Epithelial membrane protein-2 expression is an early predictor of endometrial cancer development.

BACKGROUND: Endometrial cancer (EC) is a common malignancy worldwide. It is often preceded by endometrial hyperplasia, whose management and risk of neoplastic progression vary. Previously, the authors have shown that the tetraspan protein epithelial membrane protein-2 (EMP2) is a prognostic indicator for EC aggressiveness and survival. Here the authors validate the expression of EMP2 in EC, and further examine whether EMP2 expression within preneoplastic lesions is an early prognostic biomarker for EC development. METHODS: A tissue microarray (TMA) was constructed with a wide representation of benign and malignant endometrial samples. The TMA contains a metachronous cohort of cases from individuals who either developed or did not develop EC. Intensity and frequency of EMP2 expression were assessed using immunohistochemistry. RESULTS: There was a stepwise, statistically significant increase in the average EMP2 expression from benign to hyperplasia to atypia to EC. Furthermore, detailed analysis of EMP2 expression in potentially premalignant cases demonstrated that EMP2 positivity was a strong predictor for EC development. CONCLUSIONS: EMP2 is an early predictor of EC development in preneoplastic lesions. In addition, combined with our previous findings, these results validate EMP2 as a novel biomarker for EC development.

Availability and quality of paraffin blocks identified in pathology archives: a multi-institutional study by the Shared Pathology Informatics Network (SPIN).

BACKGROUND: Shared Pathology Informatics Network (SPIN) is a tissue resource initiative that utilizes clinical reports of the vast amount of paraffin-embedded tissues routinely stored by medical centers. SPIN has an informatics component (sending tissue-related queries to multiple institutions via the internet) and a service component (providing histopathologically annotated tissue specimens for medical research). This paper examines if tissue blocks, identified by localized computer searches at participating institutions, can be retrieved in adequate quantity and quality to support medical researchers. METHODS: Four centers evaluated pathology reports (1990-2005) for common and rare tumors to determine the percentage of cases where suitable tissue blocks with tumor were available. Each site generated a list of 100 common tumor cases (25 cases each of breast adenocarcinoma, colonic adenocarcinoma, lung squamous carcinoma, and prostate adenocarcinoma) and 100 rare tumor cases (25 cases each of adrenal cortical carcinoma, gastro-intestinal stromal tumor [GIST], adenoid cystic carcinoma, and mycosis fungoides) using a combination of Tumor Registry, laboratory information system (LIS) and/or SPIN-related tools. Pathologists identified the slides/blocks with tumor and noted first 3 slides with largest tumor and availability of the corresponding block. RESULTS: Common tumors cases (n = 400), the institutional retrieval rates (all blocks) were 83% (A), 95% (B), 80% (C), and 98% (D). Retrieval rate (tumor blocks) from all centers for common tumors was 73% with mean largest tumor size of 1.49 cm; retrieval (tumor blocks) was highest-lung (84%) and lowest-prostate (54%). Rare tumors cases (n = 400), each institution's retrieval rates (all blocks) were 78% (A), 73% (B), 67% (C), and 84% (D). Retrieval rate (tumor blocks) from all centers for rare tumors was 66% with mean largest tumor size of 1.56 cm; retrieval (tumor blocks) was highest for GIST (72%) and lowest for adenoid cystic carcinoma (58%). CONCLUSION: Assessment shows availability and quality of archival tissue blocks that are retrievable and associated electronic data that can be of value for researchers. This study serves to compliment the data from which uniform use of the SPIN query tools by all four centers will be measured to assure and highlight the usefulness of archival material for obtaining tumor tissues for research.

Aberrant HOXC expression accompanies the malignant phenotype in human prostate.

Dysregulation of HOX gene expression has been implicated as a factor in malignancies for a number of years. However, no consensus has emerged regarding specific causative genes. Using a degenerate reverse transcription-PCR technique, we show up-regulation of genes from the HOXC cluster in malignant prostate cell lines and lymph node metastases. When relative expression levels of the four HOX clusters were examined, lymph node metastases and cell lines derived from lymph node metastases exhibited very similar patterns, patterns distinct from those in benign cells or malignant cell lines derived from other tumor sites. Specific reverse transcription-PCR for HOXC4, HOXC5, HOXC6, and HOXC8 confirmed overexpression of these genes in malignant cell lines and lymph node metastases. Laser capture microdissection and examination of paired tumor/normal prostate epithelial cells also indicated overexpression of these HOXC genes in primary tumor cells. Our data indicate a possible link between expression of HOXC genes and malignancy in prostate cells. Overexpression of HOXC8 in LNCaP prostate cancer cells suppressed transactivation by androgen receptors. We speculate that HOXC overexpression may predispose tumor cells to androgen independence by necessitating adaptation to diminished androgen signaling.