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

作者: Natasha Rekhtman , Daphne C Ang , Gregory J Riely , Marc Ladanyi , Andre L Moreira

DOI: 10.1038/MODPATHOL.2013.74

关键词:

摘要: 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 adenocarcinomas also have histopathological features is not well established. We tested 180 resected for EGFR high-sensitivity mass spectrometry-based genotyping (Sequenom) PCR-based sizing assays. All tumors were assessed the proportion standard histological patterns (lepidic, acinar, papillary, micropapillary, solid, mucinous), several other clinical parameters, TTF-1 expression immunohistochemistry. Among carcinomas, 63 (35%) had (KRAS+), 35 (19%) (EGFR+), 82 (46%) neither mutation (KRAS-/EGFR-). Solid growth pattern was significantly over-represented in KRAS+ carcinomas: mean±s.d. amount solid carcinomas 27±34% compared with 3±10% EGFR+ (P<0.001) 15±27% KRAS-/EGFR- (P=0.033) tumors. Furthermore, at least focal (≥20%) component more common (28/63; 44%) (2/35; 6%; P<0.001) (21/82; 26%; P=0.022) carcinomas. mucinous associated presence tumor-infiltrating leukocytes heavier history. non-mucinous non-solid patterns, particularly lepidic lack necrosis, cytological atypia, hobnail cytology, expression, never/light In conclusion, extended molecular clinicopathological analysis reveals novel association histology inflammatory cells expands on previously recognized morphological associations mutations. recently shown be strong predictor aggressive behavior adenocarcinomas, which may underlie unfavorable prognosis these

参考文章(56)
Gregory J. Riely, Marc Ladanyi, KRAS Mutations: An Old Oncogene Becomes a New Predictive Biomarker The Journal of Molecular Diagnostics. ,vol. 10, pp. 493- 495 ,(2008) , 10.2353/JMOLDX.2008.080105
Sjoerd Rodenhuis, Robert J. C. Slebos, Clinical significance of ras oncogene activation in human lung cancer. Cancer Research. ,vol. 52, pp. 2665- 2669 ,(1992)
Melissa L. Johnson, Camelia S. Sima, Jamie Chaft, Paul K. Paik, William Pao, Mark G. Kris, Marc Ladanyi, Gregory J. Riely, Association of KRAS and EGFR mutations with survival in patients with advanced lung adenocarcinomas Cancer. ,vol. 119, pp. 356- 362 ,(2013) , 10.1002/CNCR.27730
Antonio Lanzavecchia, Enrico Mihich, Douglas Hanahan, Fourteenth Annual Pezcoller Symposium: the novel dichotomy of immune interactions with tumors. Cancer Research. ,vol. 63, pp. 3005- 3008 ,(2003)
Ji-lin Guan, Wen-zhao Zhong, She-juan An, Jin-ji Yang, Jian Su, Zhi-hong Chen, Hong-hong Yan, Zhi-yong Chen, Zhi-min Huang, Xu-chao Zhang, Qiang Nie, Yi-long Wu, KRAS Mutation in Patients with Lung Cancer: A Predictor for Poor Prognosis but Not for EGFR-TKIs or Chemotherapy Annals of Surgical Oncology. ,vol. 20, pp. 1381- 1388 ,(2013) , 10.1245/S10434-012-2754-Z
Erik Thunnissen, Mary Beth Beasley, Alain C Borczuk, Elisabeth Brambilla, Lucian R Chirieac, Sanja Dacic, Douglas Flieder, Adi Gazdar, Kim Geisinger, Philip Hasleton, Yuichi Ishikawa, Keith M Kerr, Sylvie Lantejoul, Yoshiro Matsuno, Yuko Minami, Andre L Moreira, Noriko Motoi, Andrew G Nicholson, Masayuki Noguchi, Daisuke Nonaka, Giuseppe Pelosi, Iver Petersen, Natasha Rekhtman, Victor Roggli, William D Travis, Ming S Tsao, Ignacio Wistuba, Haodong Xu, Yasushi Yatabe, Maureen Zakowski, Birgit Witte, Dirk Joop Kuik, Reproducibility of histopathological subtypes and invasion in pulmonary adenocarcinoma. An international interobserver study Modern Pathology. ,vol. 25, pp. 1574- 1583 ,(2012) , 10.1038/MODPATHOL.2012.106
Ping Yang, Kimary Kulig, Jennifer M. Boland, Michele R. Erickson-Johnson, Andre M. Oliveira, Jason Wampfler, Aminah Jatoi, Claude Deschamps, Randolph Marks, Connie Fortner, Shawn Stoddard, Francis Nichols, Julian Molina, Marie-Christine Aubry, Hui Tang, Eunhee S. Yi, Worse Disease-Free Survival in Never-Smokers with ALK+ Lung Adenocarcinoma Journal of Thoracic Oncology. ,vol. 7, pp. 90- 97 ,(2012) , 10.1097/JTO.0B013E31823C5C32
Jenifer L. Marks, Stephen Broderick, Qin Zhou, Dhananjay Chitale, Allan R. Li, Maureen F. Zakowski, Mark G. Kris, Valerie W. Rusch, Christopher G. Azzoli, Venkatraman E. Seshan, Marc Ladanyi, William Pao, Prognostic and Therapeutic Implications of EGFR and KRAS Mutations in Resected Lung Adenocarcinoma Journal of Thoracic Oncology. ,vol. 3, pp. 111- 116 ,(2008) , 10.1097/JTO.0B013E318160C607
E Santos, D Martin-Zanca, E. Reddy, M. Pierotti, G Della Porta, M Barbacid, Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient Science. ,vol. 223, pp. 661- 664 ,(1984) , 10.1126/SCIENCE.6695174