title: Enhanced expression of hedgehog signaling molecules in squamous cell carcinoma of uterine cervix and its precursor lesions.
abstract: The hedgehog (Hh)-signaling pathway plays an essential role in normal development. Deregulation of this pathway is responsible for several types of cancers. The aim of this study was to determine the expression pattern and the extent of Hh-signaling molecules in squamous cell carcinoma of uterine cervix and its precursor lesions. A total of 106 uterine cervical cancers and related lesions (37 squamous cell carcinomas, 23 cervical intraepithelial neoplasia (CIN) III, 10 CIN II, four CIN I, 32 normal cervical epithelia) were immunohistochemically analyzed with anti-Shh, Indian Hh (Ihh), Patched (PTCH), Smoothened (Smo), Gli-1, Gli-2, Gli-3 antibodies on paraffin blocks. The results showed that the expression of all the Hh-signaling molecules was greatly enhanced in uterine cervical tumors, including carcinoma and its precursor lesions. The staining pattern was mainly cytoplasmic except for Gli-1/2, whose expression was observed in both cytoplasm and nucleus. In case of Ihh, PTCH, Smo and Gli-1, their expression in normal epithelium was completely absent or rare. The expression of all the seven Hh-signaling molecules mentioned above was significantly increased in CIN II/III and carcinoma, compared with that in normal epithelium (P < 0.05). The expression of Shh was increased by double; the first increase occurred in normal epithelium-CIN transition, and the second, during the progression of CIN to carcinoma. These results strongly suggest that the Hh-signaling pathways were extensively activated in carcinoma and CIN of uterine cervix. In conclusion, the Hh-signaling pathways may be involved in carcinogenesis of squamous cell carcinoma of uterine cervix and can be considered as a potential therapeutic target.
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Yan Hua
authors.initials: YH
authors.lastname: Xuan
authors.forename: Hun Soon
authors.initials: HS
authors.lastname: Jung
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shin
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Wun Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: You Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Seok-Hyung
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D053823:Hedgehog Proteins; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; C509239:SHH protein, human; D015534:Trans-Activators