Аннотация:Introduction: Patients with two or more tumors associated with multiple endocrine neoplasia type 1 (MEN1) harboring no MEN1 mutations are designated as MEN1 phenocopies (phMEN1); most of them have a combination of pituitary adenomas and primary hyperparathyroidism (PHPT).Aim: To evaluate menin expression in parathyroid tumors of patients with phMEN1 in comparison with parathyroid tumors of genetically confirmed MEN1 (gMEN1) and sporadic PHPT (sPHPT).Materials and methods: Immunohistochemical staining for menin (Abcam, ab2605, UK) was performed on FFPE parathyroid tumor samples from eight patients with phMEN1 (6 – PHPT + acromegaly, 1 – PHPT + Cushing’s disease, 1 – PHPT + prolactinoma), nine patients with gMEN1 and 10 patients with sPHPT. Menin expression was evaluated as either nuclear or cytoplasmic or both (positive or negative, positive expression was scored as absent, weak, intermediate or strong).Results: phMEN1 group included 2 males, 6 females (2 atypical parathyroid adenomas in males and parathyroid adenomas in all females). gMEN1 group included 2 males, 7 females (8 – parathyroid adenomas, 1 - hyperplasia). sPHPT included 2 males, 8 females, all had parathyroid adenomas. Groups did not differ in sex, calcium and parathyroid hormone levels. phMEN1 patients were older than gMEN1 (p=0,000056). Nuclear menin expression was positive in 6 phMEN1 (2 – weak, 3 – intermediate, 1 - strong), 0 gMEN1, 6 sPHPT (2 – intermediate, 4 - strong). Cytoplasmic menin expression was positive in 4 phMEN1 (1 – weak, 3 - intermediate), 1 gMEN1 (weak), 7 sPHPT (4 – weak, 3 - intermediate). phMEN1 and gMEN1 groups, and sPHPT and gMEN1 groups differed in nuclear menin expression (р=0,0085 and р=0,0050 respectively). gMEN1 and sPHPT groups differed in cytoplasmic menin expression (р=0,0094). phMEN1 and gMEN1 groups, and sPHPT and gMEN1 groups differed in nuclear and/or cytoplasmic menin expression (р=0,045 and р=0,0094 respectively). Despite no statistically significant difference of menin expression between phMEN1 and sPHPT groups, it was noteworthy that menin expression was stronger in sPHPT and was weaker in phMEN1.Conclusion: Menin expression is preserved in parathyroid tumors of phMEN1 in comparison with gMEN1, though it seems to be attenuated compared to sporadic parathyroid tumors. This may indicate that different mechanisms are involved in parathyroid tumorigenesis in phMEN1.
