C-Reactive Protein as a Clinically Useful Biomarker of Metastasis of Renal Cell Carcinoma
ABSTRACT C-reactive protein (CRP) is an acute-phase reactant that can increase dramatically in response to a variety of pathologic states. Elevated pre- and postoperative CRP levels have been associated with an increased tumor burden and metastasis in kidney cancer. We report on a case that serves to highlight a potentially novel use for CRP monitoring in the postoperative management of renal cell carcinoma. Recently, we treated a patient who presented with a localized renal cell carcinoma and an elevated preoperative CRP level. Surgical pathology demonstrated negative surgical margins and absence of nodal metastasis. Postoperatively, the patient's serum CRP levels remained relatively low, consistent with his continued negative staging on CT scans. However, at 6 months postoperatively, the patient's CRP level increased 13-fold. His subsequent CT scan revealed "multiple pulmonary nodules consistent with progression of metastatic disease." This case demonstrates the potential for monitoring CRP in addition to, or instead of, standard restaging imaging.
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ABSTRACT: Elevations in C-reactive protein (CRP) levels predict metastasis and mortality in a number of malignancies. However, the impact of non-malignant factors on CRP levels in patients with cancer remains unknown. To address this issue, we conducted an investigation of the National Social Life, Health, and Aging Project (NSHAP) cohort. NSHAP participants with a history of malignancy were included. The 222-participant cohort was subdivided by CRP levels into low-risk (CRP <3 mg/L) and high-risk (CRP ≥3 mg/L) groups. Univariate and multivariate binary logistic regression analyses examined the impact of variables spanning social factors, demographic characteristics, and past medical history on high-risk CRP levels. Of the cohort, 42.3% exhibited high-risk CRP levels. These participants were more likely to be unmarried (p = 0.013), to be a racial/ethnic minority (p = 0.012), to not use HMG-CoA reductase inhibitor (statin) medications (p = 0.032), and to be obese (p = 0.002). On multivariate logistic regression analysis, these variables were also significant predictors of high-risk CRP levels. For example, compared with participants who had a normal body mass index (BMI), obese participants were nearly 5 times more likely (odds ratio 5.725; 95% CI 1.848, 12.079; p = 0.001) to exhibit high-risk CRP levels. CRP remains an important prognostic biomarker in the management of known malignancies. However, patients with a known history of cancer can also exhibit elevated CRP levels due to non-malignant factors such as race and ethnicity, statin use, marital status, and BMI. Consequently, further studies are needed to assess the predictive potential of CRP levels for cancer prognostication in the face of these social and biologic variables before use of this biomarker is widely adopted in clinical practice.Molecular Diagnosis & Therapy 10/2010; 14(5):295-303. DOI:10.2165/11539670-000000000-00000 · 2.59 Impact Factor
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ABSTRACT: C-reactive protein (CRP), an acute phase reactant, is a non-specific marker of inflammation. Elevations in CRP levels are linked with trauma, infection, autoimmune disease, malignancy, and lifestyle factors, such as smoking and obesity. Previously, we noted a significant association between the preoperative CRP level, 1-year relapse-free survival, and 1-year overall relative survival in patients with localized renal cell carcinoma (RCC). This study sought to determine what effect, if any, lifestyle factors have on the prognostic value of preoperative CRP level for overall survival in individuals with localized RCC. 257 patients with localized RCC who underwent nephrectomy were included in the study. Patients were enrolled between November 2006 and February 2010. The impact of tumor characteristics, lifestyle factors, and preoperative CRP level on overall survival was assessed through univariate and multivariate analyses. During the study, 15.2% of patients died. Univariate analysis found that tumor size (p < 0.001), tumor stage (p < 0.001), Fuhrman nuclear grade (p < 0.001), Charlson Comorbidity Index score (p < 0.001), smoking status (p = 0.038), and preoperative CRP level (p < 0.001) were significantly associated with overall survival. Only the preoperative CRP level (odds ratio 1.035; 95% confidence interval 1.007, 1.064) remained significantly associated with overall survival upon multivariate analysis. Prognostic tools serve an important role in cancer management. Thirty percent of patients with localized RCC ultimately develop metastatic disease despite having potentially curative nephrectomy. Previous research has identified the preoperative CRP level as a significant predictor of overall survival in patients with localized RCC. This study demonstrated that the CRP level remained a robust predictive tool when the analysis was controlled for lifestyle factors, including smoking and obesity. Consequently, clinicians should consider taking preoperative CRP levels into account when treating patients with localized RCC.Molecular Diagnosis & Therapy 07/2011; 15(4):229-34. DOI:10.2165/11534900-000000000-00000 · 2.59 Impact Factor
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ABSTRACT: Serum C-reactive protein has been shown to have prognostic value in localized and metastatic renal cell carcinoma. However, the prognostic value of intratumor C-reactive protein remains unknown. A total of 95 patients with resected, clinically localized (T1-T4N0M0) clear cell renal cell carcinoma were followed postoperatively. Intratumor C-reactive protein expression was assessed in surgical specimens using immunohistochemical analysis. Patients were categorized by staining intensity into low risk (staining 0 to 1), intermediate risk (staining 2) and high risk (staining 3) groups. Kaplan-Meier and multivariate Cox regression analyses were used to examine overall survival across patient and disease characteristics. Variables examined in multivariate Cox regression analysis included T stage, Fuhrman nuclear grade, tumor size, preoperative serum C-reactive protein and intratumor C-reactive protein staining. Followup extended up to 46 months with a mean (SD) of 29.8 (11.0) months. Twelve patients (12.6%) died during followup. Of all tumors 49.5%, 25.3% and 25.3% were graded by intratumor C-reactive protein staining as low risk (0 to 1), intermediate risk (2) and high risk (3), respectively. After controlling for variables significant on univariate analysis, patients in the high risk (3) group experienced a 27-fold increased risk of overall mortality compared to those in the low risk (0-1) group (HR 27.767, 95% CI 1.488-518.182). After adjusting for tumor staining, preoperative serum C-reactive protein was not a significant predictor of overall survival (p = 0.741). Intratumor C-reactive protein may be a robust biomarker of prognosis in patients with localized renal cell carcinoma.The Journal of urology 08/2011; 186(4):1213-7. DOI:10.1016/j.juro.2011.06.014 · 3.75 Impact Factor