Changes in the expression of oestrogen receptors and E-cadherin as molecular markers of progression from normal epithelium to invasive cancer in elderly patients with vulvar squamous cell carcinoma.

Aims: The most common vulvar squamous cell carcinoma (conventional SCC) occurs in elderly women and develops following a human papillomavirus (HPV)-negative pathway. Because the highest incidence of conventional SCC is observed in patients with low oestrogen levels (postmenopausal women), the aim was to investigate whether hormonal factors could play a role in the development of cancer. Methods and results: The expression profile of oestrogen receptor alpha (ER alpha), ER beta and progesterone receptor (PR) in a section containing both normal and tumour tissue, as well as the SCC-associated vulvar lesion, was evaluated in 34 elderly patients. Also, as recent studies have identified E-cadherin as a novel transcriptional target of oestrogen signalling, the modulation of this epithelial-mesenchymal transition (EMT) marker was studied. Finally, the expression of the proliferation marker Ki67 and of the apoptotic marker p53 was assessed. Results showed that changes in both ER alpha and ER beta expression characterize the transition from normal epithelium to cancer in patients with vulvar SCC: ER alpha was lost in cancer while ER beta decreased, mainly showing cytoplasmic localization. A reduction in the expression of E-cadherin was also observed in tumours, compared to normal epithelium. Conclusions: The data put the ER signalling pathway into the spotlight as a potentially important factor in vulvar carcinogenesis.