Impact of microsatellite status in early-onset colonic cancer
REACCT Collaborative, Alexandra Zaborowski, Ahmed Abdile. Michel Adamina, Felix Aigner, Laura d’Allens, Caterina Allmer, Andrea Álvarez, Rocío Anula, Mihailo Andric, Sam Atallah Simon Bach, Miklosh Bala, Marie Barussaud, Augustinas Baušys, Andrew D. Beggs, Felipe Bellolio, Melissa-Rose Bennett, Anton Berdinskikh, Vicki Bevan, Sebastiano Biondo, Gabriele Bislenghi, Marc Bludau, Nelleke P.M. Brouwer, Carl J. Brown, Christiane J. Bruns, Daniel D. Buchanan, Pamela Buchwald, Jacobus W. A. Burger, Никита Бурлов, Michela Campanelli, Maylis Capdepont, Michele Carvello, Hwee-Hoon Chew, Dimitri Christoforidis, David A. Clark, Marta Climent, Rowan Collinson, Kyle G. Cologne, Tomás Contreras, Roland S. Croner, I. R. Daniels, Giovanni Dapri, Justin Davies, Paolo Delrio, Quentin Denost, Michael Deutsch, André Roncon Dias, André D’Hoore, E. S. Drozdov, Daniel Duek, Malcolm G. Dunlop, Adam Dziki, Aleksandra Edmundson, Sergey Efetov, Alaa El‐Hussuna, Brodie Elliot, Sameh Hany Emile, Eloy Espín, Martyn Evans, Seraina Faes, Omar Faiz, Nuno Figueiredo, Fergal J. Fleming, Caterina Foppa, G Fowler, Matteo Frasson, Tim Forgan, Frank Frizelle, Shamil Gadaev, José Gellona, Tamara Glyn, Goran Barisic, Emma Greenwood, Marianne G. Guren, Stephanie Guillon, Ida Gutlic, Dieter Hahnloser, Heather Hampel, Ann Hanly, Hirotoshi Hasegawa, Lene Hjerrild Iversen, Andrew Hill, James Hill, Jiří Hoch, Roel Hompes, Luis Hurtado, Fabiano Iaquinandi, Ugnė Imbrasaitė, Rumana Islam, Mehrenah D Jafari, Andrea Jiménez Salido, Marta Jiménez‐Toscano, Yukihide Kanemitsu, А. М. Карачун, Ahmer Karimuddin, Deborah S. Keller, Justin Kelly, Rory Kennelly, Gleb Khrykov, Peter Kocian, Cherry Koh
Abstract
BACKGROUND: The molecular profile of early-onset colonic cancer is undefined. This study evaluated clinicopathological features and oncological outcomes of young patients with colonic cancer according to microsatellite status. METHODS: Anonymized data from an international collaboration were analysed. Criteria for inclusion were patients younger than 50 years diagnosed with stage I-III colonic cancer that was surgically resected. Clinicopathological features, microsatellite status, and disease-specific outcomes were evaluated. RESULTS: A total of 650 patients fulfilled the criteria for inclusion. Microsatellite instability (MSI) was identified in 170 (26.2 per cent), whereas 480 had microsatellite-stable (MSS) tumours (relative risk of MSI 2.5 compared with older patients). MSI was associated with a family history of colorectal cancer and lesions in the proximal colon. The proportions with pathological node-positive disease (45.9 versus 45.6 per cent; P = 1.000) and tumour budding (20.3 versus 20.5 per cent; P = 1.000) were similar in the two groups. Patients with MSI tumours were more likely to have BRAF (22.5 versus 6.9 per cent; P < 0.001) and KRAS (40.0 versus 24.2 per cent; P = 0.006) mutations, and a hereditary cancer syndrome (30.0 versus 5.0 per cent; P < 0.001; relative risk 6). Five-year disease-free survival rates in the MSI group were 95.0, 92.0, and 80.0 per cent for patients with stage I, II, and III tumours, compared with 88.0, 88.0, and 65.0 per cent in the MSS group (P = 0.753, P = 0.487, and P = 0.105 respectively). CONCLUSION: Patients with early-onset colonic cancer have a high risk of MSI and defined genetic conditions. Those with MSI tumours have more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers.