Cyclin D1 and retinoblastoma protein in vulvar cancer and adjacent lesions

Abstract

Abnormalities in the cell cycle are associated with tumorigenesis but have not yet been identified in squamous cell carcinoma (SCC) of the vulva or in adjacent vulvar lesions. The purpose of this study was to identify cell cycle protein expression (cyclin D1 and retinoblastoma protein [pRb]) in vulvar SCC and in adjacent potentially premalignant lesions: lichen sclerosis (LS), squamous cell hyperplasia (SH), and vulvar intraepithelial neoplasia (VIN). Using immunohistochemical techniques, 57 SCCs were analyzed with 19 adjacent areas showing LS, 13 showing SH, 11 VIN, and six normal epithelium. Fifty-one percent of SCCs showed abnormal cyclin D1 expression and 37% showed abnormal pRb. Abnormal cyclin D1 expression in the adjacent areas was as follows: 53% in LS, 31% in SH, 18% in VIN, and 0% in normal. Abnormal pRb expression was as follows: 42% in LS, 62% in SH, 46% in VIN, and 33% in normal. Only 10 lesions showed abnormal expression of both proteins. Abnormal expression of cyclin D1 in SCC was statistically significant compared with adjacent normal epithelium. In SCC lesions, abnormal cyclin D1 expression was associated with greater depth of invasion. Abnormal pRb in SCC was associated with poor tumor grade. Cyclin D1 and pRb are separately involved in the progression of vulvar cancer, and changes in the expression of these proteins may represent an early stage of malignant transformation in vulvar disease.

Metastasizing vulvar carcinosarcoma with squamous carcinomatous and leiomyosarcomatous differentiation: genetic evidence of clonal origin

“…The cyclin D1 gene maps to this amplicon [9]. Cyclin D1 is an important cell cycle-control gene that has been shown to be abnormally expressed in half of all cases of vulvar squamous cell cancer [10]. In keeping with this, we immunohistochemically found a strong nuclear reactivity for cyclin D1 in the carcinomatous tumor component and a weaker, albeit specific, staining in the sarcomatous component.…”

RB family members as predictive and prognostic factors in human cancer

“…The loss of pRb increased from stage I carcinoma (16.7%) through stage II (26.7%) and III (44.4%), to IV (50%), and was correlated with poor tumor grade (Rolfe et al, 2001), suggesting that pRb may play an important role in tumor progression. As to pRb2 expression, its decrease from vulvar benign lesions, to VIN and to invasive squamous cell carcinoma, suggests a role in vulvar carcinogenesis, although pRb2 status does not correlate with any clinicopathological parameter (Zamparelli et al, 2001).…”

HPV related VIN: Highly proliferative and diminished responsiveness to extracellular signals

“…Although p16 upregulation is a very sensitive marker for VIN, it does not result in downregulation of the cell cycle because downregulation of its downstream effectors cyclinD1 and cyclinD2 is successfully neutralized by upregulation of cyclinE1, cyclinE2, cyclinA2, cyclinB1 and cyclinB2. Interestingly, cyclinD1 is upregulated in many cancers, including vulvar cancer, 24 which could indicate that cyclinD1 can play a role in progression of VIN to an invasive tumor.…”