Dissecting Pulmonary Large-Cell Carcinoma by Targeted Next Generation Sequencing of Several Cancer Genes Pushes Genotypic-Phenotypic Correlations to Emerge

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
Giuseppe PelosiUgo Pastorino

Abstract

Little is known about genotypic and phenotypic correlations in undifferentiated large-cell carcinoma (LCC) of the lung. Thirty LCC were dissected by unsupervised targeted next generation sequencing analysis for 50 cancer-associated oncogenes and tumor suppressor genes. Cell differentiation lineages were unveiled by using thyroid transcription factor-1 (TTF1) for adenocarcinoma (ADC) and p40 for squamous cell carcinoma (SQC), dichotomizing immunohistochemistry (IHC) results for TTF1 as negative or positive (whatever its extent) and for p40 as negative, positive, or focal (if <10% of reactive tumor cells). Three LCC were wild type (all TTF1+/p40-), whereas the remaining 27 (90%) tumors had at least one gene mutation. Twenty-four cases featuring TTF1+/p40-, TTF1+/p40±, TTF1-/p40±, or TTF1-/p40- phenotypes comprised ATM, BRAF, CDKN2A, EGFR, ERBB4, FBXW7, FLT3, KRAS, NRAS, PIK3CA, PTPN11, RET, SMAD4, SMO, STK11, or TP53 mutations in keeping with ADC lineage, whereas three tumors showing TTF1-/p40+ phenotype harbored TP53 only and no ADC-related mutations in keeping with SQC lineage. Single, double, triple, quadruple, and quintuple mutations occurred in 16, 6, 2, 2, and 1 patient, respectively. The occurrence of three mutations or mo...Continue Reading

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Citations

Aug 16, 2016·Surgical Pathology Clinics·Lynette M Sholl
Sep 13, 2016·Expert Review of Respiratory Medicine·Giuseppe PelosiAngelica Sonzogni
May 26, 2017·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Anna KarlssonJohan Staaf
Jan 22, 2021·Virchows Archiv : an International Journal of Pathology·Jasna MetovicGiuseppe Pelosi
Feb 2, 2020·Surgical Pathology Clinics·Roberto Ruiz-Cordero, Walter Patrick Devine

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