The search for molecular markers that further advance our knowledge of the biology of renal cell carcinoma (RCC) and assist in evaluating the diagnosis and prognosis of patients remains the subject of intense investigation.

These types of studies have been greatly advanced by the emergence of gene array and tissue microarray technologies. Here, Parker and colleagues out of the Mayo Clinic report on the utility of survivin expression as a marker of prognosis in clear cell RCC. Survivin is an anti-apoptotic protein that demonstrates nuclear expression and was identified as being overexpressed in RCC as a consequence of genomic profiling studies.

Survivin expression was evaluated using computer assisted immunohistochemical analysis in 312 patients with clear cell RCC in a tissue microarray. Of these, 97 (31.3%) demonstrated increased expression of survivin. Overexpression of survivin in this study was classified as ? 2% of cells examined demonstrating increased expression.

Increased expression of survivin was associated with increased tumor size, more advanced tumor stage, increased tumor grade, the presence of coagulative necrosis, the presence of lymph node and distant metastases, and the presence of a venous tumor thrombus. Patients who had overexpression of survivin had an increase risk of death from RCC with a relative risk ratio (RR) of 5.3. The 5 year cancer specific survival for patients with survivin overexpression was 43% versus 87.2% in those without survivin overexpression. In a multivariate analysis that controlled for performance status, TNM stage, grade, and the Mayo SSIGN score, overexpression of survivin remained an independent risk factor for death from RCC. In a subset analysis of 273 patients with localized RCC, increased expression of survivin was associated with an increased risk of cancer progression following nephrectomy, with an RR of 3.9.

This study suggests that expression of the anti-apoptotic protein survivin is associated with a worse outcome in clear cell RCC. One criticism is the definition of overexpression of the protein, which in this study was greater than or equal to 2% of cells evaluated. Mean expression was only 2.3% for the entire population. One wonders of the biologic relevance and utility of a tissue marker that is not found in 98% of the cells in a given tumor.

Cancer 107(1): 37-45, 2006 - UroToday