Somatic isoform of angiotensin I-converting enzyme in the pathology of testicular germ cell tumors

Retained fetal expression of angiotensin I-converting enzyme (ACE, CD143) h as recently been shown in intratubular germ cell neoplasms (IGCN) and invas ive germ cell tumors (GCT), suggesting the somatic isoform (sACE) as a char acteristic component of neoplastic germ cells. We analyzed the distribution of sACE in 159 testicular GCT, including 87 IGCN. sACE protein was determi ned by immunohistochemistry (MAb CG2) on routinely formalin-fixed and paraf fin-embedded tissue sections, supplemented by mRNA expression analysis usin g in situ hybridization. These data were compared with those obtained by ge rm cell/placental alkaline phosphatases (PIAP; MAbs PL8-F6 and 8A9) employi ng an uniform score system for the evaluation of immunoreactivity (IRS; pos sible 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 expre ssion in adjacent seminomas (P = .032 for sACE; P = .005 for PIAP). Both sA CE and PIAP often showed a decreased and more heterogeneous but still moder ate expression in 91 classic seminomas (median IRS of 8) and were completel y absent in tumor cells of spermatocytic seminomas. Despite all similaritie s, we found sACE and PIAP differently regulated during GCT progression. Thi s was documented by a well-preserved expression of either sACE or PIAP or b oth in all classic seminomas, low PIAP immunoreactivity in metastasis of se minomas, and completely diverging expression patterns in nonseminomatous GC T. Our findings underline the close molecular relationship between IGCN and seminoma, and suggest sACE as an appropriate marker for seminomatous diffe rentiated tumors. Copyright (C) 2000 by W.B. Saunders Company.