Expression Patterns of Gli-1, Pleckstrin Homology-Like Domain, Family A, Member 1, Transforming Growth Factor-β1/β2, and p63 in Sebaceous and Follicular Tumors

Abstract

BackgroundCertain epidermal appendage tumors, including hyperplasias (hamartomas), adenomas, benign epitheliomas, primordial epitheliomas, and malignant tumors, can exhibit any stage of differentiation. Several molecules associated with tumorigenesis, such as Gli-1, pleckstrin homology-like domain, family A, member 1 (PHLDA-1), transforming growth factor (TGF)-β1, TGF-β2, and p63, are associated with tumor grade and aggressive behavior in follicular and sebaceous tumors in ways that are not well understood.ObjectiveThe aim of this study was to elucidate the expression of Gli-1, PHLDA-1, TGF-β1/β2, and p63 in benign and malignant tumors of the hair and sebaceous glands and to determine their importance in the degree of tumor differentiation.MethodsImmunohistochemistry was performed in follicular and sebaceous tumors using antibodies against Gli-1 (sebaceous tumor marker), PHLDA-1 (hair follicle outer root sheath [ORS] cell marker), p63, TGF-β1, and TGF-β2.ResultsGli-1 was expressed in basaloid cells, sebocytes, and sebaceous carcinoma cells, and expression levels decreased as differentiation progressed. PHLDA-1 was expressed in ORS cells and some follicular tumor cells. Expression of p63 was observed in the nuclei of the outermost basaloid cells (seboblasts), poorly differentiated sebaceous carcinoma cells, and tumor cells toward the direction of the hair. Remarkably, TGF-β1 was expressed exclusively in the nuclei of benign and malignant follicular (hair) tumors, but not in sebaceous tumors, at levels that correlated with the degree of differentiation.ConclusionWe propose that p63 and/or TGF-β1 are useful for predicting the degree of differentiation and malignant potential of sebaceous and follicular tumors and for distinguishing trichilemmal carcinoma from sebaceous carcinoma.

Glioma-Associated Oncogene-1 Expression in Basal Cell Carcinoma and Its Histologic Mimics

“…However, another study identified Gli-1 expression in 5 of 5 cases, with 4 cases demonstrating moderate staining intensity. 11 The results of the current study deviate somewhat from prior findings, as only 4 of 11 cases show expression of Gli-1, all with weak (1+) staining intensity. These findings suggest that Gli-1 may be useful in differentiating sebaceous carcinoma from BCC because of both the lower rate of positivity and the weaker expression seen with sebaceous carcinoma.…”

“…Further evaluating these tumor types in larger numbers may provide additional insight into whether significant differences exist in their expression of Gli-1 compared with BCC, and confirm the differences that have been identified in this study compared with the prior. [10][11][12] Overall, although Gli-1 may not distinguish between tumors with differentiation toward the basal layer of the epithelium, it may play a role in separating that group of tumors from tumors with adnexal differentiation. The presence of weak cytoplasmic staining only should raise the possibility of sebaceous carcinoma, whereas the presence of any cytoplasmic staining appears to eliminate the diagnosis of Merkel cell carcinoma from consideration.…”

Sebaceous adenocarcinomas of the major salivary glands: a clinicopathological analysis of 10 cases

“…Regarding p63, this marker has been suggested to be useful to differentiate muco‐epidermoid carcinoma from sebaceous adenocarcinoma; p63 was negative in the latter and expressed in muco‐epidermoid carcinomas, particularly in the epidermoid component . However, p63 expression has been associated with the degree of tumour differentiation in sebaceous carcinoma of the skin, as it was expressed in immature sebocytes as well as in poorly differentiated carcinoma cells . Interestingly, five of the studied cases were positive for p63, which was expressed mainly in the most peripheral or basal layers of the tumour nests, when it is expected to be located in the less differentiated cells (see Figure B).…”

The expression patterns and prognostic significance of pleckstrin homology-like domain family A (PHLDA) in lung cancer and malignant mesothelioma

“…P53 density was also higher in LUAD when compared with MM. Increasing evidence demonstrates that PHLDA protein levels, based on immunohistochemistry, were associated with diagnosis, prognosis, and targeted therapy in different cancer cells (31)(32)(33)(34)(35), including lung cancer (8).…”