CLAUDIN-4 IMMUNOHISTOCHEMICAL EXPRESSION IN HUMAN COLORECTAL CARCINOMA
Maha M. Atwa and Ismail F. Ismail*
Department of Pathology and *Center of Oncology and nuclear Medicine, Faculty of Medicine, Suez Canal University
Colorectal carcinoma continues to be among the most common cancers worldwide. Earlier diagnosis and better knowledge of its clinicohistological prognostic factors have contributed to the improved outcome of affected patients. Claudin-4 plays a key role in constructing the tight junction, and altered claudin-4 expression has been documented in various human malignancies; however, observed controversies in its implication were noticed and little is known about the biological significance of claudin-4 in colorectal cancers. The present study investigated the immunohistochemical expression of claudin-4 in colorectal carcinoma and its association with the different clinicopathological parameters and its prognostic significance. Twenty eight (28) colorectal carcinoma cases were included in this study. Amongst the 28 colon cancer cases examined, Claudin-4 immunopositivity was detected in 17 cases (61.3%). No statistically significant relationship was found between claudin-4 protein expression and tumor grade, tumor T stage, site, or associated bilharzial infection; however, lymph node metastasis and stage of the tumor were found to be highly statistically significant. Heterogeneous expression of claudin-4 was detected in 12 cases (70.5%) with marked positive upregulation of claudin-4 in the invasive front rather than the luminal surface. Twenty patients (85.7%) were alive while 4 (14.3%) were dead by the end of this study, and 6 patients (21.4 %) showed liver metastasis. Statistically significant relationship was found between claudin-4 immunoreactivity and liver metastasis and overall survival. The study provided evidence for an association between the expression of claudin-4, and unfavorable prognosis of colon cancer. Claudin-4 could identify a subset of colon cancer patients of high risk of colorectal cancer progression that might be benefit from adjuvant chemotherapy and/or the proposed claudin-targeted therapies in claudin-4 expressing tumors.