Prognostic Impact of Major Receptor Tyrosine Kinase Expression in Gastric Cancer

• Published in: Annals of surgical oncology 2014-12, Vol.21 (Suppl 4), p.584-590
• Main Authors: Kurokawa, Yukinori, Matsuura, Nariaki, Kawabata, Ryohei, Nishikawa, Kazuhiro, Ebisui, Chikara, Yokoyama, Yuhki, Shaker, Mohammed Nouri, Hamakawa, Takuya, Takahashi, Tsuyoshi, Takiguchi, Shuji, Mori, Masaki, Doki, Yuichiro
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - chemistry; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Adult; Aged; Aged, 80 and over; Female; Gastrectomy; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Staging; Oncology; Prognosis; Proto-Oncogene Proteins c-kit - analysis; Receptor Protein-Tyrosine Kinases - analysis; Receptor, Epidermal Growth Factor - analysis; Receptor, ErbB-2 - analysis; Receptors, Platelet-Derived Growth Factor - analysis; Retrospective Studies; Stomach Neoplasms - chemistry; Stomach Neoplasms - pathology; Stomach Neoplasms - surgery; Surgery; Surgical Oncology; Survival Rate; Translational Research and Biomarkers
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-014-3690-x

Background Various kinds of molecular targeted drugs to inhibit receptor tyrosine kinases (RTKs) have been recently developed. The relationship between the expression status of major RTKs and prognosis in gastric cancer remains unclear. We conducted a multicenter study to evaluate the prognostic impact of the expression of epidermal growth factor receptor (EGFR), c-Met, platelet-derived growth factor receptor (PDGFR), and c-Kit in gastric cancer. Methods This study included 153 gastric cancer patients who underwent gastrectomy at 9 institutions between 2000 and 2006. Expression status of EGFR, c-Met, PDGFR, and c-Kit were evaluated with immunohistochemistry (IHC) centrally. Overall survival based on RTK expression status was statistically compared. Cox multivariate analysis was conducted to adjust for potentially confounding factors. Results The positive rates for EGFR, c-Met, PDGFR, and c-Kit were 14.4, 24.8, 41.2, and 11.1 %, respectively. Significant interactions with expression status were observed for pathological N stage with EGFR; HER2-status with c-Met; tumor location, histology, and pathological N stage with PDGFR; and no examined variables with c-Kit. Concomitant HER2 positivity was observed for 0.7 % of tumors positive for EGFR, 3.9 % for c-Met, 4.6 % for PDGFR, and 1.3 % for c-Kit. There were some differences in overall survival between patients with or without RTK expression, but only c-Kit expression showed a significant survival difference in Cox multivariate analysis ( P  = 0.046). Conclusions Our multicenter study indicated that IHC expression of 4 RTKs had some prognostic impact and that c-Kit–positive status may be a significant indicator of good prognosis in gastric cancer patients.