Parathyroid Hormone-related Peptide (PTH-rp) in Normal, Hyperplastic and Malignant Endometrial Tissue: an Immunohistochemical Analysis

Abstract

Parathyroid hormone-related peptide (PTH-rp) is a peptide initially purified from tumors with hypercalcemia, which is also produced in human endometrium. The aim of this study was to determine the frequency and tissue distribution of PTH-rp in normal, hyperplastic and malignant endometrium. Materials and Methods: Paraffin-fixed endometrial tissue was obtained randomly from women in the proliferative (n=4), early secretory (n=5) and late secretory (n=5) phases, as well as glandular-cystic hyperplasia (n=5), adenomatous hyperplasia (AH) grade I (n=5), grade II (n=4), grade III (n=4) and endometrioid adenocarcinoma grade I (n=5). The PTH-rp expression was evaluated by immunohistochemical procedure. A semiquantitative analysis and a statistical evaluation was performed. Results: Immunohistochemical reaction with PTH-rp was primarily observed in glandular and luminal epithelial cells. Stromal and myometrial cells also expressed PTH-rp. The expression of PTH-rp in glands was significantly higher during the late secretory than in the proliferative phase. The highest expression was observed during AH grade III, while the lowest reaction was detected in the proliferative phase and adenocarcinoma. Discussion: PTH-rp was expressed in normal, hyperplastic and malignant endometrial tissue. A cyclical expression of PTH-rp in normal glandular epithelium was observed, being more prominent in the late secretory phase. AH grade I to III also expressed PTH-rp with higher immunostaining than adenocarcinoma. Since AH grade III can be considered as a precursor of endometrial cancer, PTH-rp could be a marker of cell transformation. Endometrioid adenocarcinoma expressed the lowest PTH-rp immunostaining, indicating either a lower expression or a reflection of an increased PTH-rp shedding of malignant transformed endometrium. Further studies are required to establish the usefuleness of PTM-rp as a marker in different endometrial pathologies.