCA1, thymidylate synthase (TS), class III beta tubulin (bTubIII), p53R2, RRM2 immunohistochemical expression in stage I-III non-small cell lung cancer (NSCLC): A tissue microarray (TMA) study.

Abstract

e21094 Background: previous studies have shown that high levels of BRCA1, TS and bTubIII and low levels of ERCC1 and RRM1 expression are associated with poor prognosis in NSCLC patients (pts) treated with surgery alone. Also, clinical studies suggest that ERCC1, RRM1, BRCA1 and bTubIII expression is associated with resistance to several agents. Methods: tumor tissue samples from 82 pts with stage I-III NSCLC who underwent surgery between 7/2005-3/2007 were analyzed. Viable tumor was sampled in triplicate for TMA analysis and slides were stained by immunohistochemistry (IHC) with antibodies against ERCC1, BRCA1, TS, bTubIII, P53R2, RRM2. All tissue arrays were examined and independently scored by two observers (M.T. and S.S.), blinded to the patients. The score was calculated using the following formula: (1 + I) × PC, where I represents the staining intensity and PC represents the percentage of tumor cells that stained at each intensity, respectively. A categorical value (positive vs negative) was used for statistical analyses of marker expression. In addition, IHC expression profiles were correlated with clinicopathological features. Results: during a median follow-up time of 41 months (range 28-54), a total of 13 deaths was observed. In univariate analysis, P53R2 expression was significantly higher in adenocarcinoma compared to squamous samples (mean score 59.3 vs 4, p = 0.01), whereas TS expression was significantly higher in squamous tumors (mean score 39.2 vs 3.1, p = 0.03). bTubIII expression was significantly higher in stage I vs stage II pts (mean score 200.2 vs 49.2, p = 0.023). No significant association was seen between ERCC1, BRCA1, RRM2 expression and any clinicopathological features. The small number of deaths is insufficient for meaningful prognostic evaluation. Conclusions: this study confirms the different expression of TS in adenocarcinoma compared to squamous pts and suggests a possible role of p53R2 as a marker for histological differentiation. The significantly higher expression of bTubIII in stage I compared to stage II pts may explain a stage-specific different efficacy of adjuvant chemotherapy. No significant financial relationships to disclose.