the onco-foetal antigen M2A was identified as a 40 kDa
O-glycosylated glycoprotein recognized by the D2-40 Ab in foetal
gonocytes and Sertoli cells, podoplanin was first identified as a 38
kDa transmembrane glycoprotein in the podocytes of rat kidney.
Immunohistochemical studies of transfected cells have subsequently
shown that M2A and podoplanin, also designated Aggrus, gp36 and
T1A-2, are most likely identical proteins. Podoplanin acts as
receptor for selectins (which
mediate inflammatory cell adhesion) and is involved in cell
maturation and migration by filopodia formation (via the
downregulation of the activities of small Rho family GTPases).
Podoplanin has also been identified as a platelet
Podoplanin is demonstrated in virtually all cases of seminoma/dysgerminoma (but not in spermatocytic seminoma) as well as in pre-invasive precursor testicular germ cell neoplasia (carcinoma in situ or intratubular germ-cell neoplasia, IGCN). Embryonal carcinoma may show a more limited membranous reaction. Podoplanin is found in the large majority of epithelioid and biphasic malignant mesothelioma (~90%), adenomatoid tumour and synovial sarcoma (epithelioid part). Podoplanin is also demonstrated in virtually all cases of Kaposi sarcoma, furthermore in a subset of angiosarcoma, and the vacuolated cells of haemangioblastoma (while the endothelial cells of differentiated haemangiomatous tumours are always negative), in most cases of squamous cell carcinoma (head and neck, lung, uterine cervix), (myo-)fibroblastic tumours, leiomyosarcoma and gastrointestinal stromal tumour, almost all cases of chondromatous tumours (but not chordoma), follicular dendritic reticulum cell sarcoma, and in a large proportion of primary brain tumours (astrocytoma, glioblastoma, ependymoma, choroid plexus tumours, PNET, meningioma)
Adenocarcinomas are usually negative. In serous carcinoma, the
protein has been detected in 13-65% of the cases! In pleural
effusions the frequency of podoplanin positive adenocarcinomas has
been up to 50%.
Podoplanin is a very useful marker in the differentiation between malignant mesothelioma and adenocarcinoma (at least in histological specimens), and the identification of seminoma/dysgerminoma/IGCN (where it appears to be more sensitive and specific than, e.g., placental alkaline phosphatase, OCT3/4 and CD117). Podoplanin is also the primary choice in the visualization and quantification of lymphatic vessels and tumor invasion in the vessels (e.g., in the desmoplastic stroma of carcinomas, where both lymphangiogenesis and lymphatic tumour spread is associated with lymph node metastases and a worse prognosis).
mAb D2-40 is a well functioning Ab. HIER is
mandatory for an optimal staining result.
Bassarova AV, Nesland JM,
Davidson B. D2-40 is not a specific marker for cells of mesothelial
origin in serous
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T, Miura M.
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