Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma

Abstract

Podoplanin, a mucin-like transmembrane sialoglycoprotein, promotes platelet aggregation and may be involved in cancer cell migration, invasion, metastasis, and malignant progression. Podoplanin/aggrus is highly expressed in testicular seminoma, suggesting that it may be a sensitive marker for testicular seminomas. Here we investigated the expression of podoplanin in central nervous system (CNS) germ cell tumors (GCTs) by immunohistochemical staining of tumor samples from 62 patients. In 40 of 41 (98%) germinomas (including germinomatous components in mixed GCTs), podoplanin was diffusely expressed on the surface of germinoma cells; lymphocytes, interstitial cells, and syncytiotrophoblastic giant cells were negative for podoplanin. Except for immature teratomas (12/17; 71%), podoplanin expression was absent in non-germinomatous GCTs, including seven teratomas, seven embryonal carcinomas, seven yolk sac tumors, and seven choriocarcinomas. In immature teratomas, focal podoplanin staining was observed in fewer than 10% of immature squamous and columnar epithelial cells. Thus, podoplanin expression may be a sensitive immunohistochemical marker for germinoma in CNS GCTs. As such, it may be useful for diagnosis, for monitoring the efficacy of treatment, and as a potential target for antibody-based therapy.

The Platelet Aggregation-Inducing Factor Aggrus/Podoplanin Promotes Pulmonary Metastasis

“…Third, Aggrus staining was observed in the metastatic lesions when the lung tissues were stained with our pre- viously generated YM-1 monoclonal antibody that could specifically recognize human Aggrus but not mouse Aggrus. 24,25,28 At high-power magnification, drifted tumor cell clump in the venule showed strong membranous staining ( Figure 5D, inset). In addition, the Aggrus-expressing cells made a mass with platelets, leukocytes, and erythrocytes ( Figure 5D, arrow, inset).…”

“…16 Because Aggrus/podoplanin is expressed on the lymphatic endothelium but not on blood vessel endothelium, it is also widely used in histopathology as a specific marker for lymphatic endothelium and lymphangiogenesis. 17 Aggrus expression has been shown to be up-regulated in a number of different cancers, including squamous cell carcinomas (oral cavity, 16 lung, 18 skin, 19 and head and neck 20 ), granulosa cell tumors, 19 mesotheliomas, 21 testicular seminomas, 22 central nervous system tumors, [23][24][25] and lobular breast cancers, 26 suggesting that increased expression of Aggrus is associated with tumor malignancy and poor clinical outcome. 20 We previously showed expression of Aggrus-induced platelet aggregation with no requirement for plasma components.…”

High-level expression of podoplanin in benign and malignant soft tissue tumors: Immunohistochemical and quantitative real-time RT-PCR analysis

“…Strong podoplanin immunoreactivity was detected in primary and metastatic seminoma and testicular germ-cell tumors of young adults derived from intratubular germ cell neoplasia and carcinoma in situ (6,28,29). Podoplanin expression is strongly expressed in pilocytic astrocytomas, glioblastomas, and primary central nervous system germ cell tumors (30)(31)(32). It is also strongly expressed in epidermal squamous cell carcinoma (33), oral leukoplakia (34)(35)(36), and skin adnexal carcinomas (37), whereas podoplanin is negative in metastatic adenocarcinomas and histiocytic neoplasms (38).…”

Podoplanin is a negative regulator of Th17 inflammation

“…It is highly expressed on lymphatic endothelial cells, fibroblastic reticular cells, follicular dendritic cells, alveolar type I epithelial cells, thymic epithelial cells, and kidney podocytes (13)(14)(15)(16)(17). Additionally, PDPN has been described on tumor cells of germ cell tumors, squamous cell carcinomas, mesotheliomas, and glioblastoma multiforme (18)(19)(20)(21)(22). PDPN upregulation has been reported in keratinocytes treated in vitro with TGF-β, IL-6, IL-22, or IFN-γ, (23) as well as in the synoviocytes, the fibroblast-like mediators of inflammatory tissue destruction, of rheumatoid arthritis patients (24).…”