Μελέτη της έκφρασης της πρωτεΐνης p27_kip1 και της κινάσης p34_cdc2 σε εντοπισμένο πορογενές διηθητικό καρκίνωμα του μαστού με στόχο τη διερεύνηση πιθανής συσχέτισης με κλασσικούς προγνωστικούς παράγοντες καθώς και με την τελική έκβαση της νόσου

Abstract

This study investigates the expression of the cell cycle regulatory proteins p27kip1, p34cdc2 and p53 in node-negative invasive ductal breast carcinoma, investigates for potential correlation between them, or between these proteins and the classical clinicopathological parameters, and assesses their prognostic value in this neoplasm. Immunohistochemistry was applied on formalin-fixed (10%), paraffinembedded tissue sections from 94 breast carcinoma specimens using monoclonal antibodies for the p27kip1, p34cdc2 and p53 proteins. Adjacent benign epithelial breast tissue was available for examination in 82 cases for p27kip1 and p53 and 74 cases for p34cdc2. The median follow-up period was 72 months. p27kip1 positivity in the neoplastic and benign tissue was found in 61 (65%) and 75 (91%) cases respectively. Tumor cells were positive for p34cdc2 in 80 (85%) cases while the adjacent benign epithelium in 12 (15%) cases. Tumor p53 positivity was observed in 21 (23%) cases. A positive correlation was found between p27kip1 expression in tumor and estrogen and progesterone receptor status. There was also a significant positive association between p27kip1 and patients age 50 years or higher while low expression of p27kip1 was correlated with high tumor grade and greater tumor size. There was no correlation between p27kip1 immunoreactivity and disease free survival (DFS) or overall survival (OS). High levels of nuclear p34cdc2 in the neoplastic tissue were associated with higher histological grade and p53 expression but were not correlated with DFS or OS. Cytoplasmic p34cdc2 expression in tumor was associated with high tumor grade and DFS. p34cdc2 expression by the normal breast tissue independently predicted patient outcome. Expression of p53 was associated with high tumor grade and negative steroid receptors, but was not correlated with DFS or OS. Based on these findings, alterations of the proteins p27kip1, p34cdc2 and p53 are involved in cell cycle deregulation and probably contribute in breast tumorigenesis. Expression of p27kip1, p34cdc2 and p53 in nodenegative breast carcinoma does not predict disease outcome, while there is an association between the presence of p34cdc2 in normal breast tissue and prognosis. The relationship of p34cdc2 and p53 indicates an implication of p53 in the G2-M cell cycle checkpoint control.