Hourin Cho1, Masayoshi Yamada2, Shigeki Sekine3, Noriko Tanabe4, Mineko Ushiama4,5, Makoto Hirata4, Gakuto Ogawa6, Masahiro Gotoh5, Teruhiko Yoshida4, Takaki Yoshikawa7, Yutaka Saito1, Aya Kuchiba6, Ichiro Oda1, Kokichi Sugano4,8. 1. Endoscopy Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 2. Endoscopy Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. masyamad@ncc.go.jp. 3. Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 4. Department of Genetic Medicine and Services, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 5. Department of Clinical Genomics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 6. Biostatistics Division, Center for Research Administration and Support, National Cancer Center, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 7. Department of Gastric Surgery, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 8. Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Abstract
BACKGROUND: Although gastric cancer is one of the Lynch syndrome (LS)-related tumors, the clinicopathological features of gastric cancer in patients with LS remain uncertain. To investigate the incidence risk and clinicopathological features of gastric neoplasms in LS, we conducted a retrospective cohort study in Japanese LS patients. METHODS: LS patients with pathogenic mismatch repair (MMR) gene variants were extracted from the LS registry of the National Cancer Center Hospital, Japan. Cumulative risks of gastric neoplasm, including dysplasia and cancer, were estimated using the Kaplan-Meier method. Gastric atrophy was evaluated endoscopically and/or histologically. Immunohistochemical staining for MMR proteins was performed for all available specimens. RESULTS: Of 118 eligible patients, 26 patients were diagnosed with 58 gastric neoplasms. The cumulative incidence of gastric neoplasm was 41.0% (95% confidence interval, 26.9-55.0) at the age of 70. Of these, 13 (50%) patients developed synchronous and/or metachronous multiple gastric neoplasms. Among the 49 gastric neoplasms available for detailed pathological evaluation, all were associated with intestinal metaplasia. Immunohistochemically, 42 (86%) were MMR-deficient. The individuals with gastric atrophy had a significantly higher risk of developing gastric neoplasms compared with those without gastric atrophy (26 cases/54 individuals vs. 0 cases/53 individuals) (P = 0.026). CONCLUSION: LS patients, particularly those with atrophic gastritis, are at high risk of gastric neoplasm and often develop multiple tumors. Endoscopic surveillance for gastric cancer is recommended for LS patients, especially those with atrophic gastritis.
BACKGROUND: Although gastric cancer is one of the Lynch syndrome (LS)-related tumors, the clinicopathological features of gastric cancer in patients with LS remain uncertain. To investigate the incidence risk and clinicopathological features of gastric neoplasms in LS, we conducted a retrospective cohort study in Japanese LS patients. METHODS: LS patients with pathogenic mismatch repair (MMR) gene variants were extracted from the LS registry of the National Cancer Center Hospital, Japan. Cumulative risks of gastric neoplasm, including dysplasia and cancer, were estimated using the Kaplan-Meier method. Gastric atrophy was evaluated endoscopically and/or histologically. Immunohistochemical staining for MMR proteins was performed for all available specimens. RESULTS: Of 118 eligible patients, 26 patients were diagnosed with 58 gastric neoplasms. The cumulative incidence of gastric neoplasm was 41.0% (95% confidence interval, 26.9-55.0) at the age of 70. Of these, 13 (50%) patients developed synchronous and/or metachronous multiple gastric neoplasms. Among the 49 gastric neoplasms available for detailed pathological evaluation, all were associated with intestinal metaplasia. Immunohistochemically, 42 (86%) were MMR-deficient. The individuals with gastric atrophy had a significantly higher risk of developing gastric neoplasms compared with those without gastric atrophy (26 cases/54 individuals vs. 0 cases/53 individuals) (P = 0.026). CONCLUSION: LS patients, particularly those with atrophic gastritis, are at high risk of gastric neoplasm and often develop multiple tumors. Endoscopic surveillance for gastric cancer is recommended for LS patients, especially those with atrophic gastritis.
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Authors: Hans F A Vasen; Ignacio Blanco; Katja Aktan-Collan; Jessica P Gopie; Angel Alonso; Stefan Aretz; Inge Bernstein; Lucio Bertario; John Burn; Gabriel Capella; Chrystelle Colas; Christoph Engel; Ian M Frayling; Maurizio Genuardi; Karl Heinimann; Frederik J Hes; Shirley V Hodgson; John A Karagiannis; Fiona Lalloo; Annika Lindblom; Jukka-Pekka Mecklin; Pal Møller; Torben Myrhoj; Fokko M Nagengast; Yann Parc; Maurizio Ponz de Leon; Laura Renkonen-Sinisalo; Julian R Sampson; Astrid Stormorken; Rolf H Sijmons; Sabine Tejpar; Huw J W Thomas; Nils Rahner; Juul T Wijnen; Heikki Juhani Järvinen; Gabriela Möslein Journal: Gut Date: 2013-02-13 Impact factor: 23.059