Evaluation of Tumor M2 Pyruvate Kinase and Endocannabinoid System Expression in Colorectal Preneoplastic and Neoplastic Lesions: Possible Use for non Invasive Diagnosis

Colorectal cancer (CRC) is a multistep process that goes through adenoma-carcinoma sequence. Many forms of CRC may be prevented by routine control, which can detect precancerous neoplasm before they undergo malignant transformation (123). For this reasons we hypothesized that a combination of simple faecal tests, may help to identify patients with higher risk of adenomas and/or CRC. The aim of this study is to clarify whether FOBT, enzyme Tumor M2-PK and endocannabinoid system molecules (CB1, CB2, FAAH), could represent diagnostic non-invasive markers, alone or in combination, for early diagnosis of CRC and its precancerous lesions. In a pivotal study we analyzed a selected population, using i-FOBT and quantitative ELISA stool test for t-M2-PK detection. i-FOBT showed the highest specificity and PPV (88.8% and 52.7% respectively); M2-PK had the best sensitivity (87.2%); the best results it obtained with combination tests; in fact if our patients had been subjected only to the i-FOBT test, 33 high risk adenoma and 14 CRC would not have been diagnosed. Supported by these findings, we analyzed a consecutive population: patients with both positive tests have only 31.6% risk of developing CRC; in contrast, patients negative to both markers, cancer risk was less than 2% (VPN 98.5%). We confirmed, also with immuoistochemistry, that increase of tumour M2-PK in patients with CRC, as well as in stool samples, is correlated with pre neoplastic stages. To investigate the expression of endocannabinoid system in CRC, CB1, CB2 and FAAH markers were studied immunochemically in different stages and normal tissue. CB receptors and their ligands, as well as FAAH inhibitions, showed to have a protective role in colorectal cancer. They, in combination with other markers (such as t-M2-PK and FOBT), could be indicated to develop a non-invasive test for an early diagnosis of cancerous and pre-cancerous colorectal lesions.