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Cytomorphologic features of advanced lung adenocarcinomas tested for EGFR and KRAS mutations: A retrospective review of 50 cases
Author(s) -
Marotti Jonathan D.,
Schwab Mary C.,
McNulty Nancy J.,
Rigas James R.,
DeLong Peter A.,
Memoli Vincent A.,
Tsongalis Gregory J.,
Padmanabhan Vijayalakshmi
Publication year - 2013
Publication title -
diagnostic cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.417
H-Index - 65
eISSN - 1097-0339
pISSN - 8755-1039
DOI - 10.1002/dc.21749
Subject(s) - kras , epidermal growth factor receptor , pathology , medicine , exon , adenocarcinoma , mutation , cancer research , biology , cancer , colorectal cancer , gene , genetics
Associations between bronchioloalveolar carcinoma (BAC), mucinous differentiation, and epidermal growth factor receptor (EGFR) and KRAS mutations have been previously reported in studies of surgical specimens. We present the cytomorphology of lung adenocarcinomas, including metastases that were diagnosed by cytologic methods and the relationship to both EGFR and KRAS mutational status. We retrospectively reviewed the clinical and cytomorphologic features of 50 lung adenocarcinomas that were tested for both EGFR and KRAS mutations. Cytomorphologic features evaluated included cell size, architectural pattern, nucleoli, intranuclear cytoplasmic inclusions (INCI), mucin, necrosis, squamoid features, lymphocytic response, and histologic features of BAC differentiation. DNA was extracted from a paraffin‐embedded cell block or frozen needle core fragments. Exon 19 deletions and the L858R mutation in exon 21 of EGFR were detected using PCR followed by capillary electrophoresis for fragment sizing. KRAS mutational analysis was performed by real‐time PCR using a set of seven different Taqman(r) allelic discrimination assays to detect six mutations in codon 12 and one mutation in codon 13. Six cases (12%) showed EGFR mutations, 12 (24%) showed KRAS mutations, and 38 (62%) contained neither EGFR nor KRAS mutations. The majority of patients had stage IV disease (78%); 20 samples (40%) were from metastatic sites. The presence of prominent INCI ( P = 0.036), papillary fragments ( P = 0.041), and histologic features of BAC on paraffin block ( P = 0.039) correlated with the presence of EGFR mutations. The presence of necrosis ( P = 0.030), squamoid features (P = 0.048), and poorly differentiated tumors ( P = 0.025) were more likely to be identified in the KRAS positive group. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.