title: Evaluation of the 'Hedgehog' signaling pathways in squamous and basal cell carcinomas of the eyelids and conjunctiva.
abstract: The purpose of the present study was to assess the role of hedgehog signaling pathway in the carcinogenesis of eyelid skin and conjunctival epithelial malignant tumors. The study was conducted on specimens from 41 patients with cutaneous eyelid basal cell carcinoma, 22 with bulbar conjunctival squamous cell carcinoma, 12 with bulbar conjunctival intraepithelial neoplasia. Major molecules of Hedgehog signaling pathway (Sonic Hedgehog [Shh] and Patched-1 [Ptch-1] and Glioma-associated oncogene [Gli-1]) were evaluated in paraffin-embedded tissue specimens using immunohistochemical staining. For each specimen, the percentage (<10%, 10-50%, >50%) and the intensity of the immunohistochemical staining (graded from 0 to 3) were calculated and the scores obtained by multiplication of two values were analyzed using the Kruskall-Wallis test. Shh and Ptch-1 expression levels were statistically significantly lower in the basal cell carcinoma group compared with the squamous cell carcinoma group (P=0.043 for Shh; P=0.030 for Ptch-1). In the conjunctival squamous cell carcinoma group, the Ptch-1 score was 0 in ~25% of specimens and the Gli-1 score was ≤2 in ~45% of cases. In the conjunctival intraepithelial neoplasia group, the Ptch-1 score was ≥2 in 66% of specimens, the Gli-1 score was ≤2 in ~92% of cases. Ptch-1 mutations contribute to the development of cutaneous eyelid basal cell carcinoma. The present study provides evidence that alterations in hedgehog signaling pathways may lead to transformation of the conjunctival intraepithelial neoplasia into invasive squamous cell carcinoma.
authors.affiliation: Department of Ophthalmology, Acibadem University School of Medicine, 34303 Istanbul, Turkey.
authors.forename: Ali Riza Cenk
authors.initials: AR
authors.lastname: Celebi
authors.affiliation: Department of Ophthalmology, Hacettepe University School of Medicine, 06100 Ankara, Turkey.
authors.forename: Hayyam
authors.initials: H
authors.lastname: Kiratli
authors.affiliation: Department of Pathology, Hacettepe University School of Medicine, 06100 Ankara, Turkey.
authors.forename: Figen
authors.initials: F
authors.lastname: Soylemezoglu
keywords: conjunctival intraepithelial neoplasia; glioma-associated oncogene-1 protein; patched-1 protein; periocular skin cancers; sonic hedgehog protein