Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibin is a peptide hormone produced by ovarian granulosa cells and by granulosa cell tumors. Serum inhibin measurements have been used as a biochemical marker of the presence or progression of ovarian granulosa cell tumors and their metastases. In the current study, an antibody against the alpha-subunit of human inhibin was used to stain 16 cases of ovarian adult granulosa cell tumors, 15 cases of other ovarian sex cord-stromal tumors, and 51 cases of a range of ovarian and extraovarian neoplasms, many of which may mimic granulosa cell tumor. There was diffuse strong cytoplasmic staining of all cases of adult granulosa cell tumor. Diffuse positive staining also was observed in all Leydig cell tumors, and there was focal staining in a proportion of fibrothecomas. There was focal weak staining of one case of ovarian clear cell carcinoma but no staining of other ovarian and extraovarian neoplasms. Immunohistochemical staining with antibodies against inhibin is of value in the diagnosis of granulosa cell tumor and in the distinction of this neoplasm from others that may mimic it. The antibody also may be useful for the confirmation of late metastasis of granulosa cell tumor, especially when the previous history is not known.
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PMID:Immunohistochemical staining of ovarian granulosa cell tumors with monoclonal antibody against inhibin. 930 27

Inhibins (alpha and beta heterodimers) and activins (beta homodimers) are related peptides with opposing biologic action on gonadotropin regulation. They serve as components of the pituitary-gonadal feedback system. Although sex-cord stromal tumors can usually be distinguished from ovarian epithelial tumors or their metastases by morphology or by using antibodies against intermediate filaments, the diagnosis remains difficult in rare situations in such cases as sarcomatoid granulosa-theca cell tumors, ovarian small cell carcinomas, or soft-tissue sarcomas. A total of 28 sex cord-stromal tumors of the ovary and 43 non-sex cord-stromal tumors were immunohistochemically evaluated for the presence of alpha and beta subunits of inhibin and activin. For comparison, 10 normal adult gonads including seven ovaries with hilar regions and three testes also were examined. Immunoreactivity for both alpha and beta subunits of inhibin/activin was identified in both non-neoplastic and neoplastic granulosa, Sertoli, Leydig, hilar and luteinized theca cells, with the strongest immunoreactivity in Leydig and hilar cells. One of three Sertoli-Leydig cell tumors that showed a sarcomatoid growth pattern and one sex-cord tumor with annular tubules also were immunoreactive for both subunits. For non-sex cord stromal-derived ovarian tumors, alpha subunit immunoreactivity was negative in all but two of five ovarian mucinous tumors. Weak immunoreactivity for beta subunit was found in most ovarian surface epithelial carcinomas, two of four colonic, and one of three pancreatic carcinomas. No immunostaining was found in nonspecialized gonadal stromal or interstitial cells, thecal cells, germ cells, ovarian small cell carcinomas, carcinoid tumors, dysgerminomas, or leiomyosarcomas. Immunostaining of alpha subunit (inhibin alpha), but not of beta subunit could serve as a sex cord-stromal differentiation marker because alpha subunit alone is largely confined to sex cord-stromal lesions with the exception of some ovarian mucinous tumors. Further studies are needed to define the usefulness of this sex cord-stromal differentiation marker in the practice of surgical pathology. Coexpression of alpha and beta subunits in sex cord-stromal elements suggests that dimeric inhibin is expressed in these cells.
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PMID:Alpha and beta subunits of inhibin/activin as sex cord-stromal differentiation markers. 942 Oct 93

The authors retrospectively tested the potential value of paraffin-reactive monoclonal antibodies (A103 against melan-A, T311 against tyrosinase) and antibody KBA62 as immunohistochemical markers for amelanotic metastatic melanomas. The study cases included 72 amelanotic metastases of known cutaneous melanomas, 59 poorly differentiated carcinomas, 73 sarcomas of varying histogenesis, 4 Leydig cell tumors, 10 high-grade lymphomas, and 6 plasmoblastic/anaplastic myelomas. The results were compared with immunostainings for S-100 protein and HMB-45. HMB-45, antimelan-A, and antityrosinase showed almost identical staining results, with a sensitivity of 0.85 for HMB-45 and of 0.86 for both antimelan-A and for antityrosinase. HMB-45 and antityrosinase both had a specificity of 1.00; the specificity of antimelan-A was 0.95 as a result of a positive reaction in three of three adrenocortical carcinomas and four of four Leydig cell tumors. KBA62 stainings resulted in a sensitivity of 0.86 for melanomas. A positive immunoreactivity of KBA62 alone had a specificity of only 0.83, but in conjunction with anti-S-100 protein (sensitivity, 1.00; specificity, 0.87) and anticytokeratin 8/18/19 (CK), a KBA62+/S-100+/CK- immunophenotype identified all except one of the melanoma cases that were negative for the three melanocyte-specific markers with a specificity of 0.99. In conclusion, we found comparable immunohistochemical sensitivities of HMB-45, antityrosinase, and antimelan-A for a highly specific identification of approximately 85% of amelanotic metastatic melanomas on paraffin sections. Melanomas that were negative for all of these specific markers might be sensitively and specifically detected with anti-S-100 protein and KBA62.
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PMID:Tyrosinase, melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas on paraffin sections. 972 May 2

Genital neoplasms in the male horse are relatively uncommon. Squamous cell carcinomas and squamous papillomas are the most commonly diagnosed neoplasms of the penis and prepuce. Geldings appear to be overrepresented for these types of neoplasms, and accumulation of smegma may be a contributing factor. Early diagnosis and treatment are essential for salvaging these organs before lesions become excessively large and invasive or are allowed to metastasize. Newer treatment modalities such as 5-fluorouracil appear to be promising alternatives to surgical excision. Although generally considered to be uncommon, testicular tumors may occur more frequently than previously thought and have the potential for devastating effects on stallion fertility. Cryptorchidism appears to play a role in the development of equine testicular tumors, especially teratomas. Seminoma is by far the most common testicular tumor of the mature stallion. Seminomas are rapidly growing tumors with a greater potential to metastasize in the horse than in other domestic species. Leydig cell and Sertoli cell tumors have been reported but are relatively rare in the stallion. Orchiectomy is the standard treatment for most testicular tumors. In certain circumstances, however, such as neoplasia occurring in the only functional testis, local cryotherapy of testicular tumors may prolong the breeding career of an affected stallion.
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PMID:Neoplasia of the male reproductive tract. 989 22

We reported the case of a 35-year-old man with Klinefelter's syndrome and a malignant Leydig cell tumor of the testis. Bilateral gynecomastia and right testicular enlargement led the patient to seek medical assistance. Despite initial orchidectomy two years later the patient developed lung and iliac lymph node metastases. The tumor appeared to be refractory to chemotherapy and to hormonal treatments including op'DDD. Finally, the patient died within 20 months of developing metastases. Leydig cell tumor is an exceedingly rare tumor, especially when associated with Klinefelter's syndrome. This association as well as presentation, pathologic features, hormonal abnormalities, clinical course and response to therapy of malignant Leydig cell tumors are discussed.
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PMID:Malignant Leydig cell tumor of the testis associated with Klinefelter's syndrome. 1065 Jul 98

Leydig cell tumors of the testis are rare, mostly presenting as a testicular mass or as endocrinological symptoms. Here, three patients who were admitted for investigation of primary infertility and one patient presenting with a testicular mass are reported. The histological features were reviewed and an immunohistochemical study was done using a panel of antibodies against cytokeratin, vimentin, inhibin A, S-100, Ki-67, follicle-stimulating hormone, luteinizing hormone, prolactin, p53, bcl-2, and c-erbB2. The latter case (lost during follow up of metastatic disease) demonstrated massive tumor necrosis, extension through the tunica albuginea, and a high mitotic activity and MIB-1 score. Only this malignant case was bcl-2 positive. Of the two oncogenic markers studied, none of the cases were positive for c-erb2, while p53 was positive in more than 50% of cells in the malignant case and in one case of infertility with a large tumor, hemorrhage, focal necrosis and atypical cytological features. We recommend the evaluation of infertile men for Leydig cell tumors, and we believe that a panel of antibodies, including Ki-67, p53 and bcl-2, used for immunohistochemical analysis could be of diagnostic value in the identification of malignant and borderline cases of Leydig cell tumor.
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PMID:Leydig cell tumor of the testis: comparison of histopathological and immunohistochemical features of three azoospermic cases and one malignant case. 1188 32

We report 19 Leydig cell tumors (LCTs) of the testis with adipose differentiation (n = 12) and/or spindle cell growth (n = 8) in patients 28-70 years of age; three tumors with adipose differentiation showed psammomatous calcifications, two of which also had foci of ossification. In eight tumors fat-like cells apparently derived from lipid accumulation within neoplastic Leydig cells and appeared as focal to prominent clusters in a background of vacuolated, neoplastic Leydig cells. The fat-like cells were usually immunoreactive for Leydig cell markers (inhibin-alpha, calretinin, and melan-A) but were typically strongly positive for the adipose tissue marker, S-100 protein, supporting a hybrid cell phenotype. Four tumors had fat of stromal derivation. In two of these there were intermixed mature adipocytes, but in two others only lipoblastic cells were present. These four tumors lacked vacuolated, neoplastic Leydig cells, and the fat cells in the single case studied were negative for inhibin-alpha and melan-A but positive for S-100. Three of the 12 LCTs with adipose differentiation were clinically malignant, and each had several of the established malignant features. Eight tumors with spindle cells occurred in men 34-70 years of age. Two tumors had ill-defined fascicles of spindle cells, and three showed prominent edematous to myxoid areas with spindle-shaped tumor cells. Two additional tumors had a fibroma-like spindled component that blended with islands of more plump, polygonal to spindle-shaped Leydig cells. Finally, one tumor had foci resembling an unclassified sarcoma that merged with conventional LCT; the spindle cell component in this case did not react for Leydig cell markers in contrast to the spindle cells in five of the six other cases in which immunostains were performed. Spindle cell differentiation, by itself, did not appear to have prognostic significance. Of the six patients with available follow-up, two developed metastases, but their tumors had malignant features apart from spindle cells; the remaining four patients were disease free at a mean of 3.6 years. Awareness of these unusual patterns in LCTs may prevent misinterpretation of fat admixed with neoplastic Leydig cells as evidence of extratesticular growth (a criterion for malignant LCT) may help avoid misdiagnosis of a LCT as a testicular "tumor" of the adrenogenital syndrome (which may contain fat) and may prevent misdiagnosis of a LCT with spindle cells as a sarcoma or unclassified sex cord-stromal tumor.
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PMID:Leydig cell tumors of the testis with unusual features: adipose differentiation, calcification with ossification, and spindle-shaped tumor cells. 1240 18

Through a brief introduction of inhibin history, characteristics of the antibody against inhibin, and normal tissue distribution of alpha-inhibin expression, this comprehensive review focuses on a practical approach to using alpha-inhibin in the differential diagnosis of ovarian sex cord-stromal tumors (SCSTs). Alpha-inhibin has become a most useful immunohistochemical marker of gonadal SCST, regardless if the tumors are primary, recurrent, or metastatic. However, pathologic diagnosis of individual SCST is still based largely on morphologic criteria. Alpha-inhibin immunohistochemical (IHC) staining should be used only when a difficult morphologic diagnosis is encountered. In this perspective, alpha-inhibin and other properly selected markers should be ordered at the same time. This is simply because alpha-inhibin is not specific for SCSTs. Caution should be exercised in the interpretation of alpha-inhibin-positive cells, because a wide variety of primary and metastatic ovarian tumors may contain significant numbers of alpha-inhibin-positive stromal cells. As with other immunohistochemical stains, a panel of stains and comparison with the corresponding hematoxylin and eosin (H&E) slides is necessary, especially when staining patterns and cellular localization are in question. The antibody will not help to differentiate tumors within the category of SCST. The pattern or the intensity of staining in SCSTs does not predict tumor behavior, although there is a tendency of loss of alpha-inhibin expression in poorly differentiated Sertoli or Sertoli-Leydig cell tumors. In cases where metastatic granulosa or Sertoli-Leydig cell tumors are a concern, positive alpha-inhibin staining is diagnostic, but a negative result does not rule out metastatic disease. Calretinin has been recently recognized as a more sensitive, but less specific marker for SCSTs and it may be used to recognize an inhibin-negative SCST. In this review, we have listed nine of the most commonly encountered clinical scenarios where alpha-inhibin and other markers could be used in diagnostic surgical pathology of ovarian tumors.
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PMID:Inhibin immunohistochemical staining: a practical approach for the surgical pathologist in the diagnoses of ovarian sex cord-stromal tumors. 1250 66

Prostate cancer cells contain specific receptors (VDR) for la,25-dihydroxyvitamin D (1alpha,25(OH)2D), which is known to inhibit the proliferation and invasiveness of these cells. These findings support the use of 1alph,25(OH)2D for prostate cancer therapy. However, because 1alpha,25(OH)2D can cause hypercalcemia, analogs of 1alpha,25(OH)2D that are less calcemic but which exhibit potent antiproliferative activity would be attractive as therapeutic agents. We studied four vitamin D compounds: 25-hydroxyvitaminD3 [25(OH)D3], which is converted to 1alpha,25(OH)2D3 in prostate cells, and three analogs of 1alpha,25(OH)2D3: EB1089, 19-nor-1alpha,25(OH)2D2 and hexafluoro-1alpha,25(OH)2D3 (F6-1alpha,25(OH)2D3). 19-nor-1alpha,25(OH)2D2 has been shown to be less calcemic than 1alpha,25(OH)2D3 in clinical trials. F6-1alpha,25(OH)2D3 has been shown to be 100-fold more active than 1alpha,25(OH)2D3 and to be longer-lasting in inhibiting keratinocyte proliferation in vitro. EB1089 has been shown to be less calcemic than 1alpha,25(OH)2D3 in rats implanted with Leydig cell tumors. For 25(OH)D3, 19-nor-1alpha,25(OH)2D2 and F6-1alpha,25(OH)2D3, we studied the in vitro effects and compared their activity to 1alpha,25(OH)2D3 on cellular proliferation by 3H-thymidine incorporation assay. In addition, we studied transactivation of the VDR in the presence of 25(OH)D3 and 19-nor-1alpha,25(OH)2D2 in prostate cells. For EB1089, we compared its inhibition of prostate cancer metastasis to that induced by 1alpha,25(OH)2D3 in vivo in the rat Dunning MAT LyLu prostate cancer model. We found that 1alpha,25(OH)2D3 and 19-nor-1alpha,25(OH)2D2 caused similar dose-dependent inhibition in 3H-thymidine incorporation into DNA in prostate cells and behaved similarly in the CAT reporter gene transactivation assay in PC-3/VDR cells. F6-1alpha,25(OH)2D3 is 10- to 50-fold more active than 1alpha,25(OH)2D3 in 3H-thymidine incorporation into DNA in the primary cultured prostate cells. Likewise, 25(OH)D3 had comparable antiproliferative activity to la,25(OH)2D3. In the rat model, tumor volumes and the number of metastases in the lungs were significantly reduced by both 1alpha,25(OH)2D3 (10.4 +/- 2.81 tumor foci) and EB1089 (7.7+/-1.29 tumor foci) compared to controls (22.7 +/- 1.98 tumor foci). Although serum calcium levels were significantly elevated in both 1alph,25(OH)2D3- and EB1089-treated rats, EB1089 was significantly less calcemic than 1alpha,25(OH)2D3 (12.59+/-0.21 mg/dl versus 14.47+/-.46 mg/dL; 1 microg/kg; p < 0.001). In conclusion, our data indicate that 25(OH)D3 and the three 1alpha,25(OH)2D analogs represent two different solutions to the problem of hypercalcemia associated with vitamin D-based prostate cancer therapies: 25(OH)D3 requires the presence of 25-hydroxyvitaminD-1alpha-hydroxylase, whereas 19-nor-1alpha,25(OH)2D2, F6-1alpha,25(OH)2D3 and EB1089 do not. These compounds may be good candidates for human clinical trials in prostate cancer.
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PMID:Evaluation of vitamin D analogs as therapeutic agents for prostate cancer. 1289 29

Calretinin is a calcium-binding protein expressed in different normal and neoplastic tissues. Early studies suggested that calretinin is a useful marker to differentiate adenocarcinomas from malignant mesotheliomas of the lung, but subsequent work has shown that calretinin can be expressed in several other tumor types. To systematically investigate the epidemiology of calretinin expression in normal and neoplastic tissues, we used tissue microarrays (TMAs) to analyze the immunohistochemically detectable expression of calretinin in 5233 tissue samples from 128 different tumor categories and 76 different normal tissue types. At least 1 case with weak expression could be found in 74 of 128 (58%) different tumor types and 46 entities (36%) had at least 1 tumor with strong positivity. In normal tissues, a particularly strong expression was found in Leydig cells of the testis, neurons of the brain, theca-lutein and theca interna cells of the ovary, and mesothelium. In tumors, strong calretinin expression was most frequently found in malignant mesotheliomas (6 of 7), Leydig cell tumors of the testis (5 of 5), adenomas of adrenal gland (5 of 9), and adenomatoid tumors (4 of 9). In summary, calretinin is frequently expressed in many different tumor types. Metastases of various different origins must be included in the differential diagnosis of calretinin-positive pleura tumors.
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PMID:Calretinin expression in human normal and neoplastic tissues: a tissue microarray analysis on 5233 tissue samples. 1460 32


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