title: Mutations in the STK11 gene characterize minimal deviation adenocarcinoma of the uterine cervix.
abstract: Minimal deviation adenocarcinoma (MDA) is a well-differentiated variant of mucinous adenocarcinoma of the uterine cervix and is found relatively infrequently in the general population. However, MDA is strongly associated with Peutz-Jeghers syndrome (PJS), a rare hereditary autosomal disorder characterized by benign hamartomatous polyposis in the gastrointestinal tract and mucocutaneous pigmentation. A serine threonine kinase gene, STK11, has been identified as the tumor suppressor gene responsible for the PJS. In this study we investigated the possible direct role of STK11 in the development of MDA of the uterine cervix. Eleven rare cases of mucinous MDA, not known to be associated with PJS, were screened for the presence of mutations in the STK11 gene by single-strand conformation polymorphism analysis of PCR-amplified DNA fragments. Subsequently our findings were confirmed with cloning and sequencing. As a control, 24 cases of endocervical adenocarcinomas of other histologic subtypes, with no family history of PJS (19 mucinous adenocarcinomas, 4 endometrioid adenocarcinomas, and 1 clear cell adenocarcinoma), 15 cases of squamous cell carcinomas of the uterine cervix, 5 cases of endocervical glands with pyloric gland metaplasia, and 2 deeply situated nabothian cysts were investigated. Somatic mutations of the STK11 gene were confirmed in 6 (55%) of the 11 mucinous MDAs and 1 (5%) of the 19 mucinous adenocarcinomas, but not in the 5 nonmucinous adenocarcinomas, the 15 squamous cell carcinomas, nor the 5 endocervical glands with gastric metaplasia. MDAs with the STK11 mutation had a significantly poorer prognosis than MDAs without the STK11 mutation (p = 0.039). A germline mutation of STK11 was detected in one PJS patient with mucinous adenocarcinoma of the uterine cervix. These results suggest that mutations in the STK11 gene may play an important role in the etiology of MDA of the uterine cervix and may distinguish this rare tumor from other common types of adenocarcinoma of the uterine cervix.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Faculty of Medicine, Osaka, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Kuragaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Enomoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ueno
authors.forename: Hongbo
authors.initials: H
authors.lastname: Sun
authors.forename: Masami
authors.initials: M
authors.lastname: Fujita
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nakashima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ueda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Wada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Murata
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toki
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
authors.forename: Shingo
authors.initials: S
authors.lastname: Fujii
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D017931:DNA Primers; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases