Podoplanin, E11

Podoplanin is a 38 kDa type I transmembrane mucoprotein with several O-glycosylation sites. Such proteins have been found as receptors for selectins which mediate inflammatory cell adhesion. It was initially identified on the foot processes of glomerular epithelial cells and has been linked to the flattening of foot processes in experimental puromycin-induced nephrosis (hence the name podoplanin, as in pes planus, flat foot)². It is also expressed by lymphatic but not blood vessel endothelium. Podoplanin is a target gene of the homeobox gene Prox1, a master gene controlling the development of lymphatic progenitors from embryonic veins⁶. Podoplanin deficiency results in congenital lymphedema and impaired lymphatic vascular patterning⁶.

Immunohistochemical expression

• Normal tissues: mesothelium, osteocytes, glandular myoepithelial cells, bile duct cells of the liver, ependymal cells, granulosa cells of ovarian follicles, and stromal reticular cells and follicualr dendritic cells of lymphoid tissue⁶.

• Lymphangioma

• Kaposi sarcoma

• Some angiosarcomas

Antipodoplanin is said to produce more clear immunoreactivity with less background staining that does D2-40⁷. Otherwise Podoplanin and D2-40 show very similar results¹:

			Podoplanin	D2-40
	Mesothelioma	epithelioid	25/29 (staining was seen in the same 25 cases that showed positivity with D2-40)1, 3/33	25/29 (better differentiated tumours show thick continuous membrane staining. In poorly differentiated tumours, membrane staining is discontinuous or staining is dot-like. Intracytoplasmic globoid staining may occur.)1
		biphasic	4/5 (positivity confined to the epithelioid component)1, 1/13	4/5 (positivity confined to the epithelioid component)1
		sarcomatoid	0/61	0/61
		peritoneal deciduoid	1/13
	Adenocarcinoma	lung	0/241,0/63	0/241
		ovary	0/171	0/171
		endometrium	0/51	0/51
		breast	0/101, 0/50 (40 invasive ductal, 10 invasive lobular)3	0/101
		pancreas	0/51	0/51
		stomach	0/51,0/83	0/51
		colon	0/101	0/101
		biliary tract	0/201
		kidney	0/101	0/101
		prostate	0/51	0/51
		ovary	0/61
		thyroid	0/31	0/31
	Adenomatoid tumour		2/21	2/2 (staining is of the apical cell membrane)1
	Squamous carcinoma	lung	0/101, 0/13	0/101
		maxillary sinus	0/23
		skin	0/13
	Neuroendocrine tumour	carcinoid	0/23
		phaeochromocytoma	0/33
	Angiosarcoma		2/51	2/51
	Synovial sarcoma	biphasic	4/6 (positivity confined to the epithelioid component)1	4/6 (positivity confined to the epithelioid component)1
		monophasic	0/61	0/61

Diagnostic utility

• A potential marker for epithelioid mesotheliomas, useful in the differentiation from adenocarcinoma⁴.

• Differentiation of primary skin adnexal carcinomas from adenocarcinoma metastatic to the skin, using the antibody D2-40⁵.

References

¹ Ordonez NG D2-40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma. Hum Pathol 2005; 36:372-80

² Breiteneder-Geleff S, Matsui K, Soleiman A, et al. Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis. Am J Pathol 1997; 151:1141-52

³ Kimura N,Kimura I. Podoplanin as a marker for mesothelioma. Pathol Int 2005; 55:83-6

⁴ Ordonez NG. Immunohistochemical diagnosis of epithelioid mesothelioma: an update. Arch Pathol Lab Med 2005; 129:1407-14 FULL TEXT

⁵ Liang H, Wu H, Giorgadze TA, et al. Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin. Am J Surg Pathol 2007; 31:304-10

⁶ Schacht V, Dadras SS, Johnson LA, et al. Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. Am J Pathol 2005; 166:913-21 FULL TEXT

⁷ Kimura N,Kimura I. Podoplanin as a marker for mesothelioma. Pathol Int 2005; 55:83-6

This page last revised 25.5.2008.

©SMUHT/PW Bishop