Abstract
Claudins are the main sealing protein of the intercellular tight junctions and play an important role in cancer progression and dissemination. Several authors have reported conflicting results of claudin-1 expression in colorectal carcinoma. The goal of this study is to examine claudin-1 expression in a tissue microarray of colorectal cancer and metastases, simultaneously, in order to assess the prognostic value of this protein in colorectal cancer. This study analysed the expression of claudin-1 by immunohistochemistry in 99 tissue samples (including 33 colorectal cancer cases with 33 concordant lymph node metastases and 33 concordant cancer-adjacent normal tissues, all from the same patients). The tumours included adenocarcinomas from the colon (n=25) and from the rectum (n=8). This is the first study to demonstrate the expression of claudin-1 protein across a sample of colorectal cancer and its metastases, simultaneously. We report loss of claudin-1 expression in the lymph node metastases in the majority of cases. We also report differential expression of claudin-1 among colorectal cancers of different grades, with the highest expression being in well-differentiated, low-grade tumours; and complete loss of expression in the majority of cases of poorly-differentiated, high grade tumours.
Highlights
Claudins are tight junction proteins which, along with adherens junctions and desmosomes form cellular sheets
The IHC stain result was not reported in one of the lymph node metastasis of a colorectal carcinoma (D-2) and in a cancer adjacent normal appearing tissue of a rectal carcinoma (J-3), because tissues were missing in both cases
Claudin-1 expression was primarily membranous in the majority of well-differentiated colorectal carcinoma (CRC) cases of our study (Figure 1A), faint to strong cytoplasmic and nuclear staining were seen in some of these cases (Figure 1B)
Summary
Claudins are tight junction proteins which, along with adherens junctions and desmosomes form cellular sheets. Tight junctions (TJs) are critical for sealing of cellular sheets, thereby controlling paracellular ion flux. Tight junctions play critical roles in maintaining cell polarity and signal transductions [1,2]. Claudins are the backbone of tight junction strands, and are essential components to the function of tight junctions [1]. The high degree of cellular organization typically observed in normally differentiated tissues is often lost in cancer. Loss of epithelial integrity with changing claudins’ levels and resultant increased paracellular leakage plays a critical role in providing a space for tumor cell mobility and increased nutrients’ supply for tumor cells underneath
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