Expression of Shh and Wnt signaling pathway proteins in eyelid sebaceous gland carcinoma: clinicopathologic study.

PURPOSE

Activation or dysregulation of the Sonic hedgehog (Shh) and Wnt signaling pathways is suggested to lead to the development of many human malignancies. In this study, we investigated Shh and Wnt signaling protein expression in eyelid sebaceous gland carcinoma, and analyzed their correlation with clinical characteristics of the tumor.

METHODS

Patients who underwent surgical resection of eyelid sebaceous gland carcinoma from 1999 to 2011 were recruited for the study. Immunohistochemical stainings of Shh signaling proteins (Shh, Gli-1, Gli-2, Gli-3, and ABCG2) and Wnt signaling proteins (Wnt, glycogen synthase kinase 3β, β-catenin, lipoprotein receptor-related protein [LRP], and c-Myc) were conducted.

RESULTS

Thirty-seven cases of eyelid sebaceous gland carcinoma were included in this study. Twenty-nine patients showed no metastasis, and eight patients showed lymph node or distant metastasis. Shh, ABCG2, and Wnt proteins were more highly expressed in the group with metastasis than in the group without metastasis (P = 0.031, P = 0.015, and P = 0.001, respectively; χ(2) test). Patients showing high ABCG2 expression, Wnt, or LRP expression developed metastasis more commonly than those with low ABCG2, or without Wnt or LRP expression (log rank test, P = 0.019, 0.001, and 0.000, respectively).

CONCLUSIONS

The group with metastasis showed higher expression levels of Shh, ABCG2, and Wnt than did the group without metastasis, and patients with strong ABCG2 expression, Wnt, or LRP expression showed higher cumulative incidence of lymph node or distant metastasis, implying that activation of the Shh and Wnt signaling pathway is associated with aggressive behavior of the tumor.