Claudin-1 Protein Expression Is a Good Prognostic Factor in Non-Small Cell Lung Cancer, but only in Squamous Cell Carcinoma Cases

Abstract

The aim of the study was to investigate the correlation between claudin (CLDN) protein expression and clinicopathological parameters as well as survival in histological subtypes of non-small cell lung cancer. Archived surgical resection specimens of 137 pathologic stage I primary bronchial cancers including 49 adenocarcinomas of non-lepidic variants (ADC), 46 adenocarcinomas of lepidic variants (L-ADC), and 42 squamous cell carcinomas (SCC) were examined. Immunohistochemistry (IHC) using antibodies against CLDN1,-2,-3,-4,-7 proteins as well as semiquantitative estimation (IHC scores 0–5) were performed. Claudin IHC scores of L-ADC differed significantly from ADC (CLDN1: p = 0.009, CLDN2: p = 0.005, CLDN3: p = 0.004, CLDN4: p = 0.001, CLDN7: p < 0.001, respectively) and SCC (CLDN1: p < 0.001, CLDN3: p < 0.001, CLDN7: p < 0.001, respectively). Highly significant CLDN3-CLDN4 parallel expression could be demonstrated in ADC and L-ADC (p < 0.001 in both), which was not observed in SCC (p = 0.131). ADC and SCC showed no correlation with smoking, whereas in case of L-ADC heavier smoking correlated with higher CLDN3 expression (p = 0.020). Regarding claudin expression and survival, in SCC significant correlation could be demonstrated between CLDN1 IHC positivity and better survival (p = 0.038). In NSCLC as a whole, high CLDN2 expression proved to be a better prognostic factor when compared with cases where CLDN2 IHC score was 0–1 vs. 2–5 (p = 0.009), however, when analyzed separately, none of the histological subgroups showed correlation between CLDN2 expression and overall survival. The claudin expression pattern was significantly different not only between the SCC–ADC and SCC–L-ADC but also between the L-ADC and ADC histological subgroups, which strongly underlines that L-ADC represents a distinct entity within the ADC group. CLDN1 overexpression is a good prognostic factor in NSCLC, but only in the SCC subgroup. © 2016 Arányi Lajos Foundation