Intratumour variation of biomarker expression by immunohistochemistry in resectable non-small cell lung cancer

Abstract

BackgroundPrognostic and predictive biomarkers are increasingly used to customise the treatment of patients with solid tumours. Intra- and inter-tumour heterogeneous distribution of biomarker expression is a potential confounder for the use of biomarkers, as small biopsies may not necessarily truly reflect the pattern of biomarker expression. It may also be an important factor in chemo resistance, as tumours with heterogeneous biomarker expression may potentially harbour chemo resistant tumour clones. Materials and MethodsImmunohistochemical evaluation of the expression of excision repair cross complementation group 1 (ERCC1), epidermal growth factor receptor (EGFR), class III-β-tubulin (TUBB-3), thymidylate synthase (TS), Ki-67 and ribonucleotide reductase M1 (RRM1) was performed in 15 separate areas in each of six small microscopically completely resected adenocarcinomas of the lung in order to elucidate any heterogeneous distribution. ResultsClinically relevant biomarker heterogeneity with respect to the expression of EGFR, ERCC1, RRM1, TUBB-3 and Ki-67 was observed in four (66%), four (66%), one (16%), three (50%) and five (83%) out of six tumours, respectively. Thus, heterogeneity could potentially allocate these tumours erroneously into high or low expressers by chance alone, according to previously reported cut-off values. In contrast, TS was almost completely homogenously distributed. ConclusionMost biomarkers examined, except for TS, showed clinically significant intratumour heterogeneity in 33–87% of tumours examined. This heterogeneity may influence results in studies investigating the therapeutic impact of predictive biomarkers in non-small cell lung cancer (NSCLC).