Clinical features of biliary tract cancer in Japanese individuals with Lynch syndrome

Nobuhiko Kanaya; Hideki Aoki; Toshiaki Morito; Fumitaka Taniguchi; Kunitoshi Shigeyasu; Chieko Tamura; Kokichi Sugano; Kiwamu Akagi; Hideyuki Ishida; Kohji Tanakaya

doi:10.21037/jgo-22-165

Clinical features of biliary tract cancer in Japanese individuals with Lynch syndrome

J Gastrointest Oncol. 2022 Oct;13(5):2532-2538. doi: 10.21037/jgo-22-165.

Authors

Nobuhiko Kanaya^{1

2}, Hideki Aoki¹, Toshiaki Morito^{3

4}, Fumitaka Taniguchi¹, Kunitoshi Shigeyasu^{1

5}, Chieko Tamura⁶, Kokichi Sugano⁷, Kiwamu Akagi⁸, Hideyuki Ishida⁹, Kohji Tanakaya¹

Affiliations

¹ Department of Surgery, Iwakuni Clinical Center, Yamaguchi, Japan.
² Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³ Department of Pathology, Iwakuni Clinical Center, Yamaguchi, Japan.
⁴ Department of Pathology, Kagawa Rosai Hospital, Kagawa, Japan.
⁵ Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁶ Medical Information & Genetic Counseling Division, FMC Tokyo Clinic, Tokyo, Japan.
⁷ Department of Genetic Medicine, Kyoundo Hospital, Sasaki Foundation, Tokyo, Japan.
⁸ Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
⁹ Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.

Abstract

Background: Biliary tract cancer (BTC) is a Lynch syndrome (LS)-associated cancer with a high mortality rate. This study aimed to clarify the clinical features of BTC in individuals with LS and to discuss its management.

Methods: We obtained data from genetically verified Japanese individuals with LS who were diagnosed at a single institution, between January 2003 and April 2021. Moreover, 21 individuals with sporadic BTC (n=15) and LS associated BTC (n=6) underwent microsatellite instability (MSI) testing.

Results: Among 92 individuals with LS, 6 individuals with MLH1 variants developed BTCs (10 lesions, male/female, 2:1). The median age at diagnosis of initial BTC was 69 years (range, 34-78 years). Histological examination revealed a predominance of differentiated adenocarcinoma (89%). Then, 2 individuals had multiple BTCs. All available 7 BTC lesions showed high-frequency of microsatellite instability (MSI-H). MLH1 carriers showed a 7.2% cumulative risk of BTC development at an age of 70 years. Five of the six individuals died of BTC.

Conclusions: MSI analysis could facilitate LS identification in individuals with BTC. Surveillance for BTC should be considered for MLH1 carriers in Japan.

Keywords: Lynch syndrome (LS); biliary tract cancer (BTC); cumulative risk; microsatellite instability (MSI); mismatch repair gene (MMR gene).