Search

Purpose: To create an easily applicable system based on a combination of the quantitative level of IMP3 (an oncofetal protein) and tumor stage to more accurately predict postoperative metastasis of localized renal cell carcinoma., Experimental Design: Three hundred sixty nine patients with localized renal cell carcinoma (without metastasis during nephrectomy) were investigated by the use of survival analysis. The expression of IMP3 was evaluated by immunohistochemistry and quantitated with a computerized image analyzer. Based on combining quantitative IMP3 results with tumor staging (QITS system), patients were divided into four distinct risk groups for the development of metastasis., Results: The four groups of patients in the QITS system showed significant differences in their metastasis-free (P<0.0001) and overall survivals (P<0.0001). Almost all patients of group IV with localized renal cell carcinomas developed metastasis and died after nephrectomy. The 5- and 10-year metastasis-free survival rates for the QITS groups were as follows: for group I, 97% and 91%; II, 62% and 55%; III, 46% and 19%; and IV, 17% and 4%, respectively. The 5- and 10-year overall survival rates for the QITS groups were as follows: for group I, 89% and 72%; II, 58% and 41%; III, 38% and 17%; and IV, 14% and 4%, respectively., Conclusions: The QITS is a simple and accurate system for the prediction of tumor metastasis. This system not only provides important prognostic information but also can be used at initial diagnosis of localized renal cell carcinoma to identify high-risk patients who may benefit from early systematic therapy.

Background: Whether an oncofetal protein, IMP3, can serve as a prognostic biomarker to predict metastasis for patients with localized papillary and chromophobe subtypes of renal cell carcinomas (RCCs) was investigated., Methods: The expression of IMP3 in 334 patients with primary papillary and chromophobe RCC from multiple medical centers was evaluated by immunohistochemistry. The 317 patients with localized papillary and chromophobe RCCs were further evaluated for outcome analyses., Results: IMP3 was significantly increased in a subset of localized papillary and chromophobe RCCs that subsequently metastasized. Patients with localized IMP3-positive tumors (n=33; 10%) were over 10 times more likely to metastasize (risk ratio [RR], 11.38; 95% confidence interval [CI], 5.40-23.96; P<.001) and were nearly twice as likely to die (RR, 1.91; 95% CI, 1.13-3.22; P=.016) compared with patients with localized IMP3 negative tumors. The 5-year metastasis-free and overall survival rates were 64% and 58% for patients with IMP3-positive localized papillary and chromophobe RCCs compared with 98% and 85% for patients with IMP3 negative tumors, respectively. In multivariable analysis adjusting for the TNM stage and nuclear grade, patients with IMP3-positive tumors were still over 10 times more likely to progress to distant metastasis (RR, 13.45; 95% CI, 6.00-30.14; P<.001) and were still nearly twice as likely die (RR, 1.95; 95% CI, 1.15-3.31; P=.013) compared with patients with IMP3-negative tumors., Conclusions: IMP3 is an independent prognostic biomarker that can be used to identify a subgroup of patients with localized papillary and chromophobe RCC who are at high risk for developing distant metastasis., (Copyright (c) 2008 American Cancer Society.)

Background: Distant metastasis is the main cause of death from renal-cell carcinoma, and the metastatic potential of tumours is often unpredictable. We aimed to investigate whether IMP3, an oncofetal RNA-binding protein, can be used as a biomarker to predict metastasis and prognosis of renal-cell carcinoma., Methods: We studied 501 primary and metastatic renal-cell tumours. 371 patients with localised primary tumours were further investigated by use of survival analysis. We assessed IMP3 expression in tumour tissues by immunohistochemistry, and IMP3 mRNA and protein expression in selected tissues by quantitative real-time PCR and western blot analysis., Findings: Compared with non-metastatic renal-cell tumours, IMP3 expression was greatly increased not only in metastatic tumours but also in a subset of primary tumours that were likely to subsequently develop metastases. Patients with primary localised tumours that did not express IMP3 had a longer metastasis-free survival and overall survival than did those with tumours expressing IMP3 (p<0.0001). Patients with IMP3-positive localised tumours had a much lower 5-year metastasis-free survival than did those with IMP3-negative tumours (for stage I tumours, 44% vs 98%, hazard ratio 17.18 [95% CI 7.82-37.78]; stage II, 41% vs 94%, 10.14 [3.46-29.68]; stage III, 16% vs 62%, 4.04 [2.23-7.31]). IMP3 expression was also associated with reduced 5-year overall survival (stage I, 32% vs 89%, 6.44 [3.63-11.42]; stage II, 41% vs 88%, 6.93 [2.63-18.27]; stage III, 14% vs 58%, 3.46 [1.98-6.05]). Multivariable analysis of IMP3 status (positive vs negative) in primary tumours showed hazard ratios of 5.84 (95% CI 3.60-9.49) for metastasis-free survival and 4.01 (2.66-6.05) for overall survival (both p<0.0001), which were much higher than hazard ratios associated with other independent risk factors., Interpretation: IMP3 is an independent prognostic marker that can be used at initial diagnosis of renal-cell carcinoma to identify patients who have a high potential to develop metastasis and who might benefit from early systemic treatment.