HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Expression profile of tight junction protein claudin 3 and claudin 4 in ovarian serous adenocarcinoma with prognostic correlation

Y.-L. Choi1, J. Kim1, M.J. Kwon2, J.-S. Choi3, T.-J. Kim4, D.-S. Bae4, S.S. Koh5, Y.-H. In6, Y.W. Park7, S.H. Kim8, G. Ahn1 and Y.K. Shin2

1Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, 2Laboratory of Molecular Pathology, Department of Pharmacy, Seoul National University College of Pharmacy, Seoul, Korea, 3Department of Pathology, Cheil General Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea and 4Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, 5LG Life Sciences, Ltd., R&D Research Park, Daejeon, Korea, 6BIT center, CT&D Ltd., Seoul, Korea, 7Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea and 8Department of Pathology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, Korea

Offprint requests to: Young Kee Shin, M.D., Ph.D., Laboratory of Molecular Pathology, Department of Pharmacy, Seoul National University College of Pharmacy, San 56-1, Sillim-dong, Gwanak-gu, Seoul, 151-742, Korea. e-mail: ykeeshin@snu.ac.kr


Summary. Tight junction proteins claudin 3 (CLDN3) and claudin 4 (CLDN4) are frequently altered in several human cancers, including ovarian carcinomas. Here, we examined the gene expression of CLDN3 and CLDN4 in various tumors, including 19 normal ovaries and 47 ovarian carcinomas by analyzing Affymetrix HG-U133 array data. Furthermore, a total of 114 ovarian serous tumors, including 10 adenomas, 20 borderline tumors and 84 carcinomas, were analyzed immunohistochemically to confirm the expression of two proteins and we assessed the association of their expression with the clinicopathological characteristics and survival of the patients. The microarray experiment revealed CLDN3 and CLDN4 transcripts were significantly up-regulated by 5-fold or more in most subtypes of ovarian epithelial carcinomas while the immunohistochemical analyses indicated that each protein was expressed in 68 (81.0%) and 72 (85.7%) of 84 serous adenocarcinomas, respectively. Borderline serous tumors and adenomas showed significantly lower expression of these proteins than the adenocarcinomas. Kaplan-Meier survival analysis showed that serous adenocarcinoma patients with high CLDN3 expression had substantially shorter survival (P=0.027). Multivariate analysis demonstrated that CLDN3 overexpression is an independent negative prognostic factor. Our findings suggest that CLDN3 overexpression can be used as a prognostic indicator in ovarian serous carcinomas. Moreover, CLDN3 may be a promising target for antibody-based therapy of ovarian carcinomas. Histol Histopathol 22, 1185-1195 (2007)

Key words: Ovarian serous tumor, Tight junction, Claudin 3, Claudin 4

DOI: 10.14670/HH-22.1185