ORIGINAL ARTICLE

Expression of the cell cycle regulatory proteins p34^cdc2, p21^waf1, and p53 in node negative invasive ductal breast carcinoma

H P Kourea¹, A K Koutras², C D Scopa¹, M N Marangos², E Tzoracoeleftherakis³, D Koukouras³, H P Kalofonos²

¹ Department of Pathology, University Hospital of Patras, Patras Medical School, Patras, Rion 26500, Greece
² Department of Internal Medicine, University Hospital of Patras
³ Department of Surgery, University Hospital of Patras

Correspondence to:
Correspondence to:
Dr H P Kourea
Department of Pathology, "Agios Andreas" Peripheral General Hospital of Patras, Patras, 26335 Greece; hkourea{at}yahoo.com

Aims: To look for correlations between expression of cell cycle regulatory proteins p34^cdc2, p21^WAF1, and p53 in node negative invasive ductal breast carcinoma, or between these proteins and clinicopathological parameters, and to assess their prognostic value.

Methods: Immunohistochemistry using formalin fixed, paraffin wax embedded sections from 94 breast carcinomas. Adjacent benign epithelial breast tissue was available in 74 cases. Median follow up was 72 months.

Results: Nuclear and cytoplasmic p34^cdc2 expression was seen in 80 and 62 tumours, respectively; nuclear expression was seen in adjacent benign epithelium in 12 cases. p21^WAF1 and p53 were positive in 48 and 21 tumours, respectively. High expression of p34^cdc2 in neoplastic nuclei was associated with higher histological grade and p53 expression, but not with tumour size, steroid receptor status, patient age, menopausal status, recurrence, metastasis, disease free survival (DFS), or overall survival (OS). p34^cdc2 in tumour cytoplasm was associated with p34^cdc2 nuclear positivity, high tumour grade, and DFS in univariate but not multivariate analysis. In contrast, p34^cdc2 expression in benign tissue independently predicted DFS and OS in univariate and multivariate analysis. Expression of p53 was associated with high tumour grade and negative steroid receptors, but not with recurrence, metastasis, DFS, or OS. p21^WAF1 expression was not associated with the examined parameters.

Conclusions: p34^cdc2, p21^WAF1, and p53 expression does not predict outcome in node negative breast carcinoma, although p34^cdc2 expression in benign tissue is related to prognosis. The association between p34^cdc2 and p53 implicates p53 in G2–M cell cycle checkpoint control, possibly via mediators unrelated to p21^WAF1.

Keywords: breast carcinoma; p34cdc2; p21WAF1; p53; prognosis

Abbreviations: bn, benign; CDK, cyclin dependent kinase; DFS, disease free survival; ER, oestrogen receptor; MPF, mitosis or maturation promoting factor; OS, overall survival; PR, progesterone receptor; TBS, Tris buffered saline; TC, tumour cytoplasm; TN, tumour nuclei

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