Correlation between Morphologic Phenotype and Genotype of Lung Adenocarcinoma Based on a New IASLC/ATS/ERS Classification with Nuclear Grading
Noriko Motoi, Seijiro Sato, Yuichi Saito, Hironori Ninomiya, Kengo Takeuchi, Yuichi Ishikawa. Cancer Institute, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan
Background: Recent advantages of molecular study reveal several subsets of lung adenocarcinoma (AdCa) with specific genetic alterations of receptor tyrosine kinase (RTK), including EGFR, ALK, RET and ROS, which are dramatically response to targeted inhibitors for rearranged RTK. The goal of this study is to evaluate the correlation between genetic alteration and histologic phenotype of lung AdCa.
Design: 319 surgically resected lung AdCa were examined genetic alterations of EGFR by Cycleave or direct sequencing, ALK by FISH and immunohistochemistry and KRAS by PCR-RFLP and direct sequencing methods. Resected materials were reviewed detail histologic findings, using HE-stained slides of whole tumor. Histologic predominant subtype of AdCa, based on a new IASLC/ATS/ERS classification, and nuclear grading were evaluated. Correlation between genetic alteration and histologic phenotypes was examined.
Results: Genetic alterations of this study were 150 EGFR, 44 ALK, 9 KRAS and 116 wild-type. EGFR mutated AdCa had 55.4% lepidic- (lep), 40% papillary- (pap), 2.6% of acinar- (aci) and 2% of solid- (sol) predominant subtypes. ALK AdCa had 20.5% of lep, 36.4% pap, 18.2% aci, 22.7% sol and 2.3% micropapillary predominant subtypes. Kras mutated AdCa were 44.4% pap, 33.3% aci and 22.2% sol. All wild type AdCa were 35.3% of lep, 53.4% pap, 5.2% aci- and 6% sol. Presence of mucinous cells were observed in 4.7, 90.9, 66.7, and 26.7% of EGFR, ALK, KRAS and wild type AdCa, respectively. EGFR and ALK showed lower nuclear grade compared to KRAS. In summary, the most common histologic phenotype of EGFR AdCa was lepidic-predominant, non-mucinous with low nuclear grade; ALK AdCa was papillary, mucinous with low nuclear grade, and KRAS was papillary, mucinous with high nuclear grade.
Conclusions: Our data suggested significant correlation between genotype and histologic phenotype. Although, it should be mentioned that we couldn't exclude any possibility of absence or presence of some specific genomic alteration based on histologic features.
Monday, March 4, 2013 1:00 PM
Poster Session II # 287, Monday Afternoon