Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound-guided fine-needle aspiration specimens from patients with unresectable pancreatic cancer

Takeshi Ogura, Kenji Yamao, Kazuo Hara, Nobumasa Mizuno, Susumu Hijioka, Hiroshi Imaoka, Akira Sawaki, Yasumasa Niwa, Masahiro Tajika, Shinya Kondo, Tsutomu Tanaka, Yasuhiro Shimizu, Vikram Bhatia, Kazuhide Higuchi, Waki Hosoda, Yasushi Yatabe

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

Abstract

Background: Although recent reports indicate that K-ras mutation status is a biomarker that acts as a prognostic factor, only a few analyses of K-ras mutation subtypes have been published. In addition, there are no reports that analyze overall survival and prognostic factors according to K-ras mutation status and subtypes in only unresectable pancreatic cancer (PC) determined from tissues obtained by endoscopic ultrasound-guided fine-needle aspiration. Methods: We retrospectively analyzed 242 patients who were diagnosed as having unresectable PC with available histological diagnosis. Clinical data collected included sex, age, Eastern Cooperative Oncology Group performance status, carbohydrate antigen (CA) 19-9, primary tumor location, stage (local or metastatic) according to TNM staging, first-line chemotherapy, K-ras mutation status and subtypes (G12D, G12V, and G12R), and overall survival. We analyzed the negative prognostic factors for reduced overall survival in unresectable PC patients using these data. Results: From multivariate analysis, CA19-9 ≥1000 U/ml (hazard ratio [HR] 1.78, 95 % confidence interval [CI] 1.28-2.46, P < 0.01), metastatic stage (HR 2.26, 95 % CI 1.58-3.24, P < 0.01), and mutant-K-ras (HR 1.76, 95 % CI 1.03-3.01, P = 0.04) were negative prognostic factors, indicating a reduced survival. Among the patients who had K-ras mutation subtypes, CA19-9 ≥1000 U/ml (HR 1.65, 95 % CI 1.12-2.37, P < 0.01), metastatic stage (HR 2.12, 95 % CI 1.44-3.14, P < 0.01), and the presence of the G12D or G12R mutations (HR 1.60, 95 % CI 1.11-2.28) were negative prognostic factors for overall survival. Conclusions: K-ras mutation status and subtypes may be associated with survival duration in pancreatic cancer patients.

Original languageEnglish
Pages (from-to)640-646
Number of pages7
JournalJournal of Gastroenterology
Volume48
Issue number5
DOIs
Publication statusPublished - 01-05-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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