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Cited by 117Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentLung Cancer Research Studies

KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma

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Rekhtman, Natasha, Ang, Daphne C, Riely, Gregory J, Ladanyi, Marc, Moreira, Andre L·2013·Modern Pathology
DOI 10.1038/modpathol.2013.74PMC PMC3732528
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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.

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  • KRAS-mutant LUADs show dual propensity for either solid growth with NKX2-1 positivity or invasive mucinous adenocarcinoma histology with lack of NKX2-1 expression.

    “KRAS-mutant lung adenocarcinomas (LUADs) demonstrate dual propensity towards either solid growth pattern with positivity for the NKX2–1 homeobox transcription factor (also known as TTF1) or, alternatively, invasive mucinous adenocarcinoma histology and corresponding lack of NKX2–1 expression33.”

    From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [33]

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Authors
Rekhtman, N., Ang, D. C., Riely, G. J., Ladanyi, M., & Moreira, A. L.
Affiliations
Memorial Sloan Kettering Cancer Center (US)
Corresponding author
Rekhtman, Natasha
ORCID
Venue
Modern Pathology
Publisher
Elsevier BV
Published
2013-10
Volume
26
Issue
10
Pages
1307-1319
ISSN
0893-3952 (ISSN-L)
DOI
10.1038/modpathol.2013.74
PMC
PMC3732528
OpenAlex
W1966467711
Cited by
117
References
57
Citations by year
2026: 5 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 8 · 2017: 10 · 2016: 16 · 2015: 14 · 2014: 15 · 2013: 3
FWCI
13.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Modern Pathology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (CA129243)
  • National Cancer Institute (P01CA129243)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords
KRAS mutation, EGFR mutation, lung adenocarcinoma, solid growth pattern, tumor-infiltrating leukocytes, histological patterns, mucinous carcinoma, smoking history, anti-EGFR therapy resistance, molecular subtypes, lobectomy, lobectomy complications
MeSH terms
Adenocarcinoma, Adult, Aged, Aged, 80 and over, Female, Humans, Leukocytes, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Invasiveness, Proto-Oncogene Proteins, Proto-Oncogene Proteins p21(ras), ras Proteins, ErbB Receptors

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