Comprehensive Molecular Profiling and Clinicopathological Characteristics of Gastric-Type Mucinous Carcinoma of the Uterine Cervix in Japanese Women

Gastric-type mucinous carcinoma (GAS) of the uterine cervix is the most common adenocarcinoma that develops independently of human papillomavirus infection; it is typically diagnosed at an advanced stage and has a poorer prognosis than usual-type endocervical adenocarcinoma. Few studies have examined the molecular profile of GAS, but genetic alterations in TP53 and STK11 have been repeatedly reported. We analyzed the clinicopathological characteristics and molecular profile of GAS. Fresh-frozen tissue specimens and formalin-fixed paraffin-embedded (FFPE) tissues from 13 patients with GAS treated between January 2000 and December 2020 were analyzed. We performed next-generation sequencing on eight fresh-frozen GAS specimens using the Cancer Hotspot Panel v2 (cases 1–8) and the FoundationOne companion diagnostic (F1CDx) assay on six FFPE samples (cases 8–13). Seventy-four genomic alterations were identified in 42 genes. In order of frequency, TP53, ATRX, CDKN2A, KRAS, APC, and STK11 were altered in at least three cases. Targetable genomic alterations were identified in all six patients’ specimens analyzed using the F1CDx assay. GAS harbors various genomic alterations associated with sustained activation of signaling pathways or cell cycle regulation in addition to abnormalities in TP53, and precision medicine based on molecular profiling will be necessary to overcome GAS.