engleski

Association of BIRC5 polymorphisms and survivin expression with clinicopathological characteristics of breast cancer patients

Breast cancer (BC) is the most common malignancy in women. Common risk factors are age, hormonal factors, reproductive and menstrual history, exposure to radiation, obesity and genetic background. Genetic variation can affect both susceptibility and prognosis. Survivin, encoded by BIRC5 gene (baculoviral IAP repeat containing 5), belongs to the family of inhibitors of apoptosis proteins (IAPs). In mammalian cells it participates in the control of mitosis, apoptosis regulation and cellular stress response. Its expression is increased in almost all cancer types. The aim of this study was to investigate the role of BIRC5 polymorphisms in BC and to correlate survivin expression with various clinicopathological characteristics including age of onset, time since operation, histological grade, tumor type and size, lymph node status, estrogen, progesterone, Her2 and Ki67 status. Blood and FFPE tumor tissue samples were collected from 26 Croatian BC patients. Majority had invasive ductal carcinoma (81.5%). Survivin expression was determined immunohistochemically and scored between 1 and 3 taking into account percentage of positive cells and staining intensity. BIRC5 promoter, coding region and 3’UTR were genotyped using high resolution melting analysis and Sanger sequencing. Genomic DNA from 74 healthy women was used as control. Numbers of samples with survivin expression with a score 1, 2 and 3 were 9 (33.3%), 11 (40.7%) and 7 (25.9%), respectively. Most patients had nuclear survivin staining (92.6%). High survivin expression was associated with negative ER status (p=0.007) and positive Ki67 expression (p=0.032). Ki67 expression was also positively associated with histological grade (p=0.0009). Fourteen polymorphisms were found in BC samples, located mostly in promoter and 3’UTR. There were no significant differences in polymorphisms’ frequencies between BC and control samples. However, age of onset was associated with five BIRC5 polymorphisms (c.-1547C>T, c.-644T>C, c.-241C>T, c.9386T>C and c.9809T>C). This was the first study investigating the possible role of BIRC5 polymorphisms in breast cancer etiology conducted in Croatia. Although no association of any of BIRC5 polymorphism with BC or level of survivin expression was observed, several polymorphisms were associated with the age of onset. Further research with a larger sample size is needed to assess the significance of BIRC5 polymorphisms and survivin expression as predictive/prognostic biomarkers for BC.

BIRC5 ; survivin ; polymorphisms ; expression ; immunohistochemistry ; breast cancer

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