Clinical utility of diagnosing Lynch syndrome in gynecologic oncology: a joint statement from four Japanese academic societies

Sep 23, 2026

Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome marked by substantially increased risks of colorectal and gynecologic malignancies. Endometrial cancer can act as a sentinel cancer, positioning gynecologists and gynecologic oncologists for early recognition and long-term management. This joint statement from four Japanese academic societies explains the clinical utility of LS diagnosis in gynecologic oncology, including a tumor-first strategy using universal mismatch repair immunohistochemistry and/or microsatellite instability testing for actionable biomarkers. It summarizes impacts, synchronous and metachronous patterns, ovarian cancer prevalence, surgical implications, immune checkpoint relevance, fertility-preserving approaches, and guidance on surveillance and cascade testing with attention to implementation barriers and healthcare system support.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Introduction

Risk and gene-specific profiles

Tumor-first diagnostic paradigm and implementation

International Journal of Clinical Oncology (2026) 31:1742–1755 [https://doi.org/10.1007/s10147-026-03126-8](https://doi.org/10.1007/s10147-026-03126-8) SPECIAL ARTICLE Clinical utility of diagnosing Lynch syndrome in gynecologic oncology: a joint statement from four Japanese academic societies Shinya Sato1 · Kenta Masuda2 · Katsutoshi Oda3 · Takeshi Kuwata4 · Takeshi Nakajima5 · Masayoshi Yamada6 · Tatsuro Yamaguchi7 · Akira Hirasawa8 · Masaki Mandai9 · Kohji Tanakaya10 · Hideyuki Ishida11 · Takayuki Yoshino12 · Aikou Okamoto13 Received: 11 May 2026 / Accepted: 2 July 2026 / Published online: 11 July 2026 © The Author(s) 2026 Abstract Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome, associated with substantially increased risks of colorectal and gynecologic malignancies. Endometrial cancer may serve as a sentinel cancer for LS, placing gynecologists and gynecologic oncologists in a key position for early recognition and long-term management. This joint statement was developed through a multidisciplinary process involving the Japan Society of Gynecologic Oncology, the Japan Society of Clinical Oncology, the Japanese Society of Hereditary Tumors, and the Japanese Society for Cancer of the Colon and Rectum. It aims to clarify the clinical utility of diagnosing LS in gynecologic oncology within the Japanese healthcare system. We outline a tumor-first paradigm in which universal mismatch repair immunohistochemistry and/or microsatellite instability testing for endometrial cancer facilitates LS detection and provides actionable biomarkers for systemic therapy. This statement summarizes the clinical impact of LS diagnosis across gynecologic oncology. We highlight patterns of synchronous and metachronous malignancies and the prevalence of LS in ovarian cancer, particularly in endometrioid and clear–cell subtypes. We discuss surgical implications, including risk-reducing hysterectomy with bilateral salpingo-oophorectomy, consideration of concomitant gynecologic risk-reducing surgery during colorectal cancer resection, and individualized ovarian preservation in selected early-stage endometrial cancer or atypical endometrial hyperplasia. We also review the treatment relevance of deficient mismatch repair/microsatellite instability-high status for immune checkpoint inhibitors and emerging fertility-preserving approaches, and address surveillance, cascade testing for relatives, implementation barriers, and the need for multidisciplinary pathways and healthcare system–level support to ensure equitable access to genetic counseling and testing. Keywords Lynch syndrome · Endometrial cancer · Ovarian cancer · Mismatch repair · Microsatellite instability · Immune checkpoint inhibitor Introduction Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome caused by germline pathogenic variants in MLH1, MSH2, MSH6, or PMS2, or by 3′-end deletions of EPCAM that silence MSH2 . LS confers elevated lifetime risks of multiple malignancies, including colorectal, endometrial, and ovarian cancers, as well as cancers of the stomach, small intestine, hepatobiliary tract, pancreas, urinary tract (renal pelvis and ureter), brain, and skin [1, 2]. Although historically identified through families with colorectal cancer, endometrial cancer (EC) frequently precedes colorectal cancer in women and may be the first malignancy within a family, creating an opportunity for early screening or diagnosis and prevention [3] . In women, EC is the most common LS-associated malignancy, and ovarian cancer (OC) risk is also increased, particularly for endometrioid and clear-cell histologies [4] . Consequently, gynecologists and gynecologic oncologists play an important role in LS detection and management. Shinya Sato and Kenta Masuda: Co first authors. Extended author information available on the last page of the article Beyond risk assessment, LS status can define clinically meaningful subgroups within E

FAQs

Why is endometrial cancer considered a sentinel cancer for Lynch syndrome?

Endometrial cancer may frequently precede colorectal cancer in women and can be the first malignancy in a family, enabling earlier screening and diagnosis. It therefore places gynecologists in a key position for recognizing LS and initiating long-term management.

How does the statement support a tumor-first approach for LS detection?

It outlines testing newly diagnosed endometrial cancer for mismatch repair deficiency using universal immunohistochemistry and/or microsatellite instability testing. This both facilitates LS detection and yields biomarkers relevant to systemic therapy decisions.

What clinical and treatment considerations are discussed for confirmed LS in gynecologic oncology?

The statement addresses patterns of synchronous and metachronous malignancies, LS prevalence in ovarian cancer subtypes, surgical implications such as risk-reducing hysterectomy with bilateral salpingo-oophorectomy, and immune checkpoint inhibitor relevance for dMMR/MSI-H disease. It also covers surveillance, cascade testing for relatives, and barriers to implementation.

Sep 23, 2026

Uploaded by mieayamfan