Characterization and distribution of an oncofetal antigen (M2A antigen) expressed on testicular germ cell tumours

Abstract

M2A antigen is an oncofetal antigen associated with germ cell neoplasia, present in testis on fetal gonocytes and re-expressed on carcinoma in situ (CIS) and germ cell tumours. We developed a panel of monoclonal antibodies (mAb), M2A (IgG2a), D1-26 (IgG2b) and D2-40 (IgG1), to this antigen in order to characterize its structure and study its distribution among germ cell tumours. M2A antigen was purified by sequential lectin and antibody affinity chromatography and characterized as a monomeric M r 40 000 surface sialoglycoprotein, extensively glycosylated with O-linked carbohydrate structures, but devoid of N-linked sugars. Terminal sialic acid residues were required for reactivity with mAb M2A and D1-26, but not D2-40. Sections of 69 testicular germ cell tumours, fixed in formalin and embedded in paraffin, were stained with mAb D2-40 to examine the distribution of M2A antigen. Uniform membrane staining was observed in seminomas, and focal staining in 69% of embryonal carcinomas, 29% of teratomas and 25% of yolk sac tumours. CIS in the vicinity of all germ cell tumours also displayed uniform membrane staining. The characterization of M2A antigen, and the development of mAb which react with it in conventionally preserved archival specimens, provide important initiatives to study the origin and progression of germ cell neoplasia. © 1999 Cancer Research Campaign

D2-40 immunohistochemical analysis of pediatric vascular tumors reveals positivity in kaposiform hemangioendothelioma

“…The overall cellular distribution of the staining corresponded to the normal location of the M2A antigen (glycoprotein) on the cellular surface and within the Golgi complex. 12 One of 24 lesions was negative; however, this might have been due to the small size of the biopsy containing only one tumor lobule.…”

“…12 The carbohydrate structure of the antigen recognized by D2-40 is common for mucin-type glycoproteins that are widely expressed in normal and tumor cells. 20 Thus, although M2A was initially identified in fetal gonocytes, germ-cell tumors, and prepubertal Sertoli cells, [21][22][23] it is also present in a number of human cancer cell lines, including osteosarcoma and transitional cell carcinoma.…”

“…5 D2-40 is a monoclonal antibody raised against dysgerminoma that binds a membrane sialoglycoprotein M2A. 12 It has been observed that D2-40 selectively stains lymphatic endothelium in adult human tissue; this observation has been extended to finding D2-40 positivity in 'lymphangioma', Kaposi sarcoma and a subset of angiosarcoma, but not in benign tumors of blood vessels. 13 Recently, D2-40 immunopositivity was reported in hobnail hemangioma, suggesting that this tumor is of lymphatic origin.…”

Origins and molecular biology of testicular germ cell tumors

“…Despite the overexpression of this antigen, c-kit is rarely mutated in these tumors. Other antibodies, which immunoreact with IGCNU but are rarely used in clinical practice, include M2A and 43-F. 57,59,60 POU5F1 (Oct3/4) is a very interesting marker that was recently described. 61 The gene serves as a transcription factor and its product is expressed in pluripotent mouse and human embryonic stem cells and is downregulated during differentiation.…”

D2-40 and calretinin—a tissue microarray analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation

“…23,24 D2-40 is a novel monoclonal antibody that was reported to recognize a 40 kDa surface sialoglycoprotein expressed in germ cell neoplasia and fetal testicular gonocytes. 25 A recent investigation has demonstrated that this mucin-type glycoprotein is podoplanin. 26 Martín-Villar et al 28 and Ma et al 27 both described its human genome.…”