title: Cytokeratin7 and cytokeratin19 expression in high grade cervical intraepithelial neoplasm and squamous cell carcinoma and their possible association in cervical carcinogenesis.
abstract: BACKGROUND
  High risk human papillomavirus (HR HPV) infects cells at the squamocolumnar junction (SCJ) of the cervix, causing cancer. Cytokeratin (CK)7 is an SCJ marker, and stains cervical neoplasia. CK19 is a binding partner of CK7 and expressed in cervical cancer. Despite this possible association between CK7/CK19 and cervical cancer, not much is known about the mechanism of CK7/CK19 involvement in HR HPV-mediated cervical carcinogenesis.
  
  
  METHODS
  We analyzed the expression pattern of CK7, CK19, and p16 by using immunohistochemistry and HPV infection by in situ hybridization in 25 cases of high grade cervical intraepithelial neoplasia (CIN3) and in 30 cases of squamous cell carcinoma (SCC).
  
  
  RESULTS
  CK19, p16, and HPV expression was positive in all CIN3 and SCC cases. CK7 expression was positive in all CIN3 cases and in 20/30 (66%) SCCs. Each protein showed diffuse or patchy staining with topographic distinction. Patchy staining of CK7 and episomal HPV DNA overlapped in the upper layer of CIN3 and central portion of an invasive nest in the SCC, whereas patchy CK19 staining and integrated HPV DNA were usually noted in the lower layer of CIN3 and the periphery of the SCC nest. The p16 staining pattern coincided with that of CK19 in a subset of SCC.
  
  
  CONCLUSIONS
  These results suggest that CK7 may be more related with viral episomal replication and CK19 with viral integration, contributing to viral replication and malignant transformation in HR HPV infected cells. In addition, coordinate CK7/CK19 staining may be used as a valuable marker for predicting physical status of HR HPV and E7 oncoprotein level in cervical tumor.
authors.affiliation: Department of Pathology, Nowon Eulji Medical Center, Eulji University, 280-1 Hagye 1-dong, Nowon-gu, Seoul, 139-711, Korea.
authors.forename: Hojung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Pathology, Daejeon Eulji Medical Center, Eulji University, 95 Dunsanseo-ro, Seo-gu, Daejeon, 35233, Korea.
authors.forename: Hyekyung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Gachon University Gil Medical Center, 1198 Guwol-dong, Namdong-gu, Incheon, 405-760, Korea. karmacho@gmail.com.
authors.forename: Yong Kyun
authors.initials: YK
authors.lastname: Cho
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism*; D002584:Cervix Uteri / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053539:Keratin-19 / Q000378:metabolism; D053552:Keratin-7 / Q000378:metabolism; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000378:metabolism*; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000175:diagnosis / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D053539:Keratin-19; D053552:Keratin-7
keywords: CK19; CK7; Cervical cancer; HPV; Squamocolumnar junction; p16