Expession of pten, survivin and relation with apoptosis in the intraductal and invasive ductal breast carcinomas

Breast carcinoma is the most commonly seen carcinoma that is the second cause of death due to all carcinoma types. The genetic anomalies seen in breast carcinomas are, as seen in most of malign neoplasies, oncogene related chromosome translocations, deletions and mutations in tumor suppressor genes, various numerical chromosomal anomalies and other different genetic abnormalities. The determination of possible molecular genetic defects responsible for pathogenesis is necessary for better understanding of breast carcinomas and development of more effective treatment methods, as is in other malignities. PTEN chromosome, a tumor suppressor gene located in 10q23 locus, plays an important role in arrangement of signals required for cell growing and apoptosis. In case of absence or mutations of PTEN, tumor cells can protect themselves against apoptosis by the way of lipid signal transduction. PTEN gene mutations are seen various human cancers and related with advanced stage and poor prognosis in most cancers. It has also been suggested that a decrease in PTEN expression be related with poor prognosis and would be new prognostic determinant in breast carcinomas. Survivin, a member of apoptosis inhibitor protein family, plays role in arrangement of apoptosis, angiogenesis and cell division. Survivin is expressed in most carcinomas and related with resistance to chemotherapy, increased tumor recurrence and short survival. In this study, the relationship of PTEN and Survivin expression with clinico-pathologic prognostic parameters and apoptosis was investigated by the means of immunohistochemical method in 39 patients with invasive ductal breast carcinoma. A decrease or loss in PTEN expression was observed in an important portion (71.8%) of invasive ductal carcinomas. A negative correlation was detected only between PTEN expression and grade of hyperplasia (r:0.724 p:0.007), while there was no correlation with other clinicopathologic parameters such as age, tumor dimension, grade, lymph node metastasis, vascular invasion, Paget disease, ER, PR, c-erbB2 status and fibrocystic changes. In cases with invasive ductal carcinomas, strong staining with survivin was observed in 33.3% of cases, while there was weak staining in 61.6% and no staining in 5.1% of cases. No significant relationship between Survivin expression and clinicopathologic prognostic parameters was detected. Although survivin expression in IDC (1.28± 0.56) was fewer than survivin expression in DCI (ductal carcinoma in situ) (1.53±0.51), epithelial hyperplasia (1.57±0.51) and fibrocystic changes (1.55±0.51), differences were not statistically significant. In the groups of IDC and DCI more positive staining with TUNEL was detected as compared to other groups. From the clinicopathologic parameters, tumor dimension and vascular invasion showed positive correlation with apoptosis (r:0.636 p:0.007 and r:0.455 p:0.0016, respectively). PTEN, survivin expression and apoptosis did not show any correlation with each other in the IDC group. Our results suggested that a decrease in PTEN expression and increase in apoptosis be important in progression of IDC. Although survivin expression in IDC was lower than survivin expression in carcinoma in situ and benign lesions, it was not statistically significant. No relationship was found between apoptosis and PTEN or survivin expression. Further studies with large case series are needed to clarify importance of PTEN and survivin in progress of IDC and their relationship with apoptosis.