Expression Of Survivin In Breast Cancer Research Articles

The prognostic role of survivin expression in breast cancer: A systematic review and meta-analysis.

Breast cancer is a heterogeneous condition with variations in histopathological, genomic, and biological characteristics. Although clinicopathological prognostic factors and gene expression profiles are commonly used to guide treatment decisions in patients with breast cancer, there is still a need for new prognostic markers. One potential marker is survivin, a protein belonging to the apoptosis inhibitor family. However, studies examining the relationship between survivin and prognosis in breast cancer have yielded inconsistent results. This study aimed to evaluate the impact of survivin expression on the prognosis of breast cancer patients through a meta-analysis. Studies evaluating survivin expression were sourced from the PubMed, Embase, and Cochrane databases. We conducted a meta-analysis based on full-text articles that evaluated the relationship between survivin expression and survival by immunochemistry or polymerase chain reaction. The studies were initially divided into 2 groups based on the evaluation of overall survival (OS) and disease-free survival (DFS). Subsequently, each group was further categorized according to the method used to detect survivin expression. Statistical analyses for this study were conducted using Stata and JAMOVI. After screening with keywords, we identified 24 retrospective studies evaluating OS and 15 retrospective studies evaluating DFS, which were included in the analysis. We found that the studies in the meta-analysis were not heterogeneous, and this remained consistent when categorizing the groups by survivin expression detection. Survivin expression was associated with OS (HR 1.23, 95% CI 0.81-1.65) and DFS (HR 0.89, CI 0.42-1.36), indicating poor prognosis. This significant relationship between survivin expression and survival persisted when the studies were categorized by the detection method, either immunohistochemistry or polymerase chain reaction. In this study, we evaluated the prognostic significance of survivin expression in patients with breast cancer through a meta-analysis. These results support the use of survivin expression as a prognostic marker in breast cancer, potentially guiding treatment decisions.

HPV Status and Its Correlation with BCL2, p21, p53, Rb, and Survivin Expression in Breast Cancer in a Chinese Population.

Despite recent evidence, the role of human papillomavirus (HPV) in breast carcinogenesis is controversial. The correlations of HPV infection with the clinicopathological features of breast cancer and the expression of cell cycle/apoptosis-associated proteins have not been well elucidated. In this study, we sought to determine the prevalence of high-risk HPVs (HR-HPVs) infection and BCL2, p21, p53, Rb, and survivin expression in breast cancer patients and to investigate the relationship of HPV with these cancer-related proteins, in an attempt to clarify the potential mechanism of HPV in breast cancer pathogenesis. HPV presence in 81 fresh breast cancer tissues was determined by hybrid capture 2 (HC2) assay, and expression of BCL2, p21, p53, Rb, and survivin was detected by immunohistochemistry. Here we showed that fourteen (17.3%) patients were HR-HPV positive. HPV infection demonstrated no significant correlation with the clinicopathological characteristics of breast cancer. HPV-positive tumors showed significantly higher BCL2 and lower p53 expression than HPV-negative tumors. Expression of p21, Rb, and survivin was not associated with HPV status. Our results suggest a possible role of HR-HPV in breast cancer carcinogenesis, in which BCL2 and p53 may be involved.

Clinical significance of Smac and survivin expression in breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy

The second mitochondria‑derived activator of caspases (Smac), an antagonist of the inhibitor of apoptosis protein (IAP), increases chemosensitivity in vitro. Survivin, an IAP family member, mediates cancer cell survival and chemoresistance. The present study investigated the correlation between Smac and survivin expression in primary breast cancer, and the sensitivity to anthracycline during neoadjuvant chemotherapy (NAC). Pre‑treatment biopsies and post‑anthracycline treatment tumor sections were analyzed from 98 cases. Biomarker expression was evaluated by immunohistochemistry in tumor samples from clinical stage II and III anthracycline‑based NAC‑treated breast cancer. A univariate analysis indicated that the estrogen receptor (ER), Smac and survivin were significantly predictive of a pathological complete response (pCR) (P=0.004, 0.001 and 0.037, respectively) in pre‑chemotherapy samples. ER, Smac and survivin expression was also significant for pCR on the multivariate analysis (P=0.001, 0.031 and 0.012, respectively). An inverse association was identified between survivin and Smac expression (r=‑0.217, P=0.032; and r=‑0.335, P=0.003, respectively) prior to and following NAC. The patients with low survivin expression or high Smac expression had significantly longer disease‑free survival (DFS; P=0.012 and P=0.020, respectively) and overall survival (OS; P=0.01 and P=0.033, respectively) compared with the patients with high survivin or low Smac expression. Cox regression analyses demonstrated that survivin, Smac and clinical stage were independent predictors for DFS and OS. The present study indicated the significance of Smac and survivin in determining the breast cancer response to anthracycline‑based chemotherapy, and may permit further stratifying of pre‑chemotherapy patients to undertake more tailored treatments.

The Prognostic Significance of Survivin Expression in Breast Cancer

Purpose: Survivin is a member of the inhibitors of apoptosis family. It has recently comes into the limelight as a promising tumor marker, but many previous reports have shown controversial results regarding the significance and prognostic value of a survivin expression. In this study we determined the correlation between the survivin expression and the conventional prognostic markers and we also investigated the outcomes according to the localization of the survivin expression. Methods: Tissue microarray (TMA) blocks were made with formalin-fixed paraffin-embedded tissues from 185 breast cancer patients and the immunohistochemical staining was done using an anti-survivin antibody. Among these, 157 patients were available for a survivin expression. The conventional clinicopathologic features and overall survival were correlated with the localization of the survivin expression. Results: Survivin was expressed in 101 breast cancers (64.3%). A higher cytoplasmic survivin expression were noted in the older group (p=0.003), in the node-negative cancers (p= 0.012), in the earlier tumor stages (p=0.012) and in the cancers that had not been treated with adjuvant chemotherapy (p=0.014). On the contrary, a higher nuclear survivin expression was inversely correlated with an estrogen expression (p=0.006) and a progesterone receptor (p=0.043) expression. In terms of survival, a cytoplasmic expression was associated with improved overall survival (p=0.01) but a nuclear survivin expression was correlated with unfavorable overall survival (p=0.002). A high cytoplasmic to nuclear ratio of survivin was associated with improved overall survival (p=0.001) conversely, increased nuclear to cytoplasmic survivin ratio was correlated with unfavorable overall survival (p<0.0001). Multivariate analysis revealed that nuclear survivin expression (p= 0.001) and high nuclear to cytoplasmic survivin ratio (p=0.012) were independent predictor of overall survival. Conclusion: Survivin is frequently expressed in primary breast cancer. A cytoplasmic survivin expression is a good prognostic predictor for patients with axillary node negative early breast cancers and a nuclear survivin expression is a worse independent predictor of overall survival for patients with axillary node positive breast cancers.

Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1

Background: Survivin, a novel inhibitor of apoptosis, is one of the most cancer-specific proteins identified to date. In this study we (a) evaluated the association between survivin and HER2, vascular endothelial growth factor (VEGF) and uPA/PAI-1 expression and (b) defined its effect on clinical outcome in a large breast cancer patient cohort.Patients and methods: Survivin expression was measured by ELISA in primary breast cancer tissue extracts from 420 patients with long-term clinical follow-up.Results: Survivin was detected in 378 (90%) of the 420 primary breast cancer cases. Increased survivin levels were significantly associated with high nuclear grade (P < 0.0001), negative hormone receptor status (P = 0.0028), HER2 overexpression (P = 0.0094), VEGF expression (P < 0.0001), high uPA (P = 0.0002) and PAI-1 levels (P = 0.0002). Using the 25th percentile (1.4 ng/mg) as a cut-off point, patients expressing elevated survivin had a significantly worse disease-free survival (DFS: P = 0.0007, RR 1.97) and overall survival (OS: P = 0.0009, RR 2.11) compared with patients expressing lower levels of survivin. In multivariate analysis, this prognostic value of survivin was independent of both traditional and novel clinicopathologic factors for both DFS (P = 0.0076, RR 1.72) and OS (P = 0.0155, RR 1.76).Conclusions: The independent prognostic relevance of survivin, when combined with previous data from model systems implicating survivin in the inhibition of apoptosis, suggests that survivin may be a suitable target for future therapeutic strategies.

Mutations of the p53 gene and loss of heterozygosity at chromosome 17p13.1 are associated with increased survivin expression in breast cancer.

Expression of survivin, a member of the inhibitor-of-apoptosis (IAP) family, is elevated in fetal tissues and in various human cancers originating in the breast, lung, prostate, colon, pancreas, and stomach. Since overexpression of the survivin gene has been linked to poor patient survival in several cancers, survivin may be an important prognostic marker. Mechanisms up-regulating survivin gene expression in cancer are poorly understood. Recently, wild-type p53 was found to repress expression of the survivin gene by binding to the survivin promoter, thereby inhibiting promoter activity. Further, loss of heterozygosity (LOH) at 17p13 distal to the p53 gene is associated with more aggressive behavior of breast cancers. We therefore tested the hypothesis that not only p53 gene mutation but also LOH at 17p13 can up-regulate survivin expression in breast cancer. Survivin mRNA expression was greater in cancers than in uninvolved tissues (p < 0.0001). Mutations of the p53 gene were detected in 5 of 25 tumors; higher survivin gene expression was evident in these. LOH at the D17S938 locus (17p13.1) was found in 10 of 25 tumors, and most of these also showed increased survivin gene expression. Thus expression of survivin may be regulated not only by p53 but additionally by a putative tumor suppressor gene located at 17p13 distal to the p53 gene.

Modulation of survivin expression in breast cancer

Modulation of survivin expression in breast cancer