HSD3B1 as a novel trophoblast-associated marker that assists in the differential diagnosis of trophoblastic tumors and tumorlike lesions

Trophoblastic tumors and tumorlike lesions can be confused with a variety of nontrophoblastic tumors; therefore, a trophoblast-associated marker that is expressed in all types of trophoblastic lesions is useful in differential diagnosis. In this report, we assessed the potential of hydroxyl-δ-5- steroid dehydrogenase (HSD3B1), an enzyme that catalyzes the oxidative conversion of δ-5-3 β-hydroxy steroids to the δ-4-3-keto configuration and that is involved in steroid hormone synthesis, as a diagnostic trophoblastic marker. First, the gene expression profile of HSD3B1 was analyzed in silica using serial analysis of gene expression in the database deposited in the public domain and found that HSD3B1 was not expressed in 159 libraries of breast, lung, colorectal, pancreatic, ovarian carcinomas, and a wide variety of normal adult and fetal tissues. Second, an immunohistochemical analysis was performed using a commercially available anti-HSD3B1 monoclonal antibody on paraffin sections. HSD3B1 immunoreactivity was detected in intermediate trophoblast and syncytiotrophoblast in 21 early placentas, 18 complete hydatidiform moles, 67 trophoblastic tumors, including placental site trophoblastic tumors, epithelioid trophoblastic tumors, and choriocarcinomas, and 28 tumorlike lesions including placental site nodules and exaggerated placental site. HSD3B1 immunoreactivity was diffuse and intense in the majority of trophoblastic lesions with the exception of a few choriocarcinomas. In contrast, only 3 (<1%) of 319 nontrophoblastic carcinomas from the uterus, lung, and breast reacted with the HSD3B1 antibody. Moreover, the immunoreactivity in these lesions was focal and weak. In conclusion, as compared with other trophoblastic markers, HSD3B1 is highly specific and sensitive, being expressed in all types of trophoblastic lesions but not in a variety of nontrophoblastic tumors of the uterus, lung, and breast.