Increased expression of claudins in cervical squamous intraepithelial neoplasia and invasive carcinoma

Claudins (CLDNs), of which 24 types have been identified, are integral transmembrane proteins of the tight junctions that are critical for maintaining cell adhesion and polarity. They also act as selective barriers. Cells and tissues are characterized by individual CLDN patterns; the composition and levels of expression change during differentiation and tumor formation. Alterations in the expression of individual CLDNs have been detected in several carcinomas and shown to be related to progression and invasion; however, their role in carcinogenesis is controversial. Using a panel of polyclonal (CLDNs 1, 3, and 7) and monoclonal (CLDNs 2 and 4) antibodies, CLDN pattern and expression were studied by immunohistochemistry in 105 cervical tissue specimens, including normal epithelia (n = 20), cervical intraepithelial neoplasias (CINs; CIN 1/2, n = 27; CIN 3, n = 10), carcinoma in situ (CIS, n = 15), and 33 squamous keratinizing and nonkeratinizing invasive carcinomas. No CLDN 3 was observed in normal or intraepithelial neoplastic cells, but significantly increased expression of CLDNs 1, 2, 4, and 7 was detected in the CIN/CIS lesions and invasive carcinomas compared with the normal tissues (P < .001) and reduced reactivity of CLDNs 1 and 2 was observed in invasive cervical cancers compared with CIN 3/CIS (P = .0001) and of CLDNs 2, 4, and 7 compared with CIN 1/2. These results indicate increased expression of CLDNs in the early phase of carcinogenesis in intraepithelial lesions, which decreases during progression to invasive disease. Expression of CLDN 1 was strongest in premalignant stages; thus, it may serve as a good diagnostic marker for the detection of CIN.