Evaluation of the diagnostic value of serum tumor markers, and fecal k-ras and p53 gene mutations for pancreatic cancer.

Objective: To evaluate the diagnostic value for pancreatic cancer of four serum tumor markers, carbohydrate antigen (CA) 199, CA242, CA50 and carcino-embryonic antigen (CEA), and fecal k-ras and p53 gene mutations.

Methods: From February 2002 to March 2004, 136 patients were consecutively diagnosed with pancreatic cancer in the three participating medical centers. The diagnosis was confirmed by pathology in 53 patients, of whom five were excluded because they did not have measurement of serum tumor marker. The remaining 48 patients comprised the case group in the study. Ninety-six patients with benign digestive diseases diagnosed during the same period were recruited as control subjects. They were matched by sex and age. In both groups, serum CA199, CA242, CA50 and CEA were measured by ELISA, and fecal k-ras and p53 gene mutations were measured by PCR-restriction fragment length polymorphism and PCR-single strand conformational polymorphism, respectively. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to compare their diagnostic value, as well as the sensitivity, specificity and likelihood ratio. Moreover, independent and sensitive tests from these non-invasive approaches were selected to form a parallel test that may have further improved sensitivity for diagnosis of pancreatic cancer.

Results: The AUC of serum CA199 and CA242 were 0.821 (95%CI 0.725-0.917) and 0.821 (95%CI 0.723-0.919), respectively. The optimal diagnostic value of serum CA199 for pancreatic cancer was 93 U/mL, with a sensitivity of 73.7% and specificity of 91.4%. The positive likelihood ratio of CA199 was 8.57, and the negative likelihood ratio was 0.29. The optimal diagnostic value of serum CA242 was 25 U/mL, with a sensitivity of 71.1% and specificity of 93.5%. The positive likelihood ratio of CA242 was 10.94, and the negative likelihood ratio was 0.31. The sensitivity of fecal k-ras gene mutation for diagnosis of pancreatic cancer was 77.4%, and the specificity was 81.2%. The positive and negative likelihood ratios of fecal k-ras gene mutation were 4.12 and 0.28, respectively. The sensitivity and specificity of fecal p53 gene mutation were 25.8% and 95.3%, respectively, and its positive and negative likelihood ratios were 5.49 and 0.78. The rate of fecal k-ras mutation was higher in patients with benign pancreatic diseases (57.14%) than that of controls with non-pancreatic disorders. The values of serum tumor markers and fecal k-ras and p53 gene mutation rates were not significantly different in subgroups according to site or stage of pancreatic cancer. The sensitivity and specificity of the parallel test of serum CA199 and fecal k-ras gene mutation were 94.06% and 74.22%, respectively, while the sensitivity and specificity of the parallel test of serum CA242 and fecal k-ras were 93.47% and 75.92%, respectively.

Conclusions: Serum CA199 and CA242 are valuable diagnostic tools for pancreatic cancer. The diagnostic value is further improved when they are combined with fecal k-ras gene mutation measurement.