EXPRESSION OF THE G2M CHECKPOINT REGULATOR CYCLIN B1 IN BREAST CANCER AND ITS CORRELATION WITH PROGNOSTIC PARAMETERS

Abstract

Background: Breast cancer is the most common malignancy in Egyptian females. A wealth of literature is available on various diagnostic and prognostic parameters including clinical, pathological and biological factors. The present study focuses on markers of cell cycle proteins as cyclin B1 and parameters of cell cycle kinetics, related growth factors and tissue polyamines in relation to hormone receptor status.Patients and methods: A total of 102 females made the subject of the study, 72 females with breast cancer, 14 with benign lesions and 16 healthy subjects serving as controls for serum arameters. Normal breast tissue served as control for breast cancer tissues. Tissue polyamines were measured by HPLC. yclin B1 was measured by Flow cytometry (FCM) and Western Blotting (WB). Insulin-like Growth factor 1(IGF1) was easured by enzyme immunoassay (EIA). Tumor markers (CEA and CA 15.3), estradiol and progesterone levels were measured by microparticle enzyme immune assay (MEIA).Results: Cyclin B1 was detected in 17/34 (50%) of the cases tested by FCM and only in 10% of the cases evaluated by WB. Cyclin B1 positivity tended to be associated with high grade tumors. The mean percentage of cyclin B1 positivity was higher in aneuploid tumors than in diploid ones, as well as in tumors with ≥ 10% S-phase fraction (SPF) compared to those with < 10 % SPF. Cyclin B1 positivity was significantly associated with patients of high G2/M phase (p=0.05). Cell cycle analysis showed that ER-ve tumors were significantly associated with high SPF. Tissues polyamines showed significantly increased levels when compared to both benign and normal groups (p< 0.001). Polyamines showed a significant association with ER status (p= 0.04), tumor size (p=0.04) and histopathologic type (p= 0.05). Serum IGF 1 showed insignificant increased level in breast cancer patients less than 45 yrs when compared to the age matched control group. Serum estrogen level showed no change in the breast cancer patients ≥ 45yrs compared to age matched control group, while progesterone level was significantly lower (p< 0.02) in breast cancer patients less than 45yrs old compared to age matched benign and control groups. Serum CEA and CA 15.3 showed significant increase in the breast cancer patients < 45yrs old compared to age matched benign and control groups (p=0.03 and 0.06, respectively).Conclusion: Polyamines proved value as markers of proliferative activity of breast cancer but their testing needs further standardization. Cyclin B1 is associated with aggressive tumors. Its assessment by FCM proved superior to western blotting. IGF1 might be better used to assess tumor recurrence and monitor cancer patients, and its use needs further evaluation. This study may contribute to understanding breast cancer cell growth biology in Egyptian females in view of improving therapeutic and chemopreventive strategies.