KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma Journal Article
| Authors: | Rekhtman, N.; Ang, D. C.; Riely, G. J.; Ladanyi, M.; Moreira, A. L. |
| Article Title: | KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma |
| Abstract: | KRAS mutations define a clinically distinct subgroup of lung adenocarcinoma patients, characterized by smoking history, resistance to EGFR-targeted therapies, and adverse prognosis. Whether KRAS-mutated lung adenocarcinomas also have distinct histopathological features is not well established. We tested 180 resected lung adenocarcinomas for KRAS and EGFR mutations by high-sensitivity mass spectrometry-based genotyping (Sequenom) and PCR-based sizing assays. All tumors were assessed for the proportion of standard histological patterns (lepidic, acinar, papillary, micropapillary, solid, and mucinous), several other histological and clinical parameters, and TTF-1 expression by immunohistochemistry. Among 180 carcinomas, 63 (35%) had KRAS mutations (KRAS+), 35 (19%) had EGFR mutations (EGFR+), and 82 (46%) had neither mutation (KRAS-/EGFR-). Solid growth pattern was significantly over-represented in KRAS+ carcinomas: the mean±s.d. for the amount of solid pattern in KRAS+ carcinomas was 27±34% compared with 3±10% in EGFR+ (P<0.001) and 15±27% in KRAS-/EGFR- (P=0.033) tumors. Furthermore, at least focal (≥20%) solid component was more common in KRAS+ (28/63; 44%) compared with EGFR+ (2/35; 6%; P<0.001) and KRAS-/EGFR- (21/82; 26%; P=0.022) carcinomas. KRAS mutations were also over-represented in mucinous carcinomas and were significantly associated with the presence of tumor-infiltrating leukocytes and heavier smoking history. EGFR mutations were associated with non-mucinous non-solid patterns, particularly lepidic and papillary, lack of necrosis, lack of cytological atypia, hobnail cytology, TTF-1 expression, and never/light smoking history. In conclusion, extended molecular and clinicopathological analysis of lung adenocarcinomas reveals a novel association of KRAS mutations with solid histology and tumor-infiltrating inflammatory cells and expands on several previously recognized morphological and clinical associations of KRAS and EGFR mutations. Solid growth pattern was recently shown to be a strong predictor of aggressive behavior in lung adenocarcinomas, which may underlie the unfavorable prognosis associated with KRAS mutations in these tumors. © 2013 USCAP, Inc. All rights reserved. |
| Keywords: | adenocarcinoma; ttf-1; lung; egfr; kras |
| Journal Title: | Modern Pathology |
| Volume: | 26 |
| Issue: | 10 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2013-10-01 |
| Start Page: | 1307 |
| End Page: | 1319 |
| Language: | English |
| DOI: | 10.1038/modpathol.2013.74 |
| PROVIDER: | scopus |
| PMCID: | PMC3732528 |
| PUBMED: | 23619604 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 November 2013" - "CODEN: MODPE" - "Source: Scopus" |
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