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Currently available colon cancer (CC) markers lack sensitivity and specificity. Kallikrein-related peptidases (KLKs) present a new class of biomarkers under investigation for diverse diseases, including cancer. KLKs are co-expressed in various tissues participating in proteolytic cascades. KLK7 in human tumours facilitates metastasis by degrading components of the extracellular matrix. KLK14 promotes tumourigenesis by activating proteinase-activated receptors. In the present study we examined the concomitant expression of KLK7 and KLK14 in245 colonic tissue specimens from 175 patients; 70 were pairs of cancerous-normal tissues, 31 were cancerous tissues and 74 were colonic adenomas. We used quantitative real-time PCR and proved that both genes are up-regulated in CC at the mRNA level. Receiver-operating characteristic (ROC) analysis of our results showed that both genes have discriminatory value between CC and adenoma tissues, with KLK14 obtaining greater distinguishing power (area under the curve [AUC]=0.708 for KLK14; AUC=0.669 for KLK7). Current work showed that the two genes are fairly co-expressed in all three types of colon tissues examined (normal rs=0.667, p<0.001, adenomas rs=0.373, p=0.001, carcinomas rs=0.478, p<0.001). KLK14 is associated with shorter disease-free survival (DFS) and overall survival (OS) of patients (p=0.003, p=0.016 respectively), whereas KLK7only with shorter DFS (p=0.004). KLK7 and KLK14 gene expression can be regarded as markers of poor prognosis for CC patients with discriminating power between CC and adenoma patients.

Aim: To evaluate the diagnostic sensitivity and accuracy and the cost-effectiveness of this technique in the detection of gastroenteropancreatic carcinoid tumors and their metastases in comparison with conventional imaging methods., Methods: Somatostatin receptor scintigraphy (SRS) was performed in 24 patients with confirmed carcinoids and 7 under investigation. The results were compared with those of conventional imaging methods (chest X-ray, upper abdominal ultrasound, chest CT, upper and lower abdominal CT). Also a cost-effectiveness analysis was performed comparing the cost in Euro of several combinations of SRS with conventional imaging modalities., Results: SRS visualized primary or metastatic sites in 71.0% of cases and 61.3% of conventional imagings. The diagnostic sensitivity of the method was higher in patients with suspected lesions (85.7% vs 57.1%). SRS was less sensitive in the detection of metastatic sites (78.9% vs 84.2%). The undetectable lesions by SRS metastatic sites were all in the liver. Between several imaging combinations, the combinations of chest X-ray/upper abdominal CT/SRS and chest CT/upper abdominal CT/SRS showed the highest sensitivity (88.75%) in terms of the number of detected lesions. The combinations of chest X-ray/upper abdominal US/SRS and chest CT/upper abdominal ultrasound /SRS yielded also a quite similar sensitivity (82%). Compared to the cost of the four sensitive combinations the combination of chest X-ray/upper abdominal ultrasound/SRS presented the lower cost, 1183.99 Euro vs 1251.75 Euro for chest CT/upper abdominal ultrasound/SRS, 1294.93 Euro for chest X/ray/upper abdominal CT/SRS and 1362.75 Euro for chest CT/upper abdominal CT/SRS., Conclusion: SRS imaging is a very sensitive method for the detection of gastroenteropancreatic carcinoids but is less sensitive than ultrasound and CT in the detection of liver metastases. Between several imaging combinations, the combination of chest X-ray/upper abdominal CT/SRS shows the highest sensitivity with a cost of 1294.93 Euro.