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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- "IL-6, produced in part by RCC cells, is a known mediator of inflammation and the primary inducer of CRP production in both hepatocytes and RCC tumor cells. Consequently, elevations in the IL-6/CRP axis have been strongly linked to tumor grade, tumor size and metastases. These correlations confirm the attribution of poor outcomes to the tumor. "
ABSTRACT: The modified Glasgow prognostic Score (mGPS) incorporates C-reactive protein and albumin as a clinically useful marker of tumor behavior. The ability of the mGPS to predict metastasis in localized renal cell carcinoma (RCC) remains unknown in an external validation cohort. Patients with clinically localized clear cell RCC were followed for 1 year post-operatively. Metastases were identified radiologically. Patients were categorized by mGPS score as low-risk (mGPS = 0 points), intermediate-risk (mGPS = 1 point) and high-risk (mGPS = 2 points). Univariate, Kaplan-Meier and multivariate Cox regression analyses examined Recurrence -free survival (RFS) across patient and disease characteristics. Of the 129 patients in this study, 23.3% developed metastases. Of low, intermediate and high risk patients, 10.1%, 38.9% and 89.9% recurred during the study. After accounting for various patient and tumor characteristics in multivariate analysis including stage and grade, only mGPS was significantly associated with RFS. Compared with low-risk patients, intermediate- and high-risk patients experienced a 4-fold (hazard ratios [HR]: 4.035, 95% confidence interval [CI]: 1.312-12.415, P = 0.015) and 7-fold (HR: 7.012, 95% CI: 2.126-23.123 P < 0.001) risk of metastasis, respectively. mGPS is a robust predictor of metastasis following potentially curative nephrectomy for localized RCC. Clinicians may consider mGPS as an adjunct to identify high-risk patients for possible enrollment into clinical trials or for patient counseling.Indian Journal of Urology 03/2014; 30(1):33-7. DOI:10.4103/0970-1591.124203
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ABSTRACT: Tumor cells exhibit at least two distinct modes of migration when invading the 3D environment. A single tumor cell's invasive strategy follows either mesenchymal or amoeboid patterns. Certain cell types can use both modes of invasiveness and undergo transitions between them. This work outlines the signaling pathways involved in mesenchymal and amoeboid types of tumor cell motility and summarizes the molecular mechanisms that are involved in transitions between them. The focus is on the signaling of the Rho family of small GTPases that regulate the cytoskeleton-dependent processes taking place during the cell migration. The multiple interactions among the Rho family of proteins, their regulators and effectors are thought to be the key determinants of the particular type of invasiveness. Mesenchymal and amoeboid invasive strategies display different adhesive and proteolytical interactions with the surrounding matrix and the alterations influencing these interactions can also lead to the transitions.Cellular and Molecular Life Sciences CMLS 09/2009; 67(1):63-71. DOI:10.1007/s00018-009-0132-1 · 5.81 Impact Factor
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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 · 2.89 Impact Factor