Do the Survivin (BIRC5) Splice Variants Modulate or Add to the Prognostic Value of Total Survivin in Breast Cancer?

Abstract

Background: A total of 4 additional splice variants (survivin-⌬Ex3, survivin 2␣, survivin-2B, and survivin-3B) have been described for survivin [baculoviral IAP repeat-containing protein (BIRC-5), approved gene symbol BIRC5], which has been implicated in both inhibition of apoptosis and regulation in mitosis in many tumor types. In this study, we assessed whether the survivin splice variants modulate or add to the prognostic value of total survivin in breast cancer. Methods: With quantitative reverse transcription-PCR, we measured mRNA concentrations of survivin and all variants in tumor tissue from 275 patients with breast cancer and associated these with clinicopathologic characteristics and relapse-free survival. Results: Total survivin, survivin-⌬Ex3, and survivin 2␣ mRNA levels were associated with young age and ductal histology. Total survivin and survivin-⌬Ex3 were highest in samples with advanced histological grade, whereas patients with 4 -9 involved lymph nodes expressed less survivin-2B mRNA than those with 1-3 involved nodes. All variants were higher in tumors negative for steroid hormone receptors. Total survivin, survivin 2␣, and survivin-3B were associated with poor relapse-free survival in univariate analyses. Survivin 2␣ and survivin-3B added to the prognostic value of total survivin in multivariate analyses. In addition, the prog-

Association of survivin splice variants with prognosis and treatment of breast cancer

“…Real time qPCR Tumor grade, estrogen receptors, lymph nodes High expression sur3b tumors had shorter OS and DFS Span et al [23] wt, sur2b, surΔΕx3, sur3b, sur2a…”

“…In addition, increased expression of survivin-3b after one course of docetaxel/epirubicin treatment was associated with reduced disease free survival (DFS) of breast cancer patients. Indeed, high survivin-3b expression tumors had a shorter overall and DFS [23] . All these findings suggest that the role of survivin is probably therapy specific in resistance.…”

“…Span et al [23] 2006 discovered that survivin-wild type, survivin-2a, and survivin-3b were associated in patient samples with poor relapse free survival. Survivin, survivin-ΔEx3 and survivin-2a variants were associated with younger age, advanced histological grade and steroid hormone-receptor-negative tumors, all factors that indicate poor prognosis for a breast cancer patient.…”

“…The data in this study confirm that some of the splice variants interact with each other and modify the prognosis of the patients. Specifically, high expression of the survivin-2a and survivin3b, in addition to survivin indicate a poorer prognosis and the prognostic value of survivin is strongest in the presence of higher concentrations of these variants [23] . In the report of Ryan et al [10] , both wild-type survivin and survivin-ΔEx3 mRNA correlated moderately with apoptosis in patient samples.…”

Survivin is expressed in early hepatocellular carcinoma and surrounding hepatitis tissue

“…Survivin, a member of the recently described iaP family, is characterized by a unique structure with a single Bir and no zinc-binding domain (14). it is undetectable in terminally differentiated adult tissues, but becomes notably expressed in the most common human cancers, including esophageal, stomach, colorectal, breast and pancreatic carcinoma (15)(16)(17)(18)(19).…”