Molecular and Histological Changes in Post-Treatment Biopsies of Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Study

Abstract

Background

Recently, in advanced non-small cell lung cancer (NSCLC), standard chemotherapy was flanked by biological agents directed against genomic abnormalities, including EGFR and ALK alterations, that significantly improved patient outcome. Despite these achievements, tumour progression almost always occurs and a reassessment of the tumour genetic profile may contribute to modulating the therapeutic regimen. Resampling may provide tissue for additional tests to detect acquired resistance and/or new genetic alterations, but the currently available information is limited.

Patients and Methods

Histological and genetic reassessments of biopsy or surgical tissue samples from 50 non-squamous NSCLC patients before and after at least one systemic treatment were performed. EGFR, KRAS, BRAF, PIK3CA and HER2 mutations were sequenced, p.T790M was identified with real-time PCR, and ALK and MET genomic alterations by fluorescence in situ hybridization.

Results

Overall in baseline biopsies, 37/50 (74 %) tumours had genetic alterations, either single (52 %) or multiple (22 %). Among them, 16 were EGFR mutations and 6 ALK rearrangements. In the second tissue sampling, 54 % of cases had additional genomic changes, including newly acquired alterations (81 %) or losses (18 %). The commonest changes were MET amplification and p.T790M mutation. One case had a histological shift from adenocarcinoma to small cell carcinoma.

Conclusions

The remarkable number of molecular changes following systemic therapy and the genetic complexity of some cases underline the value of histological and molecular re-evaluation of lung cancer to tailor the most appropriate therapy during disease progression.

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Acknowledgments

This work was partially supported by a grant from the Fondazione Guido Berlucchi, Brescia (approved 24 April 2013) to M.P. and HEALTH-F2- 2010-258677-CURELUNG from the European Community’s Seventh Framework Program (FP7/2007-2013) to G.V.S.

S.V. is a Ph.D. fellow at the University of Turin, Doctorate School of Biomedical Sciences and Oncology.

Conflict of Interest

A.V.: honoraria from Cook Medical, AstraZeneca, Amgen, Eli Lilly, Roche, Mundipharma, Bristol Myers Squibb, Novartis; M.P.: honoraria from Eli Lilly, Novartis, Pfizer, Clovis Oncology; G.V.S.: honoraria from Eli Lilly, AstraZeneca, Pfizer, Roche, Clovis Oncology, Icon; S.N.: honoraria from Eli Lilly, Boehringer Ingelheim, Roche, AstraZeneca, MSD. S.V., L.R., T.V., I.R., M.B., S.I. and S.C. have no conflicts of interest to declare.

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Correspondence to M. Papotti.

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Vatrano, S., Righi, L., Vavalá, T. et al. Molecular and Histological Changes in Post-Treatment Biopsies of Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Study. Targ Oncol 11, 157–166 (2016). https://doi.org/10.1007/s11523-015-0383-8

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Keywords

  • Epidermal Growth Factor Receptor
  • Epidermal Growth Factor Receptor Mutation
  • Anaplastic Lymphoma Kinase
  • Crizotinib
  • Anaplastic Lymphoma Kinase Rearrangement