General
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• Widely expressive dipeptidase with various clinical features (see below)

Terminology
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• Also called dipeptidyl-peptidase IV, DPP4, DDPIV, adenosine deaminase complexing protein 2 (OMIM #102720)

Physiology
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• Costimulatory molecule in T cell activation and proliferation
• Also regulates various chemokines and cytokines
• Cleaves amino-terminal dipeptides
• Key role in cell adhesion and invasion (BMC Cancer 2013;13:517), plays a role in cell spreading and migration
• Either soluble in plasma or present on cell surface

Clinical features
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• Acute kidney transplant rejection: associated with increased serum CD26, and CD26 inhibition reduces acute and accelerated rejection (Adv Exp Med Biol 2003;524:133)
• Colorectal carcinoma: marker of poor prognosis (PLoS One 2014;9:e98582, PLoS One 2014;9:e107470)
• Endometrial carcinoma: reduced expression (Am J Obstet Gynecol 2003;188:670)
• HIV infection: may have protective role (Virol J 2010;7:343)
• Lung: soluble CD26 in serum/pleural fluid may distinguish pleural mesothelioma (lower values) from pulmonary adenocarcinoma (PLoS One 2014;9:e115647)
• Lung: may function as tumor suppressor in non small cell lung carcinoma (Int J Cancer 2004;109:855)
• Lymphoma, T cell: absence of CD26 staining on peripheral blood CD4+ T cells by flow cytometry may be useful for diagnosis (Am J Clin Pathol 2001;115:885, but see Am J Clin Pathol 2008;129:146)
• Pregnancy: blastocyst implantation may occur by binding of endometrial CD26 to embryonal fibronectin (Mol Hum Reprod 2006;12:491)
• Prostate cancer: possible poor prognostic marker (J Res Med Sci 2013;18:647)
• Thyroid carcinoma: increased expression (Diagn Cytopathol 2002;26:366, Am J Clin Pathol 1991;96:306)

Uses by pathologists
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• No significant uses at this time

Micro images
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Colon: normal

Kidney: proximal tubules

 

Prostate: carcinoma

Skin: melanoma versus deep penetrating nevi

Positive staining - normal
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• Activated T and B cells, basophils, macrophages, NK cells, thymocytes (mature)
• Epithelium: endometrium, hepatocytes, lung, prostate, renal proximal tubular cells, small intestine
• Also cytotrophoblast and extravillous trophoblast (J Clin Endocrinol Metab 2002;87:4287), biliary canaliculae, endothelial cells, fibroblasts, mesothelial cells (Oncology 2002;63:158), splenic sinus lining cells

Positive staining - disease
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• Esophageal adenocarcinoma and Barrett's metaplasia (Hum Pathol 1999;30:1291)
• Prostate carcinoma, thyroid anaplastic carcinoma (reduced expression in undifferentiated vs. differentiated areas (Am J Clin Pathol 2006;125:399)
• Wilm's tumor (Hum Pathol 1990;21:536)

Negative staining
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• Normal thyroid gland, T cells in peripheral blood of mycosis fungoides / cutaneous T cell lymphoma (40%, BMC Clin Pathol 2002;2:5)

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