Abstract:

SMAD4 belongs to the Darfwin family of proteins. It is an intracellular mediator of TGF-beta family and activin type 1 receptor. It mediates TGF-beta signaling to regulate transcription of target genes i.e. cell growth and differentiation. Mutations in SMAD4 gene and subsequently loss of its immunohistochemical expression is found in majority of pancreatic carcinomas as well as approximately 15% of colorectal carcinomas and occasionally (less than 10%) in the rest of human cancers. In this study, we evaluated SMAD4 expression in 17 benign and 33 malignant tumors of the cutaneous eccrine apparatus, based on the physiological similarities between abovementioned and exocrine pancreatic glands. We found cytoplasmic SMAD4 expression in all benign cases where only one case had complete SMAD4 loss. In malignant tumor group, 55% of cases showed nuclear SMAD4 expression with the rest having strictly cytoplasmic pattern of the stain. In the cytoplasmic group, we found focal SMAD4 loss in 5 cases with only one case having complete SMAD4 loss. SMAD4 expression has never been evaluated in cutaneous eccrine neoplasias. Our findings might indicate the involvement of SMAD4 pathway in malignant eccrine tumors as well as have a potential diagnostic utility.

Financial Disclosure:
No current or relevant financial relationships exist.

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Tatsiana Pukhalskaya, MD