Journal
EUROPEAN JOURNAL OF CANCER
Volume 49, Issue 11, Pages 2494-2503Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2013.04.003
Keywords
Biomarker; Chemotherapy; ERCC1; TUBB-3; Ki-67; RRM1; EGFR; Thymidylate synthase; NSCLC; Immunohistochemistry
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Funding
- Danish Cancer Research Foundation
- Arvid Nillsons Foundation
- Torben and Alice Frimodts Foundation
- Aase and Ejnar Danielsens Foundation
- Eva and Henry Fraenkels Foundation
- Danish Research Foundation
- Snedkermester Sophus Jacobsen and Hustru Astrid Jacobsens Foundation
- Foundation for the Promotion of Medical Cancer Treatment
- Research Foundation of the Department of Oncology, Rigshospitalet, Denmark
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Background: Prognostic 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 Methods: Immunohistochemical evaluation of the expression of excision repair cross complementation group 1 (ERCC1), epidermal growth factor receptor (EGFR), class III-beta-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. Results: Clinically 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. Conclusion: Most 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). (c) 2013 Elsevier Ltd. All rights reserved.
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