Avaliação das alterações dermatológicas e estudo imunohistoquímico do receptor estrogênico α e da proteína Menin em lesões cutâneas de portadores de neoplasia endócrina múltipla tipo 1

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited syndrome characterized by the mutation in MEN 1, the gene which encodes menin protein. Recent studies have revealed the importance of other clinical features related to NEM1, including the presence of cutaneous lesions, some of which being more related to angiofibromas, lipomas and collagenomas. Complete loss of MEN 1 GEN occurs in these lesions; however, it is not known if there is alteration in the expression of menin. Menin acts on tumorigenesis in cell type dependence, its action as estrogen receptor α (REα) was described in mammary tissue promoting cell proliferation by reducing apoptosis. The coactivation of REα by menin in the mammary tissue increases expression of this estrogen receptor. In NEM1 patients with breast tumor, this receptor is less expressed, and tumorigenesis is induced by another pathway. Objective: To identify the prevalence of cutaneous lesions in patients with MEN-1 and their association with the main tumors. To analyze and to compare the immunolabeling of menin protein and REα in the found lesions and in normal skin. Method: Dermatological examination, questionnaire filling and cutaneous biopsy were carried out in selected cases in patients with clinical diagnosis of MEN1 and in their asymptomatic first-degree as well as immunohistochemistry (IHC) for the expression of the menin protein and REα in 11 lesions (collagenomas and angiofibromas) and in 16 normal skin samples from healthy individuals. Results: Evaluation of 53 patients with NEM-1, age 40.3 ± 12SD (16min-69max years), 35 (66%) women. Among them, 31 (58%) had collagenomas, 6 (11%) angiofibromas and 5 (9%) lipomas. In the 14 asymptomatic relatives, 12 (86%) were women aged 22.5 ±11 SD (11min-48max years). Only 2 (14%) had collagenomas. No association between the presence of cutaneous lesions and the presence of HT, hyperparathyroidism and TGEP (p = 0.100) was found IHC revealed reduction in the immunopositivity of menin (p <0.001) and REα (p = 0.038) in collagenomas and angiofibroma compared to normal skin, but with no correlation between the expression of menin and REα in both groups (p = 0.6 and p = 0.8 respectively). Conclusion: In our environment, presence of collagenomas in the trunk region in young individuals is an alert to the possibility of NEM-1. Reduction in menin expression may be implicated in the development of these cutaneous lesions. However, in the type of lesion analyzed, it was not possible to establish a relationship between the expression of menin and of alpha receptor, which seems to occur by mechanisms different from those already reported in mammary tissue.