Expression of cyclin-D1 and apoptosis regulating protein BCL-2 in infiltrating ductal breast carcinoma [NOS]

ABSTRACT

Breast carcinoma is the most frequently diagnosed carcinoma affecting females contributing for about 30% of all female cancers in Egypt Estrogen and progesterone receptors [ER and PR] have been used as tools to identify patients eligible for adjuvant treatments, yet they present some limits, as the existence of dysfunctional receptors made some ER positive tumours non-responsive to antiestrogen therapy. In breast cancer, Bcl-2 expression has been reported to be associated with better outcomes in patients treated with either hormone- or chemo-therapy. Also, the expression of the protein cyclin D1 is detected in up to 50% of primary breast cancers. Cyclin D1 over expression has been strongly associated with well-differentiated, estrogen receptor-positive ductal tumors The present work aimed at determining the expression of cyclin D1 and bcl-2 proteins in some cases of infiltrating breast ductal carcinoma not otherwise specified [NOS,] and to assess any possible relationship between each marker and estrogen receptor status of the tumour tissue. Thirty cases of infiltrating ductal carcinoma [IDC], not otherwise specified [NOS], 17 cases of which were associated with axillary lymph node metastases, in addition to 5 cases of florid epithelial hyperplasia were included in the study. For all studied cases routine histopathological examination and immunohistochemical staining by ER, bcl-2 and cyclin D1 antibodies were done. ER status showed positive ER immunoreactivity in 21 cases [70%] out of 30 [2 cases/2 were grade I, 14 cases /18 were grade II and 5 cases/10 were grade III]. Positive Bcl-2 immunoreactivity was observed in 23 cases of the 30 IDC cases [76.66%] 2 cases/2 were of grade I, 16 cases/18 of grade II and 5 cases/10 were of grade III. o A statistically significant relation was found between bcl-2 immunoreactivity and ER expression in the malignant cases [p<0.0001]. Cyclin D1 expression was detected in 20 cases of IDC [66.66%], staining was nuclear and diffuse 2 cases out of 2 of WD carcinoma and 4 cases of MD carcinoma out of 18 showed strong staining [score 1], 10 cases of MD carcinoma out of 18 showed moderate staining [score 2], and 4 cases out of 10 of PD carcinoma showed weak staining [score 3].All the cyclin D1 positive 20 cases were also ER positive [100%]. A statistically significant relation was found between cyclin D1 immunoreactivity and ER expression [p<0.0004]. Bcl-2 was strongly associated with ER positivity in the majority of breast carcinomas but over expression of cyclin D1 protein correlated with poor prognosis and it was demonstrated that its over expression distinguished malignant breast carcinomas from premalignant breast lesions as the less differentiated high grade tumors exhibited a more intense nuclear stain and the non-neoplastic epithelial components were not stained