Reproducibility of a Proposed Grading System for Lung Adenocarcinoma and Correlation with Molecular Alterations
JA Barletta, E Thunnissen, S Dacic, LR Chirieac. Brigham and Women's Hospital, Boston, MA; VU University Medical Center, Amsterdam, Netherlands; University of Pittsburgh School of Medicine, Pittsburgh, PA
Background: We previously described a prognostically significant grading system for lung adenocarcinoma that incorporated the percentage of solid growth pattern and the degree of cytologic atypia. The purpose of the current study was to assess interobserver reproducibility of our proposed grading system and correlate grade with molecular alterations.
Design: We studied two cohorts (104 and 197 patients) with lung adenocarcinomas treated at two institutions. All H&E slides of tumors were evaluated for the percentage of solid growth pattern and the degree of cytologic atypia. Based on previous analyses, tumor architecture was scored based on the percentage of solid growth pattern as 1=<80% solid growth or 2=>80% solid growth, and cytologic atypia was scored as 1=mild or moderate atypia with uniform nuclei or 2=severe atypia with bizarre, enlarged nuclei of varied sizes. The grading score was computed as the sum of the architecture and cytologic atypia scores (2=well differentiated [WD], 3=moderately differentiated [MD], 4=poorly differentiated [PD]). For cohort A, three pathologists reviewed the slides independently. For cohort B, the EGFR and KRAS mutation status was recorded. We calculated the interobserver reproducibility for cohort A and correlated the grade with the molecular alterations in cohort B.
Results: For cohort A, the percentage overall agreement for assessment of solid growth pattern was 88.5%, for cytologic atypia it was 82.1% and for grade it was 66.7%. In cohort B, 32 cases (16.2%) had EGFR mutations, 68 (34.5%) had KRAS mutations, and 97 (49.2%) lacked both EGFR and KRAS mutations. Grade was significantly correlated with molecular alterations (p=0.0003). For tumors with EGFR mutations, 19 cases (59.4%) were WD, 13 (40.6%) were MD, and none were poorly differentiated. For tumors with KRAS mutations, 43 cases (63.2%) were WD, 14 (20.6%) were MD, and 11 (16.2%) were PD. For cases lacking EGFR and KRAS mutations, 33 cases (34.0%) were WD, 47 (48.5%) were MD, and 17 (17.5%) were PD.
Conclusions: Our results indicate that there is good interobserver agreement among pathologists for this grading system. In addition, the differentiation based on this grading system correlates with molecular alterations.
Monday, March 22, 2010 1:30 PM
Platform Session: Section E, Monday Afternoon