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Clinicopathologic features of KRAS G12C-mutated non-small cell lung carcinomas:insights from 279 retrospective cases

Martina Bradová1,2,3, Petr Slavík4,5, Tomáš Vaněček5

  • 1Charles University, Faculty Hospital Plzen, Department of Pathology, Faculty of Medicine in Plzen, Czech Republic, 1Charles University, University Hospital Plzen, Plzen, Czech Republic. bradova@biopticka.cz.

Virchows Archiv : an International Journal of Pathology
|April 15, 2026
PubMed

Insights

KRAS G12C-mutated non-small cell lung carcinoma (NSCLC) is aggressive and often shows unusual cell shapes, potentially leading to misdiagnosis. Accurate classification through immunohistochemistry and molecular profiling is crucial for effective targeted therapy.

Area of Science:

  • Oncology
  • Pulmonology
  • Genetics

Background:

  • KRAS G12C mutations in non-small cell lung carcinoma (NSCLC) are linked to poor prognosis.
  • Targeted therapies are emerging for KRAS G12C-mutated NSCLC.
  • Understanding the diverse morphology and molecular landscape of these tumors is critical.

Purpose of the Study:

  • To retrospectively analyze the clinicopathologic, immunohistochemical, and molecular features of KRAS G12C-mutated NSCLC.
  • To identify common morphologic patterns and co-mutations in this NSCLC subtype.
  • To evaluate survival outcomes and highlight the importance of accurate diagnosis for targeted therapy.

Main Methods:

  • Retrospective analysis of 279 KRAS G12C-mutated NSCLC cases (2017-2023).
  • Review of histologic, immunohistochemical (IHC), and molecular data.
  • Morphologic evaluation, IHC for specific markers (TTF1, Napsin A, CK7, p40, p63, CK5/6), PD-L1 expression assessment, and co-mutation profiling.

Main Results:

  • The cohort comprised 279 patients; most tumors were primary lung carcinomas.
  • Frequent non-adenocarcinoma-like morphologies were observed: 37% SCC-like, 61% rhabdoid/plasmacytoid, 17% sarcomatoid.
  • High positivity for adenocarcinoma markers (TTF1, Napsin A, CK7) and low positivity for squamous markers.
  • Common co-mutations included TP53 (27 cases) and STK11 (12 cases).
  • Mean survival was 1.89 years, with 1- and 5-year survival rates of 54% and 25%, respectively.

Conclusions:

  • KRAS G12C-mutated NSCLC is clinically aggressive with frequent solid growth and rhabdoid, plasmacytoid, or SCC-like morphology.
  • These features can lead to misclassification and missed genetic testing opportunities.
  • Immunohistochemistry and molecular profiling are essential for accurate diagnosis and guiding targeted treatment strategies.
Keywords:
AdenocarcinomaKRAS G12CLungMolecular geneticsNSCLCStatistics

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