Su Mi Kim1, Ji Yeong An2, Sun-Ju Byeon3, Jeeyun Lee4, Kyoung-Mee Kim3, Min-Gew Choi5, Jun Ho Lee5, Tae Sung Sohn5, Jae Moon Bae5, Sung Kim5. 1. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Surgery, CHA Bundang Hospital, CHA University School of Medicine, Seongnam, South Korea. 2. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: jar319.an@samsung.com. 3. Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 4. Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 5. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Abstract
OBJECTIVE: The predictive value of mismatch repair protein deficiency (MMRD) for chemoradiotherapeutic outcome has rarely been reported in gastric cancer. This study investigated the clinical significance of MMRD as a prognostic factor for tumor recurrence, and as a predictor of response to adjuvant chemoradiotherapy in advanced gastric cancer patients. METHODS: Between 1995 and 2008, tissue specimens of 881 patients who underwent radical gastrectomy for stage II and III gastric cancer were analyzed. MMRD was assessed using immunohistochemical stains for MLH1, PMS2, MSH2, and MSH6. Patients were divided into two groups according to adjuvant treatment: a 5-fluorouracil/leucovorin (FL) adjuvant chemoradiotherapy group and a surgery alone group. Disease-free survival (DFS) was compared between the two groups correlated to MMRD. Risk factors for tumor recurrence were analyzed using multivariate analysis. RESULTS: Of the 881 gastric cancer patients, 88 (10.0%) exhibited MMRD and 398 (45.2%) patients received adjuvant FL chemoradiotherapy. The multivariate analysis revealed that MMRD was a good independent prognostic factor (hazard ratio, 0.572; 95% confidence interval, 0.370-0.883; P = 0.012). For stage III gastric cancer displaying mismatch repair protein proficiency (MMRP), adjuvant FL chemoradiotherapy after surgery resulted in better DFS than surgery alone (P = 0.001). Among the stage II gastric cancer patients, adjuvant FL chemoradiotherapy did not show survival benefit, regardless of MMRD. CONCLUSION: MMRD is a good independent prognostic factor in advanced gastric cancer. Adjuvant FL chemoradiotherapy was beneficial in patients with stage III gastric cancer with MMRP but not in those with MMRD.
OBJECTIVE: The predictive value of mismatch repair protein deficiency (MMRD) for chemoradiotherapeutic outcome has rarely been reported in gastric cancer. This study investigated the clinical significance of MMRD as a prognostic factor for tumor recurrence, and as a predictor of response to adjuvant chemoradiotherapy in advanced gastric cancerpatients. METHODS: Between 1995 and 2008, tissue specimens of 881 patients who underwent radical gastrectomy for stage II and III gastric cancer were analyzed. MMRD was assessed using immunohistochemical stains for MLH1, PMS2, MSH2, and MSH6. Patients were divided into two groups according to adjuvant treatment: a 5-fluorouracil/leucovorin (FL) adjuvant chemoradiotherapy group and a surgery alone group. Disease-free survival (DFS) was compared between the two groups correlated to MMRD. Risk factors for tumor recurrence were analyzed using multivariate analysis. RESULTS: Of the 881 gastric cancerpatients, 88 (10.0%) exhibited MMRD and 398 (45.2%) patients received adjuvant FL chemoradiotherapy. The multivariate analysis revealed that MMRD was a good independent prognostic factor (hazard ratio, 0.572; 95% confidence interval, 0.370-0.883; P = 0.012). For stage III gastric cancer displaying mismatch repair protein proficiency (MMRP), adjuvant FL chemoradiotherapy after surgery resulted in better DFS than surgery alone (P = 0.001). Among the stage II gastric cancerpatients, adjuvant FL chemoradiotherapy did not show survival benefit, regardless of MMRD. CONCLUSION: MMRD is a good independent prognostic factor in advanced gastric cancer. Adjuvant FL chemoradiotherapy was beneficial in patients with stage III gastric cancer with MMRP but not in those with MMRD.
Authors: J Schumacher; P Malfertheiner; M Venerito; T Stolze; S Franke; J Haybaeck; M Moehler; P P Grimminger; H Lang; W Roth; I Gockel; N Kreuser; H Bläker; C Wittekind; F Lordick; M Vieth; L Veits; O Waidmann; P Lingohr; U Peitz; C Schildberg; M Kruschewski; N Vassos; E Goni; C J Bruns; K Ridwelski; S Wolff; H Lippert Journal: J Cancer Res Clin Oncol Date: 2022-02-25 Impact factor: 4.553