Background: Certain epidermal appendage tumors, includinghyperplasias (hamartomas), adenomas, benign epitheliomas,primordial epitheliomas, and malignant tumors, canexhibit any stage of differentiation. Several moleculesassociated with tumorigenesis, such as Gli-1, pleckstrinhomology-like domain, family A, member 1 (PHLDA-1),transforming growth factor (TGF)-β1, TGF-β2, and p63, areassociated with tumor grade and aggressive behavior infollicular and sebaceous tumors in ways that are not wellunderstood. Objective: The aim of this study was to elucidatethe expression of Gli-1, PHLDA-1, TGF-β1/β2, and p63 inbenign and malignant tumors of the hair and sebaceousglands and to determine their importance in the degree oftumor differentiation. Methods: Immunohistochemistry wasperformed in follicular and sebaceous tumors using antibodiesagainst Gli-1 (sebaceous tumor marker), PHLDA-1(hair follicle outer root sheath [ORS] cell marker), p63, TGF-β1, and TGF-β2. Results: Gli-1 was expressed in basaloidcells, sebocytes, and sebaceous carcinoma cells, andexpression levels decreased as differentiation progressed.
PHLDA-1 was expressed in ORS cells and some folliculartumor cells. Expression of p63 was observed in the nuclei ofthe outermost basaloid cells (seboblasts), poorly differentiatedsebaceous carcinoma cells, and tumor cells toward thedirection of the hair. Remarkably, TGF-β1 was expressedexclusively in the nuclei of benign and malignant follicular(hair) tumors, but not in sebaceous tumors, at levels thatcorrelated with the degree of differentiation. Conclusion:We propose that p63 and/or TGF-β1 are useful forpredicting the degree of differentiation and malignantpotential of sebaceous and follicular tumors and for distinguishingtrichilemmal carcinoma from sebaceous carcinoma.