Increased claudin-1 protein expression in hepatic metastatic lesions of colorectal cancer.

BACKGROUND: The molecular and morphological alterations of the tight junctions in hepatic metastatic lesions are poorly understood. The possible involvement of claudin-1 (CL-1), which is one of the major tight junctional proteins, was investigated in the tumorigenesis of hepatic metastasis in patients with colorectal cancer (CRC). PATIENTS AND METHODS: A total of 14 patients with hepatic metastasis of CRC who underwent surgical treatment from January 2007 until December 2010 at the Kurume University Hospital in Fukuoka, were examined. CRC tissue specimens were analyzed to determine whether the levels of CL-1 correlated with clinicopathological factors and to determine the roles of CL-1, ß-catenin, and E-cadherin in the alterations of the tight junctions during tumorigenesis. RESULTS: In seven cases, the tumors were located in the colon, while the other seven tumors were found in the rectum. There were eight cases of synchronous liver metastasis, while there were six cases of metachronous liver metastasis. The levels of the CL-1 protein were up-regulated in CRC and in hepatic metastatic lesions. The levels of ß-catenin were positive or up-regulated in the primary CRC lesions and in hepatic metastatic lesions. Despite the finding that the levels of E-cadherin were decreased in CRC, they were clearly up-regulated in hepatic metastatic lesions in this study. CONCLUSION: This study demonstrated that CL-1 levels were up-regulated in liver metastatic lesions from primary CRC lesions. Moreover, the levels of E-cadherin were increased in liver metastatic lesions, which may point to the existence of interactions between CL-1 and E-cadherin in hepatic metastatic lesions. These observations suggest that CL-1 plays a pivotal role in the regulation of cellular morphology and in the behavior of metastatic processes in CRC.

Relationship between ulcerative colitis patients treated with leukocytapheresis and ulcerative colitis-associated colorectal cancer.

BACKGROUND: Leukocytapheresis (LCAP) is a recent modality for treatment of patients with ulcerative colitis (UC). This study aimed to assess whether LCAP changed the development of colorectal cancer (CRC) in patients with UC. PATIENTS AND METHODS: A total of 42 patients with UC underwent surgical treatment from January 2001 until October 2010 at Kurume University Hospital. The patient details, preoperative therapy, operative indication and complications were obtained from our prospective database. Univariate, multivariate analysis and tree model were used for statistical analysis. RESULTS: In patients who received LCAP before surgery, CRC was significantly less frequent (p=0.0321). CRC incidence following LCAP increased when the disease period from diagnosis of UC exceeded 133 months. Multivariate analysis showed that the odds for undergoing LCAP were significantly higher (p=0.0305) in those cases with a total dose of steroid more than 2.57 g. CONCLUSION: LCAP may suppress CRC in UC patients.

Increased claudin-1 protein expression contributes to tumorigenesis in ulcerative colitis-associated colorectal cancer.

BACKGROUND: The molecular and morphological alterations of the tight junctions in ulcerative colitis (UC)-associated colorectal cancer are still poorly understood. The possible involvement of claudin-1 (CL-1), one of the major tight junctional proteins, was investigated in the tumorigenesis of UC-associated CRC. PATIENTS AND METHODS: A total of 39 patients with UC underwent surgical treatment from January 2001 until October 2009 at Kurume University Hospital in Fukuoka. CRC tissue specimens were analyzed to determine whether the expression of CL-1 correlates with clinicopathological factors and to determine the role of CL-1 and ß-catenin in the alteration of tight junctions during tumorigenesis. RESULTS: The operations were 30 of elective surgery and 9 of emergency surgery. Colectomy was performed in five patients (12.8%) because of UC-associated CRC, and in another patient (2.6 %) because of high-grade dysplasia. The immunostaining pattern of the high-grade dysplasia and UC-associated CRC for CL-1 showed much stronger and more diffuse staining in comparison to the normal or UC colonic mucosa. The expression of ß-catenin was also positive or up-regulated in all of the UC-associated CRC and high-grade dysplasia tissue specimens. CONCLUSION: These observations suggested that CL-1 plays a pivotal role in the regulation of cellular morphology and behavior in UC. We speculate that increased CL-1 expression may be involved in the early stages of transformation in UC-associated neoplasia. CL-1 protein may therefore be a good candidate for surveillance of patients with UC.