Impact of microsatellite status in early-onset colonic cancer
Authors:   REACCT Collaborative, Zaborowski Alexandra M. , Adamina Ahmed Abdile. Michel , Aigner Felix , d'Allens Laura , Allmer Caterina , Álvarez Andrea , Anula Rocio , Andric Mihailo , Bach Sam Atallah Simon , Bala Miklosh , Barussaud Marie , Bausys Augustinas , Beggs Andrew , Bellolio Felipe , Bennett Melissa-Rose , Berdinskikh Anton , Bevan Vicki , Biondo Sebastiano , Bislenghi Gabriele , Bludau Marc , Brouwer Nelleke , Brown Carl , Bruns Christiane , Buchanan Daniel D. , Buchwald Pamela , Burger Jacobus W.A. , Burlov Nikita , Campanelli Michela , Capdepont Maylis , Carvello Michele , Chew Hwee-Hoon , Christoforidis Dimitri , Clark David , Climent Marta , Collinson Rowan , Cologne Kyle G. , Contreras Tomas , Croner Roland , Daniels Ian R. , Dapri Giovanni , Davies Justin , Delrio Paolo , Denost Quentin , Deutsch Michael , Dias Andre , D’Hoore André , Drozdov Evgeniy , Duek Daniel , Dunlop Malcolm , Dziki Adam , Edmundson Aleksandra , Efetov Sergey , El-Hussuna Alaa , Elliot Brodie , Emile Sameh , Espin Eloy , Evans Martyn , Faes Seraina , Faiz Omar , Figueiredo Nuno , Fleming Fergal , Foppa Caterina , Fowler George , Frasson Matteo , Forgan Tim , Frizelle Frank , Gadaev Shamil , Gellona Jose , Glyn Tamara , Goran Barisic , Greenwood Emma , Guren Marianne G. , Guillon Stephanie , Gutlic Ida , Hahnloser Dieter , Hampel Heather , Hanly Ann , Hasegawa Hirotoshi , Iversen Lene Hjerrild , Hill Andrew , Hill James , Hoch Jiri , Hompes Roel , Hurtado Luis , Iaquinandi Fabiano , Imbrasaite Ugne , Islam Rumana , Jafari Mehrenah D , Salido Andrea Jiménez , Jiménez-Toscano Marta , Kanemitsu Yukihide , Karachun Aleksei , Karimuddin Ahmer A. , Keller Deborah S. , Kelly Justin , Kennelly Rory , Khrykov Gleb , Kocian Peter , Koh Cherry , Kok Neils , Knight Katrina A. , Knol Joep , Kontovounisios Christos , Korner Hartwig , Krivokapic Zoran , Kronberger Irmgard , Kroon Hidde Maarten , Kryzauskas Marius , Kural Said , Kusters Miranda , Lakkis Zaher , Lankov Timur , Larson David , Lázár György , Lee Kai-Yin , Lee Suk Hwan , Lefèvre Jérémie H. , Lepisto Anna , Lieu Christopher , Loi Lynette , Lynch Craig , Maillou-Martinaud Helene , Maroli Annalisa , Martin Sean , Martling Anna , Matzel Klaus E. , Mayol Julio , McDermott Frank , Meurette Guillaume , Millan Monica , Mitteregger Martin , Moiseenko Andrei , Monson John RT. , Morarasu Stefan , Moritani Konosuke , Möslein Gabriela , Munini Martino , Nahas Caio , Nahas Sergio , Negoi Ionut , Novikova Anastasia , Ocares Misael , Okabayashi Koji , Olkina Alexandra , Oñate-Ocaña Luis , Otero Jaime , Ozen Cihan , Pace Ugo , Julião Guilherme Pagin São , Panaiotti Lidiia , Panis Yves , Papamichael Demetris , Patel Swati , Uriburu Juan Carlos Patrón , Peng Sze-Lin , Pera Miguel , Perez Rodrigo O. , Petrov Alexei , Pfeffer Frank , Phang Terry P. , Poskus Tomas , Pringle Heather , Proud David , Raguz Ivana , Rama Nuno , Rasheed Shahnawaz , Raval Manoj J. , Rega Daniela , Reissfelder Christoph , Meneses Juan Carlos Reyes , Ris Frederic , Riss Stefan , Rodriguez-Zentner Homero , Roxburgh Campbell S , Saklani Avanish , Sammour Tarik , Saraste Deborah , Schneider Martin , Seishima Ryo , Sekulic Aleksandar , Seppala Toni , Sheahan Kieran , Shlomina Alexandra , Sigismondo Guiseppe , Singnomklao Tongplaew , Siragusa Leandro , Smart Neil , Solis-Peña Alejandro , Spinelli Antonino , Staiger Roxane D. , Stamos Michael J. , Steele Scott , Tan Ker-Kan , Tanis Pieter J , Tekkis Paris , Teklay Biniam , Tengku Sabrina , Tsarkov Petr , Turina Matthias , Ulrich Alexis , Vailati Bruna B. , van Harten Meike , Verhoef Cornelis , Warrier Satish , Wexner Steven , de Wilt Hans , Weinberg Benjamin A. , Wells Cameron , Wolthuis Albert , Xynos Evangelos , You Nancy , Zakharenko Alexander , Zeballos Justino , Zhou Jonathan , Winter Des C. 
Published: March 2022

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 &lt; 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 &lt; 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.