The Prognostic Role of Claudins in Head and Neck Squamous Cell Carcinomas

Abstract

The expression of tight junction proteins is frequently altered in epithelial cancers. The loss of cell-cell adhesion associates with enhanced metastatic potential, which underlies the role of altered expression pattern of tight junction component claudins (CLDNs). Our study assessed the expression of CLDN 1, 2, 3, 4, 7, 8 and 10 in squamous cell carcinoma of the head and neck region (HNSCC) including oropahrynx, larynx, and hypopharynx in comparison to normal epithelial tissue of the same patient. The surgical samples were examined by tissue microarray and immunohistochemistry, the expression was calculated by H-score, which took account of intensity and percentage of positivity as well. Both normal and cancerous tissue proved negative for CLDN 3, 8 and 10. Normal epithelia showed mild expression of CLDN 4, but the minimal positivity disappeared in squamous cancer. In case of CLDN 1 and CLDN 7 we demonstrated significantly increased intensity in cancer, while CLDN 2 showed decreased expression compared with normal epithelium. The normal polarity and distribution of claudins were lost in HNSCC. Moreover, preserved expression of CLDN 2 (but not that of 1 and 7) was associated with better survival, which suggested a potential prognostic role of CLDN 2.

Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17 cytokines in adults with atopic dermatitis

“…We also explored the expression of an additional TJ protein (CLDN‐4) in AD individuals. CLDN‐4 has been associated with coeliac disease, gluten sensitivity, head and neck carcinomas and infectious diseases, but there was no significant decreased expression in AD individuals …”

“…CLDN-4 has been associated with coeliac disease, gluten sensitivity, head and neck carcinomas and infectious diseases, but there was no significant decreased expression in AD individuals. 15,16 Even though the majority of patients with AD and FLG mutations outgrow their AD, there are individuals with severe AD who do not have FLG null mutations, and the opposite situation applies. This suggests that a number of additional factors are involved in the development of AD, including other gene mutations and exposure to allergens and microbes.…”

Claudin-1, A Double-Edged Sword in Cancer

“…Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent tumor worldwide [112]. Tissue microarray and immunohistochemistry assays of surgical samples suggested that CLDN-1 expression is increased in squamous cell cancer [46,113]. It has been shown previously that CLDN-1 induces the generation of tumor lymphatic vessels and increases the lymph node metastasis [47].…”

The Expression of CLDN6 in Hepatocellular Carcinoma Tissue and the Effects of CLDN6 on Biological Phenotypes of Hepatocellular Carcinoma Cells

“…CLDN6, one of 28 members of the CLDNs family 15 , was first found and confirmed as a breast cancer suppressor gene. Overexpression of CLDN6 can inhibit the proliferation, migration and invasion of breast cancer cells 16 .…”