C-Reactive Protein: A Marker for Aggressive Hepatocellular Carcinoma
C-Reactive Protein: A Marker for Aggressive Hepatocellular Carcinoma
Abstract & Commentary
William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC, is Editor for Clinical Oncology Alert
Synopsis: C-reactive protein (CRP) is an acute phase reactant produced by hepatocytes in response to proinflammatory cytokines. It has been shown to be a prognostic indicator in cardiovascular and various neoplastic processes. Inasmuch as another hepatocyte synthesized inflammatory factor (intercellular adhesion molecule-1) was earlier shown to correlate with advanced hepatocellular carcinoma, Hashimoto and colleagues performed a retrospective analysis to test whether CRP would likewise be a useful clinical marker. They found a definite correlation of preoperative CRP levels with disease recurrence and survival, and when combined with serum albumin and platelet number, a useful prognostic scoring system was proposed.
Source: Hashimoto K, et al. Cancer. 2005;103:1856-1864.
C-reactive protein (CRP) is an acute phase reactant that is synthesized by hepatocytes in response to inflammatory signals. Hashimoto and colleagues at Fukuoka City Hospital in Japan performed a retrospective analysis of 141 patients who underwent curative resection for hepatocellular carcinoma (HCC). Clinicopathologic variables were compared between patients with serum CRP levels > 1 mg/dL (n = 22 patients; CRP-positive group) and patients with serum CRP levels < 1 mg/dL (n = 119 patients; CRP-negative group).
There was a significant correlation between the preoperative serum CRP level and tumor size. Invasion to the portal vein in the CRP-positive group was significantly more frequent than that in the CRP-negative group. Within 1 year after surgery, tumor recurred in 75.3% of the patients in the CRP-positive group. The overall survival and recurrence-free survival were significantly better for those in the CRP-negative group. On multivariate analysis, the preoperative serum CRP level was selected as one of the unfavorable indicators regarding survival and recurrence. When CRP levels, albumin levels (less than 4 g/dL), and platelet count (less than 120,000 cells/mm3) were scored as a combined index, the total score demonstrated a good stratification value for survival after hepatic resection.
Comment by William B. Ershler, MD
HCC is a common malignancy worldwide, particularly in Asia and Africa, but it also has increasing incidence in Western countries.1 The single best chance for long-term survival is surgical resection, and yet, as witnessed by this series, a significant percentage of those taken to surgery with curative intention will have the disease recur, typically within the first year or 2 after resection. Hashimoto et al have presented cogent data that preoperative CRP levels predict those likely to have recurrent disease. In fact, in combination with serum albumin levels and platelet counts, a new scoring system is proposed that appears to have even greater predictive value.
CRP has been shown to correlate significantly with adverse outcomes for other tumor types, most notably esophageal (2), gastric (3), and colon cancer (4), as well as multiple myeloma (5), and malignant fibrous histiocytoma (6); but this may be the first report with HCC. In this series, for those with elevated levels the recurrence rate was 75% within one year, significantly greater than the approximate 20% in the CRP-negative group. Thus, preoperative CRP levels may help identify at risk individuals who would be candidates for neoadjuvant or adjuvant chemotherapy. Of course, this presumes the availability of effective drugs for HCC and, unfortunately, no agents have demonstrated clear-cut benefit when measurable disease is present or in the adjuvant setting. Thus CRP, a readily available and inexpensive measure, may prove to be of significant clinical value in identifying high-risk HCC patients prior to resection.
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