Cyclin D1, cyclin E, and p21 have no apparent prognostic value in anal carcinomas treated by radiotherapy with or without chemotherapy

Abstract

The purpose of this study was to assess the potential prognostic and/or predictive value of the expression of cyclin D1, cyclin E, and p21 protein in a series of 98 anal carcinomas (T1 -4, N0 -3) treated by radiotherapy with (51) or without (47) chemotherapy in one institution. Correlation with Mib1 index and p53 expression was also investigated. Median follow-up for surviving patients was 124 months (range: 30 -266). Immunohistochemical staining was performed on pretreatment biopsies, applying a standard ABC technique for cyclin D1 (clone DSC6, DAKO, 1 : 300), cyclin E (clone 13A3, Novocastra, 1 : 100), p21 WAF/CIP1 (clone SX118, DAKO, 1 : 50), p53 (clone DO7, DAKO, 1 : 200), and Mib1 (Ki-67, Dianova, 1 : 20). Tumours were classified into low-or high-expression groups according to the expression level of the protein considered. High expression was found in 51% of tumours for cyclin E, in 33.7% for cyclin D1, and in 65% for p21. None of those factors were significantly associated with clinical variables such as advanced T or N categories. In a monovariate analysis, advanced T and N categories and longer overall treatment time were the only variables that correlated significantly with low rate of local control (LC) and disease-free survival. However, in a subgroup analysis, high p21 expression correlated with a trend for significantly higher 5-year LC (87 vs 68%, P ¼ 0.07) in the N0 patients. The results of this study suggest that the cell-cycle proteins investigated are unlikely to be clinically useful in predicting treatment response or prognosis in patients with anal carcinomas.

Prognostic significance of Cyclin A in epidermoid anal cancer

“…In another study on a patient series of similar size these results could not be confirmed (13). The results on p21 of our study are in accord with those of Allal et al (13) and fail to show the prognostic impact of p21 in anal epidermoid cancer.…”

“…A few reports on the proliferation markers other than Cyclin A, in epidermoid anal cancer, have been published (13,(16)(17)(18). A high proliferation index, measured with Ki-67, was significantly associated with better colostomy-free survival in 29 patients reported by Grabenbauer et al (16).…”

“…- ----------------------------------------------------------------------------------------------------value of Cyclin D1 or Cyclin E, both reflecting proliferation rates (13).…”

HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination

“…The cases were interpreted as positive for p21 if more than 5% of the tumors cells showed nuclear staining [13] and were considered positive to ER, PR and p53 protein expression if more than 10% of the tumors cells showed nuclear staining. HER-2 expression was scored according to the degree and the proportion of membrane staining according to HercepTest protocol [14,15].…”

Immunohistochemical Analysis of Cell Cycle-Related Molecules in Gastric Carcinoma: Prognostic Significance, Correlation with Clinicopathological Parameters, Proliferation and Apoptosis

“…Cyclin D1 overexpression was associated with low-grade tumors of breast carcinomas [6] . The overexpression of cyclin E had no prognostic value in anal cancer [7] , cervical cancer [8] and gastrointestinal stromal tumor [9] . The expression of p27 positively correlated with poor prognosis in esophageal squamous carcinoma [10] .…”