BACKGROUND: Metastatic potential of localized renal cell carcinoma (RCC) is often unpredictable. In this study, we used quantitative analysis of the immunohistochemistry (IHC) to investigate whether the RNA binding protein (IMP3), an oncofetal protein, can serve as a new biomarker to predict metastasis and prognosis of RCC.
METHODS: 371 patients with localized RCCs (stage I: N=216; II: N=64; III: N=91) from three participating institutions were investigated by survival analysis. The expression of IMP3 was evaluated by IHC with a computerized image analyzer (ACIS). IMP3 expression in RCCs was considered to be negative [average ACIS value/case (ACISV): <1] and positive (ACISV: 1; low levels of expression: ACISV = 1 to 10, and high levels of expression: ACISV = >10).
RESULTS: The expression of IMP3 was only observed in the cytoplasm of tumor cells but not in benign tissue adjacent to cancer. Kaplan-Meier plots in all patients and in patients separated in each stage showed that patients with IMP3-negative RCCs (ACISV = 0.08 0.09) had a significantly longer metastasis-free and overall survival than did those with IMP3-positive RCCs (ACISV =16.9 24.8, P<0.0001). In patients whose localized RCCs were negative for IMP3, the 5-year metastasis-free and overall survival rates were 98% and 89% (stage I), 94% and 88% (stage II), and 62% and 58% (stage III) respectively, whereas in patients with IMP3 positive RCCs, the metastatic free and overall survival rates were 44% and 32% (stage I), 41% and 41% (stage II), and 16% and 14% (stage III) respectively. Patients with low levels of IMP3 in their tumors (ACISV = 3.9 2.5) were also had better metastasis-free and overall survival rates than did those with high levels of IMP3 (ACISV = 40.6 29.4, P<0.001). Multivariable analysis showed that IMP3 status in primary RCCs was a strong independent predictor of clinical outcome. The hazard ratios were 6.08 (metastasis-free survival, P<0.0001) and 4.06 (overall survival, P<0.0001), which were much higher than hazard ratios associated with other independent risk factors.
CONCLUSIONS: IMP3 is an excellent independent prognostic marker that can be used at the time of initial diagnosis of RCC to identify patients who have a high potential to develop metastasis and who might benefit from early systemic therapy.