title: Somatic isoform of angiotensin I-converting enzyme in the pathology of testicular germ cell tumors.
abstract: Retained fetal expression of angiotensin I-converting enzyme (ACE, CD143) has recently been shown in intratubular germ cell neoplasms (IGCN) and invasive germ cell tumors (GCT), suggesting the somatic isoform (sACE) as a characteristic component of neoplastic germ cells. We analyzed the distribution of sACE in 159 testicular GCT, including 87 IGCN. sACE protein was determined by immunohistochemistry (MAb CG2) on routinely formalin-fixed and paraffin-embedded tissue sections, supplemented by mRNA expression analysis using in situ hybridization. These data were compared with those obtained by germ cell/placental alkaline phosphatases (PIAP; MAbs PL8-F6 and 8A9) employing an uniform score system for the evaluation of immunoreactivity (IRS; possible values from 0 to 12). Expression of sACE and PIAP was found in all 87 analyzed IGCN (IRS > 4, median IRS of 12). Heterogeneous staining patterns were not related to the type of adjacent GCT but correlated with low expression in adjacent seminomas (P =.032 for sACE; P =.005 for PIAP). Both sACE and PIAP often showed a decreased and more heterogeneous but still moderate expression in 91 classic seminomas (median IRS of 8) and were completely absent in tumor cells of spermatocytic seminomas. Despite all similarities, we found sACE and PIAP differently regulated during GCT progression. This was documented by a well-preserved expression of either sACE or PIAP or both in all classic seminomas, low PIAP immunoreactivity in metastasis of seminomas, and completely diverging expression patterns in nonseminomatous GCT. Our findings underline the close molecular relationship between IGCN and seminoma, and suggest sACE as an appropriate marker for seminomatous differentiated tumors. HUM PATHOL 31:1466-1476.
authors.affiliation: Department of Pathology, Justus-Liebig-University of Giessen, Germany.
authors.forename: F E
authors.initials: FE
authors.lastname: Franke
authors.forename: K
authors.initials: K
authors.lastname: Pauls
authors.forename: L
authors.initials: L
authors.lastname: Kerkman
authors.forename: K
authors.initials: K
authors.lastname: Steger
authors.forename: T
authors.initials: T
authors.lastname: Klonisch
authors.forename: R
authors.initials: R
authors.lastname: Metzger
authors.forename: F
authors.initials: F
authors.lastname: Alhenc-Gelas
authors.forename: E
authors.initials: E
authors.lastname: Burkhardt
authors.forename: M
authors.initials: M
authors.lastname: Bergmann
authors.forename: S M
authors.initials: SM
authors.lastname: Danilov
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase; D018236:Carcinoma, Embryonal / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002822:Choriocarcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D018240:Endodermal Sinus Tumor / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D058851:GPI-Linked Proteins; D018237:Germinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013724:Teratoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013736:Testicular Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D013737:Testis / Q000201:enzymology / Q000473:pathology
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D058851:GPI-Linked Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental; D007703:Peptidyl-Dipeptidase A