Abstract

Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in non-melanoma skin carcinomas. A series of 26 primary cutaneous skin lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle Upon Tyne, England, UK) was scored by an average of the mean labeling intensity (MLI), where no nuclear staining = 0, weak nuclear staining = 1, moderate nuclear staining = 2, and strong nuclear staining = 3. All basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC) cases exhibited negative nuclear staining, for an average MLI of 0. Keratoacanthomas, squamous cell carcinoma in situ (SIS), and well-differentiated squamous cell carcinomas (SCCs) exhibited negative to weak nuclear staining, for an average MLI of 0.4 +/- 0.3. Moderately differentiated SCCs exhibited moderate nuclear staining, for an average MLI of 1.8 +/- 0.6. Poorly differentiated SCCs and metastatic SCCs exhibited very strong nuclear staining, with an average MLI of 2.8 +/- 0.2. Ets-1 is not expressed in cutaneous BCC or MCC and is weakly expressed in SIS and forms of well-differentiated SCC. Although the intensity of Ets-1 immunostaining distinguished between well-differentiated and poorly differentiated SCC (p < 0.0001), it failed to discriminate between in situ and well-differentiated SCCs. The preliminary data suggests Ets-1 may be important in the pathogenesis of invasive SCC.

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