Claudin-1 as a Biomarker of Cervical Cytology and Histology

Abstract

Several immunochemistry tests are used for triaging human papilloma virus (HPV) and cytology positive cases in cervical cancer screening and as an adjunct test to diagnose cervical cancer. Claudin-1 (CLDN1) protein is a major component of the tight junction, shown to have altered expression in cervical cancer. In this study, value of CLDN1 was analysed as a screening and triage immunochemistry test compared to cytology and HPV testing. A population of 352 women attending colposcopic referral visits resulting in cervical conisation and a second population of 150 women attending routine gynaecological visits with negative cervical cytology were enrolled in a multi-centre clinical study in Hungary. Cytology and HPV (Genoid Full Spectrum HPVAmplification and Detection System) testing were carried out along with immunocytochemistry for CLDN1, and as a reference, using CINtec p16 Cytology Kit. Three different evaluation protocols were used which assessed immunostaining characteristics with or without cytological readings. High correlation observable between p16INK4a and CLDN1 established CLDN1 as a competing marker in cervical cancer. Concordance of CLDN1 immunostaining of cervical intraepithelial neoplasia 2 and above (CIN2+) positives was 84.0 % (73.8–89.3); concordance of CIN2+ negatives was 69.0 % (59.6–75.8). In conclusion, CLDN1 has similar diagnostic potential as p16INK4a, our results established it as a histological and cytological biomarker with the potential to improve the clinical performance of cervical cytology and histology.

Claudin-1 expression in cervical cancer

“…Dysregulation of claudin-1 has previously been demonstrated to be involved in tumorigenesis and progression in various malignant entities, including cervical cancer (2,5). The pivotal role of claudin-1 in tumorigenesis has been hypothesized in the context of the pre-cancerous (8). However, the findings of the current study did not determine any significant association between the claudin-1 expression levels in the cervical cancer patient cohort and the tumor size, FIGO stage or grade.…”

“…INK4a and claudin-1 expression in pre-invasive cervical lesions (8). Consequently claudin-1 could serve as a marker for pre-invasive lesions and early invasive cervical carcinoma.…”

“…In vitro studies have demonstrated that claudin-1 is involved in the tumorigenesis of cervical cancer (3,6,7). In cervical intraepithelial neoplasia, claudin-1 expression levels correlate with p16 INK4a , increasing with the severity of cervical dysplasia (8 Histochemical analysis. Details of the histopathological diagnosis, FIGO stage, patient characteristics and adjuvant therapies were retrieved from hospital records, along with follow-up data.…”

Immunocytochemistry for Claudin‐18 and Maspin in biliary brushing cytology increases the accuracy of diagnosing pancreatobiliary malignancies

“…Claudin‐4 was reported positive in 97% of effusion samples from patients with ovarian, lung and endometrial carcinomas, and in one patient with pancreatic carcinoma, with these carcinoma cells showing strong and diffuse immunopositivity . Claudin‐1 expression was observed as linear membrane positivity on cervical smear samples . In our study, Claudin‐18 was distributed along the entire cell membrane of most adenocarcinoma cells but was almost completely absent from non‐neoplastic epithelial cells.…”

“…Claudin‐18 is detected in gastrointestinal and lung tissues and was shown to be overexpressed immunohistochemically in pancreatic and biliary duct adenocarcinomas. Although few studies reported that Claudin‐4 or Claudin‐1 expression was present in the effusion or cervical samples, to our knowledge no study has evaluated Claudin‐18 expression on alcohol‐fixed cytology smears.…”