Clonality analysis suggests that STK11 gene mutations are involved in progression of lobular endocervical glandular hyperplasia (LEGH) to minimal deviation adenocarcinoma (MDA)

Abstract

Lobular endocervical glandular hyperplasia (LEGH) is a benign proliferative disease of cervical glands. Although histological resemblance of minimal deviation adenocarcinoma (MDA) to LEGH and frequent association of LEGH with MDA have been reported, it still remains unclear whether LEGH is a precancerous lesion of MDA. The present study was undertaken to examine the pathogenetic relationship between LEGH and MDA using a clonality analysis and mutational analyses of the STK11 gene, of which mutations have been reported in MDA. Of nine cases of LEGH only, four were polyclonal and five were monoclonal in composition. Of six LEGH lesions associated with MDA or adenocarcinoma, two were polyclonal and four were monoclonal. In cases of MDA or adenocarcinoma coexisting with LEGH, the patterns of X chromosome inactivation in malignant lesions were identical to those in coexisting LEGH lesions. A mutation of STK11 was only identified in one MDA, but not in LEGH. These results indicate that a subset of LEGH may be a precursor to malignant tumors including MDA and that a mutation of STK11 may be involved in progression of LEGH to MDA.

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

“…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 12. In the present study, GNAS gene mutations were detected in two (14.3%) out of 14 cases of LEGH.…”

“…Although LEGH was first reported as a benign disease, it has been reported as a precursor of MDA, because of frequent association between LEGH and MDA as well as its genetic characteristics 6, 7, 8, 9, 10, 11. We previously reported that some LEGH lesions were a precancerous form of MDA due to the pattern of X chromosome inactivation using the human androgen receptor (HUMARA) method 12. Therefore, the possibility of a focal association with carcinoma in LEGH needs to be considered in its management.…”

Endocervical gastric-type adenocarcinoma, an unrelated HPV tumour: difficulties in screening and diagnosis

“…Recent findings have identified gene mutations that suggest MDA is an evolutionary lesion due to LEGH progression 15. Gastric-type adenocarcinomas are present in the upper endocervix as a bulky cervix, are typically p16 negative, demonstrate gastric differentiation in immunohistochemical reactions, and may be associated with LEGH, the putative precursor 5 11…”

Successful pregnancy in a Peutz–Jeghers syndrome patient with lobular endocervical glandular hyperplasia

“…As it is known that MDA complicates PJS, and LEGH has been suggested to be a precursor of MDA and adenocarcinoma, hysterectomy was also considered for our patient. Lesions of LEGH and MDA tend to be present near the internal os, rather than the squamocolumnar junction .…”