Hereditary gynecological tumors associated with Peutz-Jeghers syndrome (Review)

Abstract

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that is characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin spots. The tumor suppressor gene, STK11/LKB1, which is located on chromosome 19p13.3, has been reported to be responsible for this condition. PJS is complicated by benign and malignant tumors of various organs and complications from rare diseases, including sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which have also recently attracted attention in the field of gynecology. Among the total MDA cases, 10% are complications of PJS, and mutations in the STK11 gene are closely associated with the development and prognosis of MDA. Furthermore, a new type of uterine cervical tumor, lobular endocervical glandular hyperplasia (LEGH), has been identified and has been predicted to be a precancerous lesion of MDA. The first case of LEGH induced by a germline STK11 mutation has also been described. A high risk of endometrial cancer in PJS has also been reported. These developments suggest that PJS is an important syndrome of hereditary gynecological tumors that requires further study.

Usefulness of a management protocol for patients with cervical multicystic lesions: A retrospective analysis of 94 cases and the significance of GNAS mutation

“…Ohta et al reported a case with sequential lesion of LEGH, LEGH with atypia, and MDA,30 supporting this concept. In addition, the tumor suppressor STK11 gene mutation has been of interest since the patients of Peutz‐Jeghers syndrome harboring its mutation have been reported to associate with LEGH, MDA, and adenocarcinoma 31. Kuragaki et al reported that 55% of MDA cases had a mutation in the STK11 gene 32.…”

“…In addition, the tumor suppressor STK11 gene mutation has been of interest since the patients of Peutz-Jeghers syndrome harboring its mutation have been reported to associate with LEGH, MDA, and adenocarcinoma. 31 Kuragaki et al reported that 55% of MDA cases had a mutation in the STK11 gene. 32 We also reported that STK11 may be involved in the progression of LEGH to MDA, according to a case containing mixed lesion of LEGH and MDA with the same clonality, whereas STK11 gene mutation was observed only in MDA lesion.…”

Specific deletion of LKB1/ Stk11 in the Müllerian duct mesenchyme drives hyperplasia of the periurethral stroma and tumorigenesis in male mice

“…In patients with PJS, the incidence of adenoma malignum of the uterine cervix (MDA), a usually rare form of cervical cancer, is estimated at between 15% and 30%, and patients with PJS account for 10% of the total cases (49). In another study of 11 MDA tumors from patients without PJS, six had mutations in STK11 with loss of heterozygosity.…”

Gastric‐type endocervical glandular neoplasms associated with aberrant p16 expression and K‐RAS gene mutation in Peutz‐Jeghers syndrome

“…In gynecology, there has been a particular focus on sex cord tumor with annular tubules and minimal deviation adenocarcinoma (MDA). The incidence of MDA in PJS patients is estimated to be 15–30%, while up to 10% of MDA cases complicate with PJS . Kuragaki and colleagues identified six somatic STK11 mutations out of 11 MDA (55%), and suggested that the onset of MDA may be associated with the defective expression and/or post‐translational modification of the STK11 protein .…”

“…The incidence of MDA in PJS patients is estimated to be 15-30%, while up to 10% of MDA cases complicate with PJS. 3,4 Kuragaki and colleagues identified six somatic STK11 mutations out of 11 MDA (55%), and suggested that the onset of MDA may be associated with the defective expression and/or post-translational modification of the STK11 protein. 5 In contrast, the coexistence of lobular endocervical glandular hyperplasia (LEGH) with MDA has led to the hypothesis that LEGH was a premalignant lesion of MDA.…”