Zaccaro Cristina, Saracino Ilaria Maria, Fiorini Giulia, Figura Natale, Holton John, Castelli Valentina, Pesci Valeria, Gatta Luigi, Vaira Dino
Department of Medical and Surgical Sciences, University of Bologna, S. Orsola Hospital via Massarenti, 9, 40138, Bologna, Italy.
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
Intern Emerg Med. 2017 Apr;12(3):333-339. doi: 10.1007/s11739-017-1610-3. Epub 2017 Feb 2.
Colorectal cancer (CRC) is a multistep process that involves adenoma-carcinoma sequence. CRC can be prevented by routine screening, which can detect precancerous lesions. The aim of this study is to clarify whether faecal occult blood test (i-FOBT), tumor M2 pyruvate kinase (t-M2-PK), and endocannabinoid system molecules (cannabinoid receptors type 1-CB1, type 2-CB2, and fatty acid amide hydrolase-FAAH) might represent better diagnostic tools, alone or in combination, for an early diagnosis of CRC. An immunochemical FOB test (i-FOBT) and quantitative ELISA stool test for t-M2-PK were performed in 127 consecutive patients during a 12 month period. Endocannabinoid system molecules and t-M2-PK expression were detected by immunostaining in healthy tissues and normal mucosa surrounding adenomatous and cancerous colon lesions. i-FOBT and t-M2-PK combination leads to a better diagnostic accuracy for pre-neoplastic and neoplastic colon lesions. T-M2-PK quantification in stool samples and in biopsy samples (immunostaining) correlates with tumourigenesis stages. CB1 and CB2 are well expressed in healthy tissues, and their expression decreases in the presence of advanced stages of carcinogenesis and disappears in CRC. FAAH signal is well expressed in normal mucosa and low-risk adenoma, and increased in high-risk adenoma and carcinoma adjacent tissues. This study shows that high levels of t-M2-PK in addition to FOBT enhance the power of a CRC screening test. Endocannabinoid system molecule expression correlates with colon carcinogenesis stages. Developing future faecal tests for their quantification must be undertaken to obtain a more accurate early non-invasive diagnosis for CRC.
结直肠癌（CRC）是一个涉及腺瘤-癌序列的多步骤过程。CRC可通过常规筛查预防，常规筛查能检测出癌前病变。本研究的目的是阐明粪便潜血试验（i-FOBT）、肿瘤M2丙酮酸激酶（t-M2-PK）和内源性大麻素系统分子（1型大麻素受体-CB1、2型大麻素受体-CB2和脂肪酸酰胺水解酶-FAAH）单独或联合使用时，是否可能成为CRC早期诊断的更好诊断工具。在12个月期间，对127例连续患者进行了免疫化学FOB试验（i-FOBT）和t-M2-PK的定量ELISA粪便检测。通过免疫染色检测健康组织以及腺瘤性和癌性结肠病变周围正常黏膜中的内源性大麻素系统分子和t-M2-PK表达。i-FOBT和t-M2-PK联合使用可提高对肿瘤前和肿瘤性结肠病变的诊断准确性。粪便样本和活检样本（免疫染色）中的t-M2-PK定量与肿瘤发生阶段相关。CB1和CB2在健康组织中表达良好，在致癌作用晚期时其表达降低，在CRC中消失。FAAH信号在正常黏膜和低风险腺瘤中表达良好，在高风险腺瘤和癌旁组织中增加。本研究表明，除FOBT外，高水平的t-M2-PK可增强CRC筛查试验的效能。内源性大麻素系统分子表达与结肠癌发生阶段相关。必须开展未来粪便检测以对其进行定量，从而获得更准确的CRC早期非侵入性诊断。
