Inhibin-α, CD99, HEA125, PLAP, and chromogranin immunoreactivity in testicular neoplasms and the androgen insensitivity syndrome

Harvard University, Cambridge, Massachusetts, United States
Human Pathlogy (Impact Factor: 2.77). 09/2000; 31(9):1055-1061. DOI: 10.1053/hupa.2000.16237


We investigated 115 testicular and 3 epididymal tumors and 6 cases of the complete androgen insensitivity syndrome (AIS) for the expression of inhibin-α, CD99, HEA125, PLAP, and chromogranin, using monoclonal antibodies and standard immunhistochemical techniques. Inhibin-α was detected in the neoplastic cells in 27 of 27 primary Leydig cell tumors (LCTs), 1 of 1 metastatic LCT, 6 of 20 Sertoli cell tumors (SCTs), 4 of 5 juvenile granulosa cell tumors (JGCTs), and 2 of 5 unclassified sex cord–stromal tumors (USCSTs). Except for 2 choriocarcinomas, the choriocarcinomatous component of 1 mixed germ cell tumor, and a small focus of inhibin-positive syncytiotrophoblast in 1 embryonal carcinoma, inhibin-α immunoreactivity was not present in the neoplastic cells of the 38 remaining testicular germ cell tumors; 11 B-cell and 1 T-cell lymphomas; 1 granulocytic sarcoma; and 1 rhabdomyosarcoma of the testis; 1 adenoma of the rete testis, and 3 adenomatoid tumors of the epididymis. Inhibin-α immunoreactivity was present in the Sertoli cells and Leydig cells in 5 testicular hamartomas and in 1 Sertoli cell adenoma in 6 cases of AIS; both Sertoli and Leydig cells were also positive in the extranodular testicular parenchyma present in 2 of these cases. CD99 was detected in 10 of 15 primary LCTs, 1 of 7 SCTs, 3 of 5 JGCTs, and in 1 of 5 USCSTs but was not found in any tumor outside the sex cord–stromal category. HEA125 immunostaining was not detected in sex cord–stromal tumors; however, 3 of 12 seminomas, 3 of 12 embryonal carcinomas, 6 of 8 yolk sac tumors, and 1 of 2 teratomas were HEA125 positive. PLAP was not detected in sex cord–stromal tumors except for 4 of 15 primary LCTs but was present in most germ cell tumors. Chromogranin immunostaining was present in the sex cord–like element in 1 of 5 USCSTs, 1 of 8 YSTs, 1 of 2 teratomas, and in 1 of 1 rete adenoma, and in normal adjacent rete testis. In conclusion, although inhibin-α and PLAP, and, to a somewhat lesser extent, CD99 and HEA125 immunostaining are helpful in the differential diagnosis of certain testicular neoplasms that are difficult to distinguish on morphologic grounds, chromogranin is far less helpful in this context. HUM PATHOL 31:1055-1061.

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    • "Inhibin-alpha, a subunit of inhibin, is secreted mainly from testicular Sertoli cells with an additional small contribution from Leydig cells [4,34]. Although little is known about the cells secreting inhibin in primary testicular tumors of humans and older animals [5,9,16], inhibin immunoreactivity has been biochemically estimated in human and canine testicular tumors. In the current seminoma series, inhibin-alpha was observed in the cytoplasm of tumors cell in 45% of the cases. "
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    ABSTRACT: Primary testicular tumors are the most common causes of cancer in male dogs. Overall, the majority of canine patients should be cured by testicular surgery. However, tumor markers are not well-known in veterinary medicine. We sought to determine using immunohistochemistry whether the combined human testicular tumor markers (placental alkaline phosphatase, OCT3/4, CD30, alpha-fetoprotein, inhibin-alpha, vimentin, c-KIT, and desmin) are expressed in canine seminomas and Sertoli cell tumors (SCTs). We examined 35 canine testicular tumors, 20 seminomas and 15 SCTs. c-KIT was expressed markedly in canine seminomas. Both inhibin-alpha and vimentin were expressed significantly in canine SCTs. The results of this study demonstrate differences and similarities between tumor marker expression of testicular tumors in dogs and humans. All the main markers in current routine use are discussed as well as potential useful markers for benign and malignant tumors, and tumor progression.
    Full-text · Article · Apr 2009 · Journal of Veterinary Science
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    • "Cx43 and inhibin-a double immunostaining clearly identified these cell clusters as residual Leydig cell clusters, in addition to endothelial cells, as the main source of nonneoplastic cells in seminoma expressing Cx43. Inhibin-a was chosen as this subunit is known to be expressed in human Leydig cells [44]. Furthermore, immunohistochemical stainings revealed no immunoreactive signals for Cx43 between seminoma cells, suggesting that these cells are unable to synthesize Cx43 protein and unable to communicate through Cx43 gap junction channels, and Western blot analyses performed with seminomatous tissue showed only a weak immunoreactive band for Cx43 at 45 kDa. "
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    ABSTRACT: Carcinoma in situ (CIS) represents the preinvasive stage of human germ cell tumors, but the mechanism leading to pubertal proliferation and invasive malignancy remains unknown. Among testicular gap junctional proteins, connexin 43 (Cx43) represents the predominant Cx, and, previously, an inverse correlation between synthesis of Cx43 protein and progression of tumor development was detected. In the present study, using cDNA microarray analysis, in situ hybridization, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) from tissue homogenates, RT-PCR from microdissected tubules with normal spermatogenesis and CIS, and seminoma cells from invasive seminoma, we asked whether reduction of Cx43 protein is accompanied by a change of Cx43 transcripts. We detected a significant downregulation of Cx43 at mRNA level in Sertoli and germ cells starting in seminiferous tubules infiltrated with CIS and resulting in a complete loss in seminoma cells. It was demonstrated, that downregulation of Cx43 expression in neoplastic human testis takes place at the transcriptional level and starts in CIS. This reduction of Cx43 expression further suggests that early intratubular derangement in Cx43 gene expression and disruption of intercellular communication between Sertoli cells and/or Sertoli and preinvasive tumor cells may play a role in the progression phase of human seminoma development.
    Full-text · Article · Jul 2006 · Neoplasia (New York, N.Y.)
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    ABSTRACT: Objective: The expression of Mullerian inhibiting substance (MIS), CD99 (MIC-2 gene product), and HEA125 in ovarian tumors is potentially useful for diagnostic purposes. Methods: We studied the expression of MIS, CD99, and an epithelial cell-associated antigen recognized by antibody HEA125 in a series of 179 ovarian tumors using monoclonal or polyclonal antibodies and standard immunohistochemical techniques. Results: MIS was consistently detected in primary and metastatic sex cord tumors with annular tubules (SCTAT) (n=9). 3 of 9 adult granulosa cell tumors (AGCT) 4 of 8 juvenile granulosa cell tumors (JGCT), 3 of 9 Sertoli cell tumors (SCT), 2 of 2 unclassified sex cord tumors, 2 of 7 steroid cell tumors, 1 of 1 gonadoblastoma (sex cord cells positive, germ cells negative), 3 of S female adnexal tumors of probable wolffian origin (FATPWO), and 2 of 4 small cell carcinomas of the hypercalcemic type (SCCHCT) were also MIS positive. In contrast, 9 thecomas, 10 fibromas, 10 fibrosarcomas, S sclerosing stromal tumors (SST), and 6 Sertoli-Leydig cell tumors (SLCT) were MIS negative. All 11 primary and metastatic JGCT were CD19 positive. In addition, 1 of 13 AGCTs, 3 of II thecomas, 3 of II SSTs, 3 of 11 SCTs, 2 of 10 SLCTs, 2 of 12 SCTATs, 1 of 1 gynandroblastoma, 1, of 2 unclassified sex cord tumors, and 4 of 12 SCCHCTs were also CD99 positive. However, 11 fibromas, 10 fibrosarcomas, 9 steroid cell tumors, 5 gonadoblastomas, and 10 FATPWOs were CD99 negative. Likewise, except for weak focal CD99 immunostaining in 1 of 3 yolk sac tumors (YST), all 16 remaining germ cell tumors and all 18 borderline or malignant epithelial-stromal tumors were negative. HEA125 immunoreactivity was detected in 2 of 11 thecomas, 1 of 11 SCTs, 4 of 10 SLCTs, 1 of 2 unclassified sex cord tumors, 1 of 10 FATPWOs, 4 of 12 SCCHCTs as well as in most germ cell tumors and epithelial-stromal tumors. 13 AGCTs, 11 JGCTs, 11 fibromas, 10 fibrosarcomas, 11 SSTs, 12 SCTATs, 1 gynandroblastoma, 9 steroid cell tumors, and 5 gonadoblastomas were HEA125 negative. Conclusion: Our findings indicate that MIS is a marker of sex-cord differentiation and may be useful as a serum tumor marker for certain sex cord tumors, especially SCTAT. Although the detection of MIS and CD99 in some SCCHCTs and FATPWOs might argue in favor of a sex cord origin, the histogenesis of these tumors remains unclear. Although inhibin-cr has previously been shown to be a more sensitive marker of sex-cord differentiation, a panel of immunohistochemical markers including MIS, CD99 and HEA125 may be helpful in the differential diagnosis of certain ovarian neoplasms.
    No preview · Article · May 2001 · Geburtshilfe und Frauenheilkunde
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