[416] Cytological and Immunohistochemical Features of EGFR and KRAS Positive Lung Adenocarcinomas: A Study of 51 Cases.

Vijayalakshmi Padmanabhan, Jonathan D Marotti, Mary C Schwab, Vincent A Memoli, Laura J Tafe, Gregory J Tsongalis. Dartmouth Hitchcock Medical Center, Lebanon, NH

Background: An association between mucinous bronchioloalveolar carcinoma (BAC) histologic features and EGFR and KRAS mutations has been reported in lung adenocarcinomas. However, many lung carcinomas are diagnosed using cytologic methods (FNA, cell block, touch imprint, needle core biopsy). Here we present the cytological heterogeneity and immunohistochemical features of lung adenocarcinomas and their relationship with EGFR and KRAS mutations
Design: We retrospectively reviewed the cytomorphological and immunohistochemical features of 51 lung cytology specimens that were previously tested for activating EGFR and KRAS mutations. Though BAC cannot reliably be diagnosed cytologically, features suspicious for BAC include bland mucinous epithelium, grooves and intranuclear pseudoinclusions. TTF-1 and cytokeratin immunostains were reviewed. DNA was extracted from archived paraffin-embedded cell block or frozen skinny needle core fragments. KRAS mutation analysis was performed on the 7500 Fast Real-Time PCR System (Applied Biosystems) using a set of 7 different TaqMan(r) allelic discrimination assays to detect 6 mutations in codon 12 (G12A, G12D, G12V, G12C, G12R, and G12S) and 1 mutation in codon 13 (G13D). Exon 19 deletions and the L858R mutation in exon 21 of EGFR were detected using PCR followed by capillary electrophoresis for fragment sizing on the CEQ 8000 platform (Beckman Coulter).
Results:

 EGFR+/KRAS-EGFR-/KRAS+EGFR+/KRAS+EGFR-/KRAS-
n (%)6 (12)11 (21.5%)1 (<1)33 (64%)
Adenocarcinoma differentiation
Well3/6 (50%)002/33 (6%)
Moderate01/11 (9%)09/33 (27%)
Poor3/6 (50%)7/11 (64%)016/33 (48%)
NSCCa, poorly differentiated03/11 (27%)1 (100%)6/33 (18%)
TTF-16/6 (100%)11/11 (100%)not done22/31 (71%)
BAC- features1/6 (17%)003/33 (19%)
Mucin2/6 (33%)5/11 (45%)015/33 (15%)



Conclusions: The majority of carcinomas with KRAS mutations were poorly differentiated (91%), whereas tumors with EGFR mutations were both well-differentiated (50%) and poorly differentiated (50%) adenocarcinomas. Mucin present in cases with KRAS mutations was predominantly in the form of intracytoplasmic lumina and/ or extracellular mucin associated with poorly differentiated cells. In previous studies, mucinous BAC- type differentiation correlated with the absence of EGFR mutation and presence of KRAS mutation; a finding that was not seen in this study. Further studies are warranted to correlate cytological findings with EGFR and KRAS mutations.
Category: Cytopathology

Tuesday, March 1, 2011 9:30 AM

Poster Session III # 84, Tuesday Morning

 

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