Tissue-specific variability in protein expression of cytochrome P450 and glutathione S-transferase isoenzymes in non-small cell lung carcinoma.

Abstract

Earlier tissue-based studies report heterogeneous CYP and GST protein expression in non-small cell lung cancer (NSCLC), but simultaneous assessment of phase I and II enzymes in paired tumour and peripheral normal tissues remains limited and their expression patterns poorly characterised across the two major NSCLC histological subtypes, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC). To address these gaps, this retrospective study evaluated CYP1A1, CYP1B1, CYP2E1, GSTM1, GSTT1, and GSTP1 expression immunohistochemically in tumour and peripheral normal lung tissues of 50 patients with NSCLC, 27 of whom with AC and 23 with SCC. Cytoplasmic staining intensity was scored from 0 to 3. Tissue and subtype comparisons were performed using the Mann-Whitney U test, and associations with clinical variables were assessed using Spearman's rank correlation. CYP2E1 expression was significantly higher in tumour than in normal tissue in the combined NSCLC group and in both histological subtypes (p<0.05). CYP1A1 expression was higher in AC tumours than in normal tissue and SCC tumours (both p<0.05). GSTM1 expression was higher in tumour tissue in the combined NSCLC group and in the SCC subgroup and was also higher in SCC than in AC tumours (p<0.05). GSTT1 expression was higher in AC than SCC tumours (p<0.05). CYP1B1 and GSTP1 were highly expressed in both tissue compartments but showed no significant tumour-specific increase. CYP and GST isoenzymes therefore showed tissue- and subtype-dependent rather than uniform expression patterns in NSCLC. The differences observed in CYP2E1, CYP1A1, GSTM1, and GSTT1 suggest that AC and SCC may differ in xenobiotic metabolism and cellular defence, and that these isoenzymes may contribute to metabolic processes associated with NSCLC pathogenesis.