TY - JOUR
T1 - Microsatellite instability and sex differences in resectable gastric cancer – A pooled analysis of three European cohorts
AU - Quaas, Alexander
AU - Biesma, Hedde D.
AU - Wagner, Anna D.
AU - Verheij, Marcel
AU - van Berge Henegouwen, Mark I.
AU - Schoemig-Markiefka, Birgid
AU - Pamuk, Aylin
AU - Zander, Thomas
AU - Siemanowski, Janna
AU - Sikorska, Karolina
AU - Egthuijsen, Jacqueline M. P.
AU - Meershoek-Klein Kranenbarg, Elma M.
AU - van de Velde, Cornelis J. H.
AU - Buettner, Reinhard
AU - Alakus, Hakan
AU - Cats, Annemieke
AU - Ylstra, Bauke
AU - van Laarhoven, Hanneke W. M.
AU - van Grieken, Nicole C. T.
N1 - Funding Information: MIvBH has served in a consultant or advisory role for Medtronic, Mylan, Alesi Surgical, Johnson and Johnson, BBraun, and received funding for research from Olympus, Stryker, all fees paid to the institution and unrelated to the present study. AC received grants form Dutch Cancer Society, Dutch Colorectal Cancer Group, Hofmann-La Roche, all fees paid to the institute and unrelated to the present study. HWMvL has served in a consultant or advisory role for BMS, Daiichy, Lilly, MSD, Nordic Pharma, Novartis, Servier, and received funding for research or study medication from Bayer, BMS, Celgene, Janssen, Lilly, Merck, Nordic Pharma, Philips, Roche, Servier, and received research funding from the Dutch Cancer Society, Dutch Research Council, European Research Council, MaagLeverDarm Stichting, all fees paid to the institution and unrelated to the present study. NCTvG has served on the advisory boards of BMS and MSD. Topics were unrelated to the present study. Funding Information: Parts of this study were supported by the Cancer Center Amsterdam and The Netherlands Organisation for Health Research and Development . Publisher Copyright: © 2022 The Author(s)
PY - 2022/9/1
Y1 - 2022/9/1
N2 - Objective: Biological sex differences in cancer are increasingly acknowledged. Here, we examined these differences in clinicopathological characteristics and survival in microsatellite instability (MSI)-high and microsatellite stable (MSS) gastric cancer (GC). Design: We analysed MSI status by polymerase chain reaction (PCR) and/or mismatch repair (MMR) status by immunohistochemistry in a pooled analysis of individual patient data from one retrospective cohort from Cologne, and the randomised phase III clinical trials D1/D2 and CRITICS. All patients had resectable adenocarcinoma of the stomach and/or gastro-oesophageal junction. Patients were treated with either surgery only or perioperative chemo(radio)therapy. Results: MSI and/or MMR analyses on 1307 tumours resulted in 1192 (91.2%) MSS and/or MMR proficient (MMRP) [median age, 65 years; 759 males (63.7%); 619 treated with surgery only (51.9%)], and 115 (8.8%) MSI-high [median age, 69 years; 67 males (58.3%); 76 treated with surgery only (66.1%)] GC cases. Males had shorter overall survival (OS) than female MSI-high GC (5-year OS 34.7% vs. 69.7%; hazard ratio (HR) 2.68, 95%CI 1.60 to 4.49; p < 0.001). Females with MSI-high had longer OS than those with MSS/MMRP GC (HR 0.61, 95%CI 0.41 to 0.92; p = 0.02). Males with MSI-high did not have longer OS than those with MSS/MMRP GC (HR 1.26, 95%CI 0.94 to 1.69; p = 0.12). Conclusions: MSI-high GC males had a significantly worse prognosis compared to their female counterparts in three independent cohorts. In addition, the favourable prognostic value of MSI was only seen in females and not in males. These observations emphasise the need to consider sex differences in prognosis and treatment effects in oncology. Clinical trial registration: The CRITICS trial is registered at ClinicalTrials.gov, number NCT00407186; EudraCT, number 2006-004130-32; and CKTO, 2006-02.
AB - Objective: Biological sex differences in cancer are increasingly acknowledged. Here, we examined these differences in clinicopathological characteristics and survival in microsatellite instability (MSI)-high and microsatellite stable (MSS) gastric cancer (GC). Design: We analysed MSI status by polymerase chain reaction (PCR) and/or mismatch repair (MMR) status by immunohistochemistry in a pooled analysis of individual patient data from one retrospective cohort from Cologne, and the randomised phase III clinical trials D1/D2 and CRITICS. All patients had resectable adenocarcinoma of the stomach and/or gastro-oesophageal junction. Patients were treated with either surgery only or perioperative chemo(radio)therapy. Results: MSI and/or MMR analyses on 1307 tumours resulted in 1192 (91.2%) MSS and/or MMR proficient (MMRP) [median age, 65 years; 759 males (63.7%); 619 treated with surgery only (51.9%)], and 115 (8.8%) MSI-high [median age, 69 years; 67 males (58.3%); 76 treated with surgery only (66.1%)] GC cases. Males had shorter overall survival (OS) than female MSI-high GC (5-year OS 34.7% vs. 69.7%; hazard ratio (HR) 2.68, 95%CI 1.60 to 4.49; p < 0.001). Females with MSI-high had longer OS than those with MSS/MMRP GC (HR 0.61, 95%CI 0.41 to 0.92; p = 0.02). Males with MSI-high did not have longer OS than those with MSS/MMRP GC (HR 1.26, 95%CI 0.94 to 1.69; p = 0.12). Conclusions: MSI-high GC males had a significantly worse prognosis compared to their female counterparts in three independent cohorts. In addition, the favourable prognostic value of MSI was only seen in females and not in males. These observations emphasise the need to consider sex differences in prognosis and treatment effects in oncology. Clinical trial registration: The CRITICS trial is registered at ClinicalTrials.gov, number NCT00407186; EudraCT, number 2006-004130-32; and CKTO, 2006-02.
KW - Gastric carcinoma
KW - Microsatellite instability (MSI-high)
KW - Prognosis
KW - Sex differences
UR - http://www.scopus.com/inward/record.url?scp=85134798119&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ejca.2022.06.025
DO - https://doi.org/10.1016/j.ejca.2022.06.025
M3 - Article
C2 - 35863110
SN - 0959-8049
VL - 173
SP - 95
EP - 104
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -