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PDPN

MIM.608863

Thursday 22 December 2005

Definition: PDPN encodes podoplanin (Aggrus, human gp36, T1A-2), a transmembrane glycoprotein expressed in lymphatic endothelium and various solid tumours.

Podoplanin, which is immunoreactive to D2-40 antibody, is reportedly expressed in lymphatic vessels in non-neoplastic tissues, and also in vascular and non-vascular tumors.

The deduced 162-amino acid PDPN protein (podoplanin) contains a putative transmembrane region, a protein kinase A (MIM.176911) phosphorylation site, and a protein kinase C (MIM.176960) phosphorylation site.

Expression in tissues

- Testis

M2A (D2-40), as c-KIT, has frequently been used as markers of germ cell tumors. However, comparative studies of their immunoreactivities in human fetal gonads have been limited.

In 12-week fetuses, c-KIT immunoreactivity is weak, but M2A immunoreactivity is consistently strong.

At 15 and 18 weeks of gestation, c-KIT immunoreactivity is found in most germ cells.

D2-40 is expressed in Sertoli cells as well as in germ cells, but is not expressed in ovarian follicles undergoing meiosis.

D2-40 appears to be a more useful marker of germ cells than c-KIT in human fetal testis and ovary at the second trimester.

D2-40 is also reactive in fetal Sertoli cells, but its expression is consistently weaker than in germ cells.

Age

- fetal testis 39 weeks

References

- A comparison between D2-40 and c-KIT immunohistochemistry for the human fetal testis and ovary at the second trimester of gestation. Jin ZW, Kim YG, Yu HC, Murakami G, Fujimiya M, Cho BH. Okajimas Folia Anat Jpn. 2010 May;87(1):1-4. PMID: 20715565

Expression in tumors

- lymphatic tumors
- primary cutaneous carcinomas (17255777)

  • sebaceous carcinomas
  • squamous cell carcinomas
  • porocarcinomas
  • trichilemmal carcinomas
  • skin adnexal carcinomas (NOS, not otherwise specified)
  • majority of benign skin adnexal tumors

Diagnostic pathology

- PDPN is over-expressed in testicular pre-invasive intratubular lesion, carcinoma in situ (CIS) compared to normal adult testis.

  • Testicular germ-cell tumours of young adults are derived from a pre-invasive intratubular lesion, carcinoma in situ (CIS).
  • Podoplanin (PDPN) has a function in developing testis, most likely at the level of cell-cell interactions among pre-meiotic germ cells and immature Sertoli cells.

- Podoplanin is a useful diagnostic marker for epithelioid hemangioendothelioma of the liver. (18084256)

- Podoplanin is the only positive marker for chondrosarcoma. It can be used in the skull base chordoma vs chondrosarcoma differential diagnosis. (18820665)

- Podoplanin is a better immunohistochemical marker for sarcomatoid mesothelioma than calretinin. (18162779)

- Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin. (17255777)

- Podoplanin (D2-40) is a marker for follicular dendritic cell tumors. (17951199)

- Podoplanin lymphatic density and invasion correlate with adverse clinicopathologic and biological factors and survival in neuroblastomas. (22588067)

Antibodies

- M2A (D2-40) antigen is identical to gp36 (podoplanin, Aggrus, T1A-2).

References

- Podoplanin lymphatic density and invasion correlate with adverse clinicopathologic and biological factors and survival in neuroblastomas. Ramani P, Somerville MS, May MT. Am J Surg Pathol. 2012 Jun;36(6):908-15. PMID: 22588067

- Oakley GJ, Fuhrer K, Seethala RR. Brachyury, SOX-9, and podoplanin, new markers in the skull base chordoma vs chondrosarcoma differential: a tissue microarray-based comparative analysis. Mod Pathol. 2008 Sep 26. PMID: 18820665

- Fujii T, Zen Y, Sato Y, Sasaki M, Enomae M, Minato H, Masuda S, Uehara T, Katsuyama T, Nakanuma Y. Podoplanin is a useful diagnostic marker for epithelioid hemangioendothelioma of the liver. Mod Pathol. 2008 Feb;21(2):125-30. PMID: 18084256

- Podoplanin is a better immunohistochemical marker for sarcomatoid mesothelioma than calretinin. Padgett DM, Cathro HP, Wick MR, Mills SE. Am J Surg Pathol. 2008 Jan;32(1):123-7. PMID: 18162779

- Podoplanin (D2-40) is a novel marker for follicular dendritic cell tumors. Yu H, Gibson JA, Pinkus GS, Hornick JL. Am J Clin Pathol. 2007 Nov;128(5):776-82. PMID: 17951199

- Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin. Liang H, Wu H, Giorgadze TA, Sariya D, Bellucci KS, Veerappan R, Liegl B, Acs G, Elenitsas R, Shukla S, Youngberg GA, Coogan PS, Pasha T, Zhang PJ, Xu X. Am J Surg Pathol. 2007 Feb;31(2):304-10. PMID: 17255777

- Agarwal B, Saxena R, Morimiya A, Mehrotra S, Badve S. Lymphangiogenesis does not occur in breast cancer. Am J Surg Pathol. 2005 Nov;29(11):1449-55. PMID: 16224211

- Ordonez NG. D2-40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma. Hum Pathol. 2005 Apr;36(4):372-80. PMID: 15891998

- Nakano T, Nakashima Y, Yonemitsu Y, Sumiyoshi S, Chen YX, Akishima Y, Ishii T, Iida M, Sueishi K. Angiogenesis and lymphangiogenesis and expression of lymphangiogenic factors in the atherosclerotic intima of human coronary arteries. Hum Pathol. 2005 Apr;36(4):330-40. PMID: 15891993

- Schmid K, Birner P, Gravenhorst V, End A, Geleff S. Prognostic value of lymphatic and blood vessel invasion in neuroendocrine tumors of the lung. Am J Surg Pathol. 2005 Mar;29(3):324-8. PMID: 15725800