engleski

Correlation of BIRC5 polymorphisms and survivin expression with clinicopathological characteristics of breast cancer patients from Croatia

INTRODUCTION: Breast cancer (BC) is one of the most common malignancies among women. Common risk factors for BC are age, hormonal factors, reproductive and menstrual history, exposure to radiation, obesity and genetic background. Genetic variation can affect both susceptibility and prognosis of BC. 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 types of cancers. The aim of this study was to investigate the role of BIRC5 polymorphisms in BC and to correlate survivin expression with various clinicopathological characteristics. PATIENTS AND METHODS: Blood and FFPE tumor tissue samples were collected from 26 BC patients from Croatia. Majority of patients had invasive ductal carcinoma (81.5%). Survivin expression was determined immunohistochemically and it was scored between 1 and 3 taking into account percentage of positive cells and staining intensity. Promoter, coding region and 3’UTR of BIRC5 were genotyped using high resolution melting analysis followed by Sanger sequencing. As a control DNA isolated from blood from 74 healthy women was used. BIRC5 polymorphisms and survivin expression were correlated with age of onset, time since operation, histological grade and type, tumor size, lymph node status, estrogen, progesterone, Her2 and Ki67 status. RESULTS: 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 significantly associated with negative ER status (p=0.007) and positive Ki67 expression (p=0.032). Ki67 expression was also positively correlated with histological grade (p=0.0009). Fourteen polymorphisms were found in BC samples, located mostly in promoter and 3’UTR of BIRC5. There was no significant difference in the distribution of polymorphisms between BC and control samples. Among clinicopathological characteristics of BC patients, age of onset was associated with five BIRC5 polymorphisms. CONCLUSION: This was the first study investigating the possible role of BIRC5 polymorphisms in breast cancer etiology conducted in Croatia. In this preliminary study no association of any of BIRC5 polymorphism with BC or level of survivin expression was observed. However, several BIRC5 polymorphisms were associated with the age of onset. To assess the significance of BIRC5 polymorphisms and survivin expression as predictive and prognostic biomarkers for BC further research is needed with a larger sample size.

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

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