Detection of Claudin-1 in tumors of the colon

Konference: 2010 6. sympózium a workshop molekulární patologie a histo-cyto-chemie

Kategorie: Onkologická diagnostika

Téma: Postery

Číslo abstraktu: p003

Autoři: Doc. MUDr. Svetlana Brychtová, Ph.D.; Mgr. Michala Bezděková, Ph.D.; Mgr. Eva Sedláková

Introduction: The hallmark of cancer cell invasion is disruption of cell-cell junction leading to changes in the expression of junctional proteins. The role of the adherens junction (AJ) proteins has been studied extensively, but the role of tight junction (TJ) proteins has not been clearly defined. TJs form a network of anastomosing strands within the cell membranes, serving as an important barrier in epithelial and endothelial cells against the paracellular passage of macromolecules and to separate the plasma membrane into apical and basolateral domains. TJ proteins are believed to be critical in the neoplastic process via their roles as couplers of the extracellular compartment to intracellular signalling pathways and the cytoskeleton. Alteration of TJ proteins may also allow increased diffusion of nutrients and growth factors critical for tumor growth and survival. In addition, loss of TJ integrity is important for the development of the metastatic phenotype.

Claudins are a family of proteins integral to the structure and function of TJ and their altered expression has been detected in several types of cancer.

Aim: The aim of the study was to determine the role of Claudin-1 expression in carcinomas and adenomas of the colon.

Material and Methods: Altogether 40 cases including adenocarcinomas and adenomas with various degrees of dysplasia were analyzed by indirect immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections using mouse monoclonal anti-Claudin-1 primary antibody, sc-81796 diluted 1:500 (Santa Cruz Biotechnology, INC.). Protein detection was performed in the staining automaton Ventana Benchmark. Evaluation was done by H-score (percent of positive cell x intensity of staining).

Results: In normal colonic mucosa, Claudin-1 showed only weak membranous staining. Marked increase of Claudin-1 expression was detected in adenomas, even in those without any dysplastic changes. Similarly, adenocarcinomas overexpressed the protein, and the differences between adenomas and carcinomas were not significant. However, we demonstrated different protein location. Claudin-1 remained located in cytoplasmic membranes in adenomas without or with mild degree of dysplasia, whereas the shift to the cytoplasma with only cytoplasmic or membranous/cytoplasmic expression was observed in severe dysplasias and in carcinomas.

Increased expression of Claudin-1 was observed in histologically normal mucosa close to the neoplastic areas, when compared to distant areas.

Conclusion: We demonstrated that Claudin-1 deregulation is involved in early stage of colon cancerogenesis and itsubstantially may contribute to the neoplastic transformation.

This work was supported by grants GACR P304/10/1070 and MSM 6198959216.

Datum přednesení příspěvku: 23. 4. 2010