Determination of the prognostic value of cyclin D1, C-erb B-2, Ki-67 and the nucleolar organizer regions (AgNORs) in breast cancer Ragaey R. Fahmy M.D. Department of Pathology, Benha Faculty of Medicine, Benha University Abstract: Four different types of measurements of prognostic factors (cyclin D1, C-erb B-2, Ki-67 and AgNORs) were applied to a series of 70 breast lesions representing, 35 cases of invasive ductal carcinoma, 10 cases of invasive lobular carcinoma, 5 cases of tubular carcinoma, 10 cases of ductal carcinoma in situ, 10 cases of atypical ductal hyperplasia (ADH), in addition to 7 cases of normal breast tissue as a control, in combination with clinicopathological parameters to evaluate their prognostic significance in breast cancer. Expression of cyclin D1 is negative in atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). However, in 29/50 (58%) of invasive cancer breast, positive expression of cyclin D1 was observed. There is a significant association was observed between cyclin D1 expression and distant metastasis, recurrence, and five-year survival rate of the patients with breast cancer. There is also a significant correlation between C-erb B-2 expression and distant metastases, recurrence and 5-year survival rate. The Ki-67 label index and AgNORs count was found to correlate significantly and increased gradually with progression of breast lesions. The AgNORs size, shape and distribution was found to show a characteristic difference between benign, atypical and malignant groups. Malignant cells were characterized by an irregularly scattered distribution of AgNORs and by a pleomorphic size and shape of the dots in comparison to the round, uniform and regular size and shape of the AgNORs dots in benign lesions. Positive expression of cyclin D1, C-erb B-2, Ki-67 and high AgNORs score could be serve as a poor prognostic markers for patients with breast carcinoma independent of nodal metastases and clinical parameters, also expression of cyclin D1 could help in diagnosis of early invasion of breast carcinoma. Research in Benha M.J. 25 (1)(2008): 375–394