Expression of maspin in endometrioid adenocarcinoma of endometrium.

Maspin is a member of the serpin family, whose expression is altered in neoplasia and malignancies of many tissues. Underexpression of maspin has been reported in breast and prostatic cancers, but in some cancers such as ovarian, colorectal and pancreatic carcinoma, it was found to be up-regulated. This study aimed at demonstrating the expression of maspin in human endometrial tissue and searching for any altered expression in endometrioid adenocarcinoma of the endometrium compared to normal endometrium. The expression level of the maspin gene was studied using reverse transcriptase-polymerase chain reaction (RT-PCR) performed on RNA extracted from 34 endometrial cancer samples (including 24 with FIGO stage I disease and 10 with FIGO stage III disease) and 28 normal endometrium in proliferative or secretory phases. Immunohistochemical staining was also performed on 10 cases of endometrial cancer (6 FIGO stage I cases and 4 FIGO stage III cases) as well as 15 normal endometrium. Semi-quantitative RT-PCR revealed that the expression of maspin was significantly up-regulated in both stage I (p<0.01) and stage III (p<0.01) endometrial cancer compared with normal endometrium. However, no significant difference in maspin expression was demonstrated between stage I and stage III endometrial cancer. Immunostaining of all tissue sections revealed an immunopositive signal in the nuclei of the normal or cancerous endometrial glandular cells. In 60% of the cancer cases, cytoplasmic staining was also evident. Our results suggested that there is up-regulated expression of maspin in endometrioid endometrial adenocarcinoma. Cytoplasmic immuno-expression of maspin is common in endometrial cancer. It may play a role in the malignant transformation of human endometrial tissue.

Epigenetic and genetic alternation of PTEN in cervical neoplasm.

OBJECTIVES: We studied the role of epigenetic and genetic changes of PTEN in the development of squamous cell carcinoma (SCC) of the uterine cervix and their value as a prognostic factor. METHODS: Ten high-grade cervical intraepithelial neoplasia (CIN-H) and 62 SCC tissues were used in this study. Microdissection was performed before loss of PTEN function through methylation of promoter CpG islands, deletion and mutation were studied. The findings were verified with PTEN protein expression and correlated with clinicopathologic information. RESULTS: PTEN mutation assessed by single-strand conformation polymorphism (PCR-SSCP) was not noted in any of the 62 SCC. Loss of heterozygosity (LOH) was only seen in eight SCC. PTEN promoter methylation was detected in 40% (4/10) of CIN-H and 58% (36/62) of SCC specimens. Loss of PTEN protein expression was associated with methylation of PTEN. PTEN methylation was not related to patient age, tumor grade or stage. Patients with persistent disease or who died of disease had a significantly higher percentage of PTEN methylation than those without evidence of recurrence. Multivariate Cox regression models confirmed PTEN was an important significant predictor both for total and disease-free survival after controlling age, pathologic grade and clinical stage. CONCLUSIONS: PTEN methylation and loss of PTEN expression are early events in the development of cervical cancer and may have prognostic significance.

Expression genomics of cervical cancer: molecular classification and prediction of radiotherapy response by DNA microarray.

PURPOSE: The incidence and mortality rates of cervical cancer are declining in the United States; however, worldwide, cervical cancer is still one of the leading causes of death in women, second only to breast cancer. This disparity is at least partially explained by the absence of or comparatively ineffective screening programs in the developing world. Recent advances in expression genomics have enabled the use of DNA microarray to profile gene expression of various cancers. These expression profiles may be suitable for molecular classification and prediction of disease outcome and treatment response. We envision that expression genomics applied in cervical cancer may provide a more rational approach to the classification and treatment of the disease. EXPERIMENTAL DESIGN: In this report, we examined the expression profiles of cervical cancer compared with normal cervical tissues in DNA microarrays that contained approximately 11,000 features that correspond to either human transcripts with known function or anonymous expressed sequence tags. RESULTS: Our results showed that normal cervical tissues were completely segregated from the cancer samples using about 40 genes whose expressions were significantly different between these specimens. In addition, clinical stage IB and stage IIB tumors could also be classified based on their signature expression patterns. Most importantly, some of the tumor samples were further stratified into two major groups based on their response to radiotherapy, and we were able to predict the response of these patients to radiotherapy from their expression profiles. CONCLUSIONS: Gene expression profiling by DNA microarray may be used for further molecular classification of disease stages and prediction of treatment response in cervical cancer.