Discussion CRP is a standardized and widely used serum indicator of acute phase response in conditions such as acute inflammations, infections, tissue or organ necrosis, and malignancies. Some types of RCCs can induce sys temic inflammations by expressing various cytokines such as IL 1, tumor necrosis factor, and mostly IL 6. In The Right
Control Neratinib Before Time Runs Out vitro experimental studies showed some renal tumors themselves are actually capable of producing IL 6. Furthermore, RCC, especially of the aggressive phenotype, is often accompanied by tumor necrosis. Therefore, tumor status and aggressiveness can be directly reflected by the serum CRP levels of patients with AM RCC. Additionally, in case of other malignancies, CRP had been found to inhibit apoptosis of carcinoma cells, thereby directly regulating tumor cell growth and survival.
In fact, we often encounter cases of AM RCC in which the patients CRP level fluctuates in accordance with disease control and or progression. Several studies have also indicated that elevated CRP is a poor prognostic indicator for RCC. However, almost all the CRP cutoff points reported previously have been single values. These cutoff points range from 1. 0 to 10. 0 mg L and vary widely from study to study, despite the fact that in the majority of studies, the cutoff point was defined on the basis of the normal values. In the current study, we found that over 70% of the patients with AM RCC showed abnormal CRP values, with a relatively wide dynamic range of up to 200 mg L.
In fact, when we initially applied previously reported cutoff points to our patient cohort, we were unable to define any CRP based grouping system that could afford a ra tional assessment of survival risk. In this study, we initially determined the 2 CRP cutoff points 18. 0 and 67. 0 mg L in the nephrectomy patient cohort by means of ROC analysis. We then found that the CRP 3 grouping was a more suitable model for the risk stratifica tion of AM RCC patients because it was also applicable for patients who did not undergo nephrectomy. A number of prognostic parameters have been studied for patients with localized, metastatic, or all stage RCC C. Among the parameters defined for AM RCC, the most well established and validated ones are Memorial Sloan Kettering Cancer Center risk factors and predictors of short survival proposed by the NCCN practice guidelines.
In these models, however, CRP has not been enlisted as a significant fac tor. In our Cox models, we found that the risk factors associated with shorter survivals were high CRP level, low ECOG PS, and high number of metastatic organ sites. On the other hand, Hb and ALP levels were not found to be independent parameters. More over, sex, maximum tumor diameter, LDH and corrected calcium levels did not appear to be statistically signifi cant factors even in the univariate analyses.