Evaluation of the ‘Hedgehog’ signaling pathways in squamous and basal cell carcinomas of the eyelids and conjunctiva

Celebi,Ali  Riza Cenk; Kiratli,Hayyam; Soylemezoglu,Figen

doi:10.3892/ol.2016.4625

Evaluation of the ‘Hedgehog’ signaling pathways in squamous and basal cell carcinomas of the eyelids and conjunctiva

Authors:
- Ali Riza Cenk Celebi
- Hayyam Kiratli
- Figen Soylemezoglu
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Affiliations: Department of Ophthalmology, Acibadem University School of Medicine, 34303 Istanbul, Turkey, Department of Ophthalmology, Hacettepe University School of Medicine, 06100 Ankara, Turkey, Department of Pathology, Hacettepe University School of Medicine, 06100 Ankara, Turkey
Published online on: May 25, 2016 https://doi.org/10.3892/ol.2016.4625
Pages: 467-472
Copyright: © Celebi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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