LH/hCG-Receptor Expression May Have a Negative Prognostic Value in Low-Risk Endometrial Cancer

Introduction: A 51 years-old woman was diagnosed with endometrial cancer and underwent surgical staging. Pathologic evaluation showed a 2x1 cm G2 endometrioid endometrial cancer with a 30% myometrial deep invasion (FIGO stage 1A). The patient was classified as low-risk of recurrence and no adjuvant treatment was offered. Six months after surgery, the patient developed an early vescico-vaginal recurrence and chemotherapy treatment was started. Few months later a subsequent involvement of vaginal wall, ileum and omentum was detected and the patient underwent second surgery. Background: LH/hCG-receptor (LH/hCG-R) expression has been previously reported to be associated with an invasive phenotype in endometrial cancer cells. Moreover, in a preclinical mouse model of EC behaves as a pro metastatic molecular device. Discussion: We analysed the expression level of LH/hCG-R in cancer specimens collected during surgeries. Molecular and immunohistochemical analysis showed a strong expression of both mRNA and protein for LH/hCG-R in all specimens. Conclusion: LH/hCG-R expression may be assessed together with other clinicopathological parameters in order to better predict the risk of recurrence in low-risk endometrial cancer patients. Further clinical trials are warranted in order to validate LH/hCG-R as biomarker in endometrial cancer

Over-Expression of the LH Receptor Increases Distant Metastases in an Endometrial Cancer Mouse Model

Objective: The aim of the present study was to define the role of luteinizing hormone receptor (LH-R) expression in endometrial cancer (EC), using preclinical mouse models, to further transfer these data to the clinical setting. Materials and Methods: The role of LH-R over-expression was studied using EC cells (Hec1A, e.g., cells with low endogenous LH-R expression) transfected with the LH-R (Hec1A-LH-R). In vitro cell proliferation was measured through the WST-1 assay, whereas cell invasion was measured trough the matrigel assay. The effects of LH-R over-expression in vivo were analyzed in an appropriately developed preclinical mouse model of EC, which mimicked postmenopausal conditions. The model consisted in an orthotopic xenograft of Hec1A cells into immunodeficient mice treated daily with recombinant LH, to assure high levels of LH. Results: In vitro data indicated that LH-R over-expression increased Hec1A invasiveness. In vivo results showed that tumors arising from Hec1A-LH-R cells injection displayed a higher local invasion and a higher number of distant metastases, mainly in the lung, compared to tumors obtained from the injection of Hec1A cells. LH withdrawal strongly inhibited local and distant metastatic spread of tumors, especially those arising from Hec1A-LH-R cells. Conclusion: The over-expression of the LH-R increases the ability of EC cells to undergo local invasion and metastatic spread. This occurs in the presence of high LH serum concentrations