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Background: Lymph node involvement is the most important prognostic factor in many solid cancers. Recently, we found that patients with esophageal and lung cancer carrying the C-reactive protein (CRP) 1846T/T genotype, which is associated with lower serum CRP levels, are more likely to have lymph node metastasis. We hypothesized that host CRP directly inhibits lymph node metastasis., Methods: We inoculated NR-S1M metastatic cells subcutaneously into the backs of C3H/HeN mice. Concurrently, 1 μg of recombinant mouse CRP or phosphate-buffered saline was injected subcutaneously every 3 days for 5 weeks, after which the mice were killed for evaluation. We evaluated lymph node metastasis and lymphangiogenesis in the implanted tumor by using immunohistochemical analysis with anti-pancytokeratin and antilymphatic vessel endothelial hyaluronan receptor-1 antibodies., Results: There was no substantial difference in tumor size between the 2 groups but the lymph nodes were smaller in the CRP group than the control group (P < .044). Immunohistochemical analysis confirmed inguinal lymph node metastasis in 70% (14/20) of control mice, but in only 30% (3/10) of mice in the CRP group. Moreover, the metastatic area within lymph nodes was less in the CRP group (P < .042) and tumoral lymphangiogenesis was decreased in the CRP group (P < .037)., Conclusion: CRP appears to inhibit tumoral lymphangiogenesis and lymph node metastasis in mice. These findings suggest that by inhibiting lymph node metastasis, CPR may have therapeutic potential for use against cancer., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: More than 40 % of patients with submucosal esophageal squamous cell carcinoma (ESCC) have lymph node metastasis. Furthermore, the potential presence of undetectable metastasis before treatment prompts surgeons to be aggressive with respect to lymph node dissection. Extending the indication for endoscopic resection, a minimally invasive treatment, to superficial ESCCs will require more accurate and individualized evaluation of lymph node metastasis., Methods: The study participants were 121 esophageal cancer patients who underwent curative surgery for thoracic submucosal ESCC at three Japanese hospitals. DNA was extracted from blood samples, and the C-reactive protein (CRP) 1846C>T genetic polymorphism (rs1205) was investigated using polymerase chain reaction-restriction fragment length polymorphism. We then evaluated the value of CRP 1846C>T polymorphism for diagnosis of lymph node metastasis., Results: Forty-nine (40 %) patients had lymph node metastasis. The CRP 1846 C/T genotype was C/C in 19 patients, C/T in 57 patients, and T/T in 45 patients. Fisher's exact analysis of the CRP 1846C>T polymorphism showed a significantly higher frequency of lymph node involvement with the T/T genotype. Univariate and multivariate logistic regression models revealed that patients carrying the 1846 T/T genotype had a significantly greater likelihood of developing lymph node metastasis (odds ratio >2.6). Combining the CRP 1846 C/T genotype with clinical diagnosis, mainly using CT, brought a negative predictive value of 80 % to diagnosing lymph node involvement., Conclusions: CRP genetic polymorphism may be a novel predictor of risk of lymph node metastasis in ESCC, which could enable better evaluation of the necessity for lymph node dissection.

C-reactive protein (CRP) produced locally within esophageal cancer is associated with the prognosis and the rate of recurrence. CRP genetic polymorphisms reportedly affect serum CRP concentrations; however, there are no reports of an association between genetic polymorphisms and tumoral CRP expression. This study enrolled 73 Japanese patients classified with Stage IIA-IV thoracic esophageal squamous cell cancer, and also investigated their CRP genetic polymorphisms using DNA extracted from their peripheral blood. The study then assessed the association between CRP genetic polymorphisms and tumoral CRP expression. The results revealed a significant association between the CRP 1846C>T genetic polymorphism and tumoral CRP expression. This finding suggests that tumoral CRP production controlled by CRP genetics significantly influences tumor behavior.

Purpose: Cancer cells reportedly produce C-reactive protein (CRP) locally within tumors. The aim of this study was to determine whether tumoral CRP is associated with clinical outcome and recurrence in thoracic esophageal squamous cell cancer., Methods: The subjects included 73 Japanese patients with thoracic esophageal squamous cell cancer (pathological Stage IIA-IV) that had not been treated preoperatively with either chemotherapy or radiotherapy. Tumoral CRP expression in resected specimens of tumor tissue was assessed by immunohistochemistry. The survival rate following surgery, the rates and patterns of recurrence, and the serum CRP levels before treatment and at recurrence were analyzed in patients with and without tumoral CRP expression., Results: Fifty-nine percent of the study participants (43/73) were positive for tumoral CRP expression, and the remaining 41% (30/73) were negative. No significant difference in clinicopathological factors was observed between the tumoral CRP-positive and CRP-negative groups; however, patients expressing tumoral CRP showed significantly poorer survival and recurrence rates. A multivariate analysis showed that tumoral CRP expression was an independent factor contributing to the likelihood of a poor outcome., Conclusion: Tumoral CRP is associated with a poor outcome in thoracic esophageal squamous cell cancer. Tumoral CRP could therefore be an important target for the treatment of this disease.

C-reactive protein (CRP) is one of the acute-phase proteins produced predominantly by hepatocytes in response to inflammation, and it has been widely reported that CRP genetic polymorphism is a risk factor for cardiovascular disease and ischemic stroke. In addition, we previously showed that the CRP 1846T/T genotype is related to lymph node metastasis in patients with esophageal cancer. In the present study, we investigated the correlation between CRP 1846C>T polymorphism and the clinicopathological characteristics of non-small cell lung cancer (NSCLC). The study participants were 146 Japanese patients who underwent curative surgery for NSCLC. DNA was extracted from tumor samples, and CRP1846C>T polymorphism was investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then correlated genotype with known clinicopathological factors. Five-year overall survival among patients with the CRP 1846T/T genotype was significantly lower than among those with the 1846C/C or C/T genotype (p = 0.002, p = 0.001; log-rank test). Multivariate Cox proportional hazard analysis revealed age, sex, pathological stage III, and 1846T/T (hazard ratio, 1.76; 95% confidence interval, 1.003-3.16; p = 0.049) to be independent factors affecting 5-year overall survival. These findings suggest the CRP 1846T/T genotype is an independent predictor of a poor prognosis in patients with NSCLC.

Background: Stress hyperglycemia refers to the transient hyperglycemia seen during illness and is usually restricted to patients without previous evidence of diabetes. The influence of genetics on surgery-induced hyperglycemia remains only partially understood., Methods: The study participants were Japanese patients treated for thoracic esophageal cancer with curative esophagectomy at Akita University Hospital between 2003 and 2007. We determined the associations between esophagectomy-induced stress hyperglycemia (> or =30 mg/dl increases in blood glucose during surgery) and genetic polymorphisms for C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, -beta, interferon-gamma, transforming growth factor-beta1, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-6 receptors, IL-10, IL-12beta, adiponectin, and peroxisome proliferator-activated receptor-gamma., Results: In 28 (46%) patients, blood glucose levels increased more than 30 mg/dl during surgery. Among the genetic polymorphisms tested, CRP -717C>T was significantly associated with stress hyperglycemia during esophagectomy. Multivariate logistic regression revealed that patients with the CRP -717T/T genotype had a significantly greater risk of developing surgery-induced hyperglycemia than those with the CRP -717C/T genotype. Stress hyperglycemia was also significantly associated with postoperative infectious complications and duration of intensive care unit stay., Conclusions: It is suggested that CRP -717 C>T genetic polymorphism may be a predictive factor for stress hyperglycemia in patients receiving esophagectomy for thoracic esophageal cancer.

Background: Little is known about how C-reactive protein (CRP) genetic polymorphisms influence the rise in serum CRP levels seen after surgery. The purpose of this study was to assess the association between CRP polymorphisms and acute-phase serum CRP levels after esophagectomy for thoracic esophageal cancer., Study Design: We enrolled 110 patients who underwent curative esophagectomy without neoadjuvant treatment between 2003 and 2008. Using peripheral blood samples collected from the patients, polymorphisms for CRP, tumor necrosis factor, interferon-gamma, tumor growth factor-beta1, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12beta were all investigated to determine which, if any, affect postoperative serum CRP levels and clinical outcomes., Results: Although preoperative serum CRP levels did not differ, 12 hours after esophagectomy, serum CRP levels were significantly higher in patients carrying the CRP 1059G/G genotype than in those with the 1059G/C genotype (111 +/- 35 mg/L versus 78 +/- 17 mg/L; p = 0.0266), and after 36 hours CRP levels remained higher in those with the 1059G/G genotype (217 +/- 63 mg/L versus 140 +/- 51 mg/L; p = 0.0020). Logistic regression models revealed that patients carrying the CRP 1059G/G genotype had a significantly higher likelihood of a postesophagectomy increase in serum CRP, although the CRP 1059G>C genetic polymorphism had no effect on clinical outcomes. None of the other cytokine genetic polymorphisms influenced postoperative serum CRP levels., Conclusions: Our findings suggest that the CRP 1059G>C genetic polymorphism is 1 determinant of serum CRP levels after major surgery.

Background: Lymph node involvement is the most important prognostic factor in thoracic esophageal cancer. A more accurate molecular technique for diagnosing lymph node metastasis and a better understanding of the molecular mechanisms governing lymph node metastasis would be highly desirable. The purpose of this study is to examine the association between inflammation-related genetic polymorphisms and lymph node metastasis., Methods: The study participants were 113 Japanese patients undergoing curative surgery for thoracic esophageal squamous cell cancer. DNA was extracted from blood samples and genetic polymorphisms in C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha and -beta, interferon (IFN)-gamma, transforming growth factor (TGF)- beta, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12beta were investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then assessed the association between inflammation-related genes and lymph node metastasis., Results: For CRP 1846C>T polymorphism, the frequency of the 1846T/T genotype was significantly higher in patients with lymph node metastasis (P = 0.0043), and the odds ratio (3.040) derived from logistic regression models indicated that the 1846T/T genotype significantly increases the likelihood of lymph node metastasis. In submucosal cancer, the utility of CRP 1846C>T polymorphism for predicting lymph node involvement was superior to usual methods (computed tomography and ultrasonography), with positive and negative predictive values of 69% and 75%, respectively., Conclusions: These findings suggest that CRP polymorphism is a potentially effective predictor of lymph node metastasis and may thus be useful for deciding on treatment strategy.

C-reactive protein (CRP) is one of the acute-phase proteins produced predominantly by hepatocytes in response to inflammation, and it has been widely reported that CRP genetic polymorphism is a risk factor for cardiovascular disease and ischemic stroke. In addition, we previously showed that the CRP 1846T/T genotype is related to lymph node metastasis in patients with esophageal cancer. In the present study, we investigated the correlation between CRP 1846C>T polymorphism and the clinicopathological characteristics of non-small cell lung cancer (NSCLC). The study participants were 146 Japanese patients who underwent curative surgery for NSCLC. DNA was extracted from tumor samples, and CRP1846C>T polymorphism was investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then correlated genotype with known clinicopathological factors. Five-year overall survival among patients with the CRP 1846T/T genotype was significantly lower than among those with the 1846C/C or C/T genotype ( p = 0.002, p = 0.001; log-rank test). Multivariate Cox proportional hazard analysis revealed age, sex, pathological stage III, and 1846T/T (hazard ratio, 1.76; 95% confidence interval, 1.003-3.16; p = 0.049) to be independent factors affecting 5-year overall survival. These findings suggest the CRP 1846T/T genotype is an independent predictor of a poor prognosis in patients with NSCLC. [ABSTRACT FROM AUTHOR]