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<p>KRAS G12C-mutated non-small cell lung carcinoma (NSCLC), caused by a glycine-to-cysteine substitution at codon 12, is associated with poor prognosis and is now targetable with specific inhibitors. We retrospectively analyzed 279 KRAS G12C-mutated NSCLC cases (2017–2023) from our registry with available histologic, immunohistochemical, and molecular data. The cohort included 279 patients (125 females, 151 males; mean age 67&#xa0;years, range 29–91). Most tumors were primary lung carcinomas (n = 229, 82%), while 45 (16%) were metastatic at presentation. Morphologic evaluation was available in 240 tumors: 37% showed solid squamous cell carcinoma (SCC)-like features, 61% rhabdoid/plasmacytoid morphology, and 17% sarcomatoid features. Adenocarcinoma-associated patterns were present in 67 cases, often mixed, and focal solid growth occurred in 77%. TTF1, Napsin A, and CK7 were positive in 86%, 87%, and 98%, respectively, whereas squamous markers were infrequent (p40/p63 7%, CK5/6 8%). PD-L1 expression was detected in 65%. Co-mutations most commonly involved <i>TP53</i> (n = 27) and <i>STK11</i> (n = 12); <i>IDH1</i>/<i>2, PIK3CA</i>, and <i>CTNNB1</i> mutations occurred in four cases each, <i>MET</i> in two cases, and <i>BRAF</i>, <i>FGFR2</i>, <i>FGFR3</i>, and <i>GNAS</i> in one case each. Two gene fusions were identified (<i>LRP12</i>::<i>NRG1</i>, <i>FGFR3</i>::<i>TACC3</i>). Mean survival was 1.89&#xa0;years, with one- and five-year survival rates of 54% and 25%. KRAS G12C-mutated NSCLC is clinically aggressive and frequently shows solid growth with rhabdoid, plasmacytoid, or SCC-like morphology, which may lead to misclassification and missed genetic testing. Immunohistochemistry and molecular profiling are essential for accurate classification and enabling targeted therapy.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月15日

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  • Martina Bradová,
  • Petr Slavík,
  • Tomáš Vaněček,
  • Petr Martínek,
  • Petr Grossmann,
  • Stanislav Kormunda,
  • Kristýna Behenská,
  • Martin Svatoň,
  • Miloš Pešek,
  • Tomáš Jirásek,
  • Zuzana Špůrková,
  • Petra Hroudová,
  • Hana Mrázková,
  • Barbora Hořavová,
  • Jaromír Roubec,
  • Martin Baník,
  • Petr Mukenšnábl,
  • Michal Michal,
  • Marián Švajdler

摘要

KRAS G12C-mutated non-small cell lung carcinoma (NSCLC), caused by a glycine-to-cysteine substitution at codon 12, is associated with poor prognosis and is now targetable with specific inhibitors. We retrospectively analyzed 279 KRAS G12C-mutated NSCLC cases (2017–2023) from our registry with available histologic, immunohistochemical, and molecular data. The cohort included 279 patients (125 females, 151 males; mean age 67 years, range 29–91). Most tumors were primary lung carcinomas (n = 229, 82%), while 45 (16%) were metastatic at presentation. Morphologic evaluation was available in 240 tumors: 37% showed solid squamous cell carcinoma (SCC)-like features, 61% rhabdoid/plasmacytoid morphology, and 17% sarcomatoid features. Adenocarcinoma-associated patterns were present in 67 cases, often mixed, and focal solid growth occurred in 77%. TTF1, Napsin A, and CK7 were positive in 86%, 87%, and 98%, respectively, whereas squamous markers were infrequent (p40/p63 7%, CK5/6 8%). PD-L1 expression was detected in 65%. Co-mutations most commonly involved TP53 (n = 27) and STK11 (n = 12); IDH1/2, PIK3CA, and CTNNB1 mutations occurred in four cases each, MET in two cases, and BRAF, FGFR2, FGFR3, and GNAS in one case each. Two gene fusions were identified (LRP12::NRG1, FGFR3::TACC3). Mean survival was 1.89 years, with one- and five-year survival rates of 54% and 25%. KRAS G12C-mutated NSCLC is clinically aggressive and frequently shows solid growth with rhabdoid, plasmacytoid, or SCC-like morphology, which may lead to misclassification and missed genetic testing. Immunohistochemistry and molecular profiling are essential for accurate classification and enabling targeted therapy.