Detection and Diagnostic Utilization of Placental Alkaline Phosphatase in Muscular Tissue and Tumors With Myogenic Differentiation

Abstract

Placental alkaline phosphatase (PLAP) is normally produced by primordial germ cells and syncytiotrophoblasts, and the detection of its expression has been useful in the diagnosis of germ cell tumors. We have recently observed PLAP immunoreactivity in normal human adult and fetal muscle tissue. Based on this observation, we explored the possible role of PLAP in the diagnosis of soft tissue tumors. A total of 271 tumors were studied. These included tumors with myogenic, neural, fibrous, myofibroblastic, lipomatous, neuroepithelial, perivascular, and epithelial differentiation. A formalin-fixed, paraffin-embedded section from each tumor was stained with PLAP monoclonal antibody using standard immunohistochemical methods preceded by antigen retrieval. In addition, western blotting with PLAP monoclonal antibodies was performed on fresh samples from a uterine leiomyoma, grossly normal myometrium, and placenta. Also, formalin-fixed sections of fetal skeletal muscle were labeled with double immunohistochemistry techniques using antibodies to myogenin and PLAP. Cytoplasmic PLAP reactivity was detected in all leiomyomas and rhabdomyosarcomas (100%), 7 of 15 (46%) leiomyosarcomas, 15 of 19 (79%) desmoplastic small round cell tumors, 2 of 15 (13%) gastrointestinal stromal tumors, 1 of 8 (13%) Wilms' tumors, 1 of 9 synovial sarcomas (9%), and 2 of 7 (29%) myofibroblastic tumors. No PLAP reactivity was detected in hyperplastic scars, nodular fasciitis, or the other remaining soft tissue and epithelial tumors. Double immunohistochemistry studies showed coexpression of myogenin and PLAP in fetal skeletal muscle cells, and western blot analysis showed a 70-kDa band in samples derived from grossly normal placenta, benign myometrium, and a uterine leiomyoma. PLAP immunoreactivity is detected in soft tissue tumors with known myogenic differentiation. PLAP immunoreactivity seems to relate to the degree of myogenic differentiation in soft tissue tumors and is more frequently expressed in cells with skeletal muscle differentiation and least in those with myofibroblastic features. The biologic function of PLAP in muscle and tumors with myogenic differentiation is unknown and merits further investigation. In addition to its role as a germ cell marker, PLAP may also be used as a myogenic marker in the diagnosis of soft tissue tumors.

True smooth muscle neoplasms of the gastrointestinal tract: morphological spectrum and classification in a series of 85 cases from a single institute

“…C-kitnegative GISTs usually show epithelioid phenotype, have a gastric location, lack desmin reactivity and commonly harbour PDGFRA mutations [20]. Consistent with a previous report [21], we documented a regular cytoplasmic reactivity for PLAP in almost all true smooth muscle neoplasms of the GI tract but in none of the GISTs examined. PLAP reactivity paralleled that of desmin.…”

Immunohistochemical Evaluation of Canine Ovarian Cysts

“…However, immunohistochemically, PLAP indicate a characteristic immunoreactivity for cysts of SES, which made differentiation possible. Although further examination is needed about the significance of PLAP positivity [6,7], the possibility that cysts of SES were among those difficult to classify was indicated by immunohistochemistry using PLAP antibody, as well as the view that the origin of cysts difficult to classify was cystic rete ovarii.…”

Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects

“…To define the origin of these membrane vesicles, the 'exosome'-association of placental-type alkaline phosphatase (PLAP), a plasma membrane enzyme linked with ovarian cancer, was also assayed ( Figure 3D). Recent analyses at the gene and protein levels have demonstrated PLAP expression in germ cell tumours and syncytiotrophoblasts and only rarely is the protein or message observed in normal adult tissues (Shigenari et al, 1998;Goldsmith et al, 2002). All 'exosome' isolates stained positive for PLAP, indicating the probable tumour origin of these membrane materials.…”