Role of estrogen receptor alpha in human cervical cancer-associated fibroblasts: a transcriptomic study.

Cancer-Associated Fibroblasts (CAFs) are crucial in genesis and progression of tumors; however, cervical CAFs (C-CAFs) are not well characterized. Estradiol (E2) has been implicated as a cofactor in human papillomavirus (HPV)-mediated cervical cancer (CxCa), both in animal models and in women using oral contraceptives; however, the exact role of the hormone is unclear. Human C-CAFs have recently been shown to express estrogen receptor alpha (ER-α). We investigated gene expression patterns in ex vivo cultured early and late stage C-CAFs in the context of E2. CAFs were isolated from four patients with early and two patients with late stage CxCa. ER-α expression in CxCa tissues was localized to stromal fibroblast-like cells and confirmed in ex vivo cultured C-CAFs. Two ER antagonists (ICI 182,780 and Methyl Piperidino Pyrazole) were used to unravel ER signaling in CAFs. Microarray technology was used for expression profiling and validated by quantitative reverse transcription PCR. The transcriptomes of C-CAFs across stages indicated their activated state. C-CAFs had gene expression patterns associated with both pro-tumorigenic and pro-inflammatory signaling. Late-stage C-CAFs compared to those of early stage appeared to be more actively metabolizing and cycling but expressed fewer genes related to immune function. We report differential expression profiles between C-CAFs: early vs. late stage and in the presence of ER antagonists. Both ER antagonists seemed to modulate C-CAF function by down regulating genes associated with cell cycle and metabolism, affecting angiogenesis and cancer progression. This study characterized C-CAFs from early and late stage disease, and experiments with ER inhibitors emphasized the probable importance of canonical ER-α signaling. Interfering with paracrine signaling through fibroblast ER-α is worth exploiting as a targeted therapy in CxCa management.

Colposcopy in oral epithelial dysplasia: seeing the unseen, a pilot study.

CONTEXT: The diagnosis of malignant and potentially malignant epithelial lesions of oral mucosa cannot be based solely on clinical findings. The histologic evaluation of a representative biopsy specimen thus becomes necessary. The site for biopsy, however, is always a subjective choice that sometimes raises doubts about its representativeness. So far, no simple and reliable method is available for the selection of the most appropriate area for biopsy. Colposcopy is helpful in the selection of these sites of epithelial dysplasia depending upon the vascular patterns. AIMS: The study was planned to assess the role of colposcopic examination in the selection of biopsy site in patients with varying grades of oral epithelial dysplasia at various sites. SETTINGS AND DESIGN: Fifty patients between the ages of 30-60 years clinically diagnosed with leukoplakia and carcinoma buccal mucosa were included in the study. MATERIALS AND METHODS: For each of the subject, a thorough clinical examination followed by colposcopic assessment was carried out for the selection of biopsy site from the involved mucosa. The histopathological findings were then compared in the two cases and results analyzed. STATISTICAL ANALYSIS USED: The statistical analysis was done using paired t-test. RESULTS: In our study, sensitivity and specificity for the selection of biopsy site by colposcopic examination came out to be higher for leukoplakia than carcinoma buccal mucosa patients. CONCLUSIONS: It was concluded that colposcopic examination was found more significant in the selection of biopsy site for leukoplakia patients while clinical criterion was found to be more appropriate for carcinoma buccal mucosa cases.