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Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various tumors, including endometrial carcinomas (EC). However, tumoral receptors that mediate the antiproliferative effects of GHRH antagonists in human ECs have not been fully characterized. In this study, we investigated the expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors (GHRH-R) in 39 human ECs and in 7 normal endometrial tissue samples using RT-PCR. Primers designed for the PCR amplification of mRNA for the full length GHRH-R and SVs were utilized. The PCR products were sequenced, and their specificity was confirmed. Nine ECs cancers (23%) expressed mRNA for SV1, three (7.7%) showed SV2 and eight (20.5%) revealed mRNA for SV4. The presence of SVs for GHRH-Rs could not be detected in any of the normal endometrial tissue specimens. The presence of specific, high affinity GHRH-Rs was also demonstrated in EC specimens using radioligand binding studies. Twenty-four of the investigated thirty-nine tumor samples (61.5%) and three of the seven corresponding normal endometrial tissues (42.9%) expressed mRNA for GHRH ligand. Our findings suggest the possible existence of an autocrine loop in EC based on GHRH and its tumoral SV receptors. The antiproliferative effects of GHRH antagonists on EC are likely to be exerted in part by the local SVs and GHRH system. [ABSTRACT FROM AUTHOR]

Introduction Peritoneal dissemination accompanied by ascites formation is common in epithelial ovarian cancer (EOC). Adhesion molecules are crucial in metastatic spread and the latter involves epithelial-mesenchymal transition (EMT). This study aimed at: (1) clarifying whether E-cadherin and β-catenin expression and proliferative activity in metastatic ovarian cancer are inter-related; (2) Identifying possible correlations between cell adhesion molecular expression profiles, the proliferative activity and p53 expression of tumor cells and tumor grade and stage; (3) testing the cytology microarray (CMA) technique in analyzing metastasis formation. Material and methods Both tumorous and ascitic samples from 27 EOC patients were examined by using tissue microarray (TMA) and cytology microarray (CMA), respectively. CMA blocks were constructed using cores from each cell block of the ascitic specimens. Expression of E-cadherin, β-catenin, Ki-67 and p53 was immunohistochemically detected both in TMA and CMA blocks. Results E-cadherin expression was higher in ascitic cells than in primary tumor cells (p = .294). β-catenin expression was significantly lower in ascitic cells than in primary tumor cells (p = .006). Expression of Ki-67 was lower and expression of p53 was higher in primary tumors than in ascitic cells, for p53 the difference was significant (p = .001). Both Ki-67 and p53 expression elevated significantly in high-grade primary tumor cells and in ascites cells (p = .039, and p = .004, respectively). Conclusion Epithelial-mesenchymal transition- mesenchymal-epithelial transition is suggested as the best descriptive term for our IHC observations which accompany increased proliferative activity of ascitic cells. The CMA method is an adequate and reliable method for the analysis of ascitic tumor cells disseminating from ovarian malignancies. [ABSTRACT FROM AUTHOR]