The expression of placental alkaline phosphatase (PLAP) and PLAP‐like enzymes in normal and neoplastic human tissues

Abstract

SJHD is in receipt of a research fellowship from the Danish Medical Research Council. Hamilton-Dutoit, S. J., Lou, H. & Pallesen, G. The expression of placental alkaline phosphatase (PLAP) and PLAP-like enzymes in normal and neoplastic human tissues. An immunohistological survey using monoclonal antibodies. APMIS 98: 797-8 1 1, 1990.The immunohistological expression of placental alkaline phosphatase (PLAP) and PLAP-like enzyme was studied in frozen sections from a wide variety (n = 254) of normal and malignant tissues using monoclonal antibodies reactive with PLAP (H3 17) and PLAP/PLAP-like enzyme (H I7E2; H3 15). PLAP/PLAP-like reactivity was seen in normal thymus, and foetal and neonatal testis, and in 2 1 out of 22 malignant germ cell tumours (GCTs), but was also found in normal endocervix, normal Fallopian tube and in 28 out of 167 non-GCTs (particularly in ovarian and proximal gastrointestinal tract tumours). Positivity for true PLAP (as demonstrated with H317) was seen in term placenta, in endocervix, and in Fallopian tube (but not in other normal tissues) and was commonly found in ovarian and proximal gastrointestinal tract tumours. Reactivity with H3 17 was unusual in malignant GCTs (2 out of 22 cases). These findings confirm that PLAP/PLAP-like positivity is a highly sensitive immunohistological marker for malignant GCTs, but one which by itself is of only moderate specificity. Furthermore, expression of true PLAP is rare in GCTs and favours instead an origin from the ovary or proximal gastrointestinal tract. The results also indicate that the predominant heat-stable alkaline phosphatase species in normal foetal and neonatal testis, and in thymus has a similar immunohistological profile to that found in malignant GCTs, and is a PLAP-like enzyme ("germ cell alkaline phosphatase") distinct from true PLAP. The occurrence of this marker in GCTs would appear to reflect increased eutopic production of an enzyme present in trace amount in corresponding normal tissues rather than a genuine example of ectopic expression.

SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

“…10,11 Many nongerm cell tumors have been reported to be immunohistochemically positive for PLAP. 12,13,46 In this study, only 6 of 15 (40%) metastatic yolk sac tumors were found to be positive for PLAP staining, which is similar to other studies. 10,13,19 Three of 6 PLAP-positive cases in the current study demonstrated only 1% to 2% cells stained with this marker.…”

“…39,40 Earlier markers such as PLAP, AFP, C-KIT, and CD30 lack adequate sensitivity and specificity for metastatic germ cell tumors. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Recently, novel stem cell markers such as OCT4, NANOG, and SOX2 have emerged as more sensitive and specific markers for metastatic germ cell tumors (seminoma and embryonal carcinoma), but to our knowledge they do not label any metastatic yolk sac tumors 9,11,24,25,41 ; this is a significant deficiency because these tumors can mimic many other tumor types. In the current study, all metastatic seminomas, dysgerminomas, embryonal carcinomas, and yolk sac tumors were found to be strongly positive for SALL4 in >90% of tumor cells; only 1 case of yolk sac tumor had 80% tumors cells found to be strongly positive for SALL4.…”

“…10,11 Many types of nongerm cell tumors have also been reported to be positive for PLAP. 12,13 CD30 is positive in embryonal carcinoma, but it is also expressed in anaplastic lymphoma, Hodgkin lymphoma, carcinoma, and melanoma. 14,15 In addition, CD30 expression is lost in approximately two-thirds of embryonal carcinomas after chemotherapy.…”

VASA Is a Specific Marker for Both Normal and Malignant Human Germ Cells

“…Although it is a fairly sensitive marker for classic seminoma/dysgerminoma, GCAP/PLAP is not expressed in spermatocytic seminoma (Dekker et al, 1992). The diagnostic usefulness of GCAP/PLAP is further limited by lack of specificity, because it is frequently expressed in nongerm cell tumors such as ovarian carcinoma (in as many as half of ovarian papillary serous carcinomas) (Nakopoulou et al, 1995) and other neoplasms, particularly those of gastrointestinal origin (Hamilton-Dutoit et al, 1990). In addition, GCAP/PLAP is expressed in several normal tissues (Hamilton-Dutoit et al, 1990).…”

“…The diagnostic usefulness of GCAP/PLAP is further limited by lack of specificity, because it is frequently expressed in nongerm cell tumors such as ovarian carcinoma (in as many as half of ovarian papillary serous carcinomas) (Nakopoulou et al, 1995) and other neoplasms, particularly those of gastrointestinal origin (Hamilton-Dutoit et al, 1990). In addition, GCAP/PLAP is expressed in several normal tissues (Hamilton-Dutoit et al, 1990). In contrast, the highly specific expression of VASA in normal germ cells and in specific subtypes of germ cell tumors (our study) suggests that VASA is likely to be a useful diagnostic marker with greater specificity than GCAP/PLAP.…”