Molecular Histologic Correlations in the Cancer Genome Atlas (TCGA) Study of Lung Squamous Cell Carcinoma (SQC)
William D Travis, Natasha Rekhtman, Ronglai Shen, Eunhee S Yi, Marie C Aubry, Richard Cheney, Sanja Dacic, Douglas Flieder, William Funkhouser, Peter Illei, Jerome Myers, Ming Sound Tsao, Matthew Wilkerson, Peter Hammerman, Ramaswamy Govindan, Neil Hayes, Matthew Meyerson. Memorial Sloan Kettering, New York, NY; Mayo Clinic, Rochester, MN; Roswell Park, Buffalo, NY; Univ of Pittsburgh, Pittsburgh, PA; Fox Chase Cancer Center, Philadelphia, PA; Univ of North Carolina, Chapel Hill; Johns Hopkins, Baltimore, MD; Penrose-St. Francis Health Services, Colorado Springs, CO; Princess Margaret Hospital, Toronto, ON, Canada; Dana Farber Cancer Institute, Boston, MA; Washington University, St. Louis, MO
Background: Most recent advances in molecular understanding of lung cancer are with adenocarcinoma (ADC). Little is known about the genetics of SQC. We report a major genetic analysis of SQC by the TCGA with histologic correlations.
Design: 213 tumors were submitted as squamous cell carcinomas to the TCGA for analysis. All of these were studied for copy number, LOH analysis, expression profiling, miRNA sequencing & methylation analysis. An expert pathology committee was formed to review the tumors to determine if they were SQC or other histologies. SQC & probable SQC cases were subclassified into keratinizing (K), nonkeratinizing (NK) & basaloid (B) subtypes. Histology was correlated with molecular findings. Immunostaining (IHC) for TTF-1, p63 & neuroendocrine markers helped reclassify a subset of problem cases.
Results: 177 SQC (157 definite, 20 probable) were separated from ADC (3), non-small cell carcinoma NOS (28), large cell neuroendocrine carcinoma (3), large cell carcinoma (1), & carcinoid (1). 29 of the 177 SQC were keratinizing (16%), 122 were nonkeratinizing (69%) & 26 were basaloid (15%). All cases found to have canonical EGFR and KRAS mutations were excluded by pathology review & none were present in SQC. Possible molecular therapeutic targets were identified in over 60% of cases including cyclin dependent kinases, fibroblast growth factor receptor mutations & amplifications & PI3 kinase pathway alterations. According to previously published mRNA expression categories the histologic subtypes (K:NK:B) were: 9 (8%) primitive (K:78%; B:22%); 48 (44%) classical (K:13%,NK:75%, B:12%); 17 (16%) secretory (K:18%, NK:59%, B:23%) and 34 (32%) basal (K:24%, NK:67%, B:9%).
Conclusions: As seen with the 17% reclassified tumors, the distinction between SQC & ADC has evolved substantially in recent years & it will become increasingly important as molecular targeted therapies become available for SQC as well as ADC. Even in resected tumors, there are problem cases that require IHC to make an accurate diagnosis.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 292, Tuesday Morning