Correlation of a Proposed Scoring System for Lung Adencoarcinoma with Molecular Alterations.
Veronica E Klepeis, Eugene J Mark, Dora Dias-Santagata, A John Iafrate, Mari Mino-Kenudson. Massachusetts General Hospital, Boston
Background: A myriad of proposed revisions to the classification of lung adenocarcinomas, which often show heterogenous morphology, have attempted to tighten the correlation between histology and prognosis, and supplementation of histology by molecular markers may prove necessary. Recently, a three-tiered histologic pattern-based scoring system was developed for stage I lung adenocarcinomas which stratified patients into low, intermediate, and high-risk categories for disease recurrence (Sica G, et al. AJSP 2010). The aim of the current study was to correlate score with molecular alterations.
Design: One-hundred and thirty two lung adenocarcinomas including 80 stage I tumors surgically resected and submitted for molecular testing were classified based on the three tier histopathologic scoring system. Briefly, comprehensive histologic subtyping was performed in a semiquntitative manner with the percentage of the 5 possible histologic subtypes quantified in 10% increments. A BAC pattern was classified as Grade I, acinar and papillary patterns as Grade II and solid, micropapillary and the other variants as grade III. A score was then obtained for each tumor by adding together the 2 most predominant grades. For mutational analysis of each scored tumor, 110 described mutations of 13 genes were studied using mutiplex PCR. The association between score and tumor genotype was evaluated.
Results: While EGFR (37/132) or K-ras mutations (42/132) were detected in 60% of the tumors studied, 36% showed no detectable mutations. The association of EGFR mutants with a low-risk category (score 2 or 3) was statistically significant compared to the other molecular alterations (p = 0.044 for the entire cohort, p=0.0087 for the stage I).
|EGFR||18 (49%)||6 (16%)||13 (35%)||37|
|KRAS||12 (29%)||9 (21%)||21 (50%)||42|
|PIK3CA||1 (50%)||1 (50%)||0||2|
|None||15 (32%)||16 (34%)||16 (34%)||47|
|EGFR||13 (68%)||2 (11%)||4 (21%)||19|
|KRAS||10 (36%)||8 (25%)||11 (39%)||29|
|None||10 (36%)||13 (46%)||5 (18%)||28|