Clinicopathological characterization of female genital tract cancers with STK11 alterations: redefining the spectrum beyond STK11 adnexal tumors.

STK11 mutation is rarely reported in gynecologic malignancies. In addition to STK11 adnexal tumors, STK11 mutation can also be detected in other common types. The present study aims to investigate the clinicopathologic and prognostic features of female genital tract cancers with STK11 alterations. The authors retrospectively analyzed 13 cases of female genital tract cancers with STK11 alterations that underwent surgical resection at a regional medical center between 2017 and 2024. These cases exhibited typical morphological features and did not meet the diagnostic criteria for STK11 adnexal tumors. Detailed clinical data were collected, and all slides were carefully reviewed. The immunohistochemical stains for mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) were performed. Sanger sequencing and quantitative reverse-transcription PCR were performed to verify the presence of germline mutations. The authors further collected a consecutive series of 50 STK11 wild-type ovarian cancer cases from the same period to investigate the impact of STK11 mutations on the prognosis of ovarian cancer. The cohort included six cases of ovarian high-grade serous carcinoma (6/13, 46.2%), four cases of ovarian clear cell carcinoma (4/13, 30.8%), one case of endometrial endometrioid carcinoma (1/13, 7.7%), one case of cervical squamous cell carcinoma (1/13, 7.7%), and one case of cervical adenocarcinoma (1/13, 7.7%). The identified STK11 mutation types included missense (7/13, 53.8%), splice-site (2/13, 15.4%), single nucleotide variant (2/13, 15.4%), frameshift (1/13, 7.7%), in-frame deletion (1/13, 7.7%), and copy number variant (1/13, 7.7%). Germline mutations were detected in seven cases, and somatic mutations in seven cases, with one case harboring both. Co-occurring mutations were frequent, most notably in TP53 (8/13, 61.5%), BRCA1/2 (5/13, 38.5%), ATM (3/13, 23.1%), and RAS (3/13, 23.1%). Five cases suffered recurrence, among which four harbored TP53 mutations. Survival analysis did not demonstrate a significant impact of STK11 mutations on progression-free survival or overall survival in patients with ovarian cancer. STK11 alterations can be detected in common female genital tract cancers with typical morphologic features. In such cases, STK11 may not represent the principal driver alteration. The biological significance of STK11 mutations and their potential implications for treatment warrant further investigation.