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N Sasano

Publications and source records attributed to N Sasano.

At least 19 recordsLinked to original sources
PubMed1992

Testicular sex cord-stromal lesions: immunohistochemical analysis of cytokeratin, vimentin and steroidogenic enzymes.

We have studied immunolocalization of all steroidogenic enzyme involved in sex steroids biosynthesis, P-450 side chain cleavage (P-450scc), 3 beta hydroxy steroid dehydrogenase (3 beta-HSD), P-450 17 alpha hydroxylase (P-450(17 alpha)) and P-450 aromatase (P-450arom) and that of vimentin and cytokeratin in 14 cases of testicular sex cord-stromal tumours (6 Leydig cell tumours, 5 Sertoli cell tumours, 2 fibromas and 1 granulosa cell tumour) as well as 4 cases of hyperplasia (2 Leydig and 2 Sertoli). Leydig cell tumour expressed all four steroidogenic enzymes examined, indicating that this tumour can synthesize oestrogen from cholesterol. In 2 cases of Sertoli cell tumour, the tumour cells with clear cytoplasm and without Reinke's crystals expressed P-450ssc, 3 beta-HSD and P-450(17 alpha), suggesting the capability of androgen production in these tumour cells. Fibromas and granulosa cell tumour were negative for the enzymes examined. In immunohistochemistry of intermediate filaments, Leydig cell tumours demonstrated only vimentin. Sertoli cells in hyperplasia and non-neoplastic testis expressed only vimentin but Sertoli cell tumours expressed both cytokeratin and vimentin. Cytokeratin immunoreactivity was correlated with morphological epithelial differentiation in Sertoli cell tumour. These findings in testicular Sertoli cell tumour are considered to represent the multiple differentiation capacity of this neoplasm. Immunohistochemical study of steroidogenic enzymes and intermediate filaments provided new insight into neoplastic steroidogenesis and the differentiation capacity of testicular sex cord-stromal neoplasms.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

De novo expression of aromatase in gastric carcinoma. Light and electron microscopic immunohistochemical and immunoblot study.

We have performed immunohistochemical and immunochemical studies of steroidogenic enzymes involved in estrogen biosynthesis in 30 cases of gastric carcinoma in order to investigate possible in situ production of estradiol (E 2) in carcinoma cells. Positive incidence of immunoreactivity for E 2, testosterone (T), cholesterol side-chain cleavage enzyme (P-450 scc) and aromatase (P-450 arom) were 17/30 (56.7%), 11/30 (36.7%), 3/30 (10.0%) and 23/30 (76.7%), respectively on light microscopy. Estrogen receptor (ER) immunoreactivity was not observed in any of the 30 cases examined. Normal gastric mucosa was negative for P-450 arom and P-450 scc. Examination of serial sections revealed that immunoreactivity of E 2 and P-450 arom were located in the same cells of carcinomatous glands. Immunoelectron microscopy demonstrated that E 2 and P-450 arom were located along the membrane and cisternae of smooth endoplasmic reticulum (sER). Western blot analysis showed one major band of 55 kDa of P-450 arom in the gastric carcinoma tissues examined. Retrospective analysis of immunohistochemistry of E 2 in 108 cases of gastric carcinoma revealed that E 2 positive carcinoma cases were likely to demonstrate better survival rate than negative cases. These results above strongly suggest that E 2 is produced by de novo expressed aromatase in gastric carcinoma cells and is possibly involved in the biology of gastric carcinoma cells.

Aromatase↗
PubMed1992

Primary pigmented nodular adrenocortical disease (PPNAD): immunohistochemical and in situ hybridization analysis of steroidogenic enzymes in eight cases.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare but an interesting adrenocortical disorder associated with ACTH-independent hypercortisolism. We have studied eight cases of the adrenals with PPNAD by immunohistochemistry of all steroidogenic enzymes involved in cortisol biosynthesis (P-45scc, 3 beta-HSD, P-450c21, P-45017 alpha, and P-45011 beta) and also by performing in situ hybridization of P-45017 alpha in seven cases in order to localize the sites of specific steroidogenesis in this unique disorder. Immunoreactivity of all the enzymes examined was intense in almost all of the cells in adrenocortical nodules, especially the cells with abundant eosinophilic cytoplasm in all the cases examined. The internodular cortex, which demonstrated atrophy in five cases, normal appearance in two cases and hyperplasia in one case, was negative for the enzymes with an exception of 3 beta-HSD. Hybridization signals of P-45017 alpha were condensed over the nodules in in situ hybridization study, suggestive of an increased production of the enzyme itself in cortical cells of the nodules. These results may be consistent with autonomous cortisol production by the nodular cells and indicate that almost all of the cells in the nodules produce cortisol, which can also explain the presence of hypercortisolism despite small sizes of adrenals in PPNAD. Immunoreactivity of steroidogenic enzymes is observed in a small cluster of cortical cells with abundant eosinophilic cytoplasm located at the zona reticularis but not in adjacent non-nodular cortex, which may support an abnormal development of the zona reticularis as a possible pathogenesis of this disorder.

3-Hydroxysteroid Dehydrogenases↗
PubMed1991

Adrenocortical oncocytoma. A true nonfunctioning adrenocortical tumor.

We studied three cases of adrenocortical neoplasms that were detected incidentally after radiological examination of the abdomen. These cases did not demonstrate any clinical evidence of adrenocortical abnormalities, such as virilization. Macroscopically, the tumors were light to dark tan on cut surface. Light-microscopic examination revealed compact cells with abundant lipid-sparse eosinophilic cytoplasm and occasional enlarged nuclei. In one case, ultrastructural observation demonstrated abundant mitochondria. Immunohistochemical examination of all of the adrenocortical steroidogenic enzymes showed that none of the cases had immunoreactivity. No mitotic activity and no vascular invasion was observed. The postoperative course were uneventful. The follow-up interval varied from 8 to 27 months. These three neoplasms apparently represent the first reported cases of adrenocortical oncocytoma. They can be considered true nonfunctioning adrenocortical neoplasms because steroidogenic enzymes required for corticosteroid biosynthesis were not expressed in the tumor cells.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

Immunohistochemical study of 3 beta-hydroxysteroid dehydrogenase in sex cord-stromal tumors of the ovary.

3 beta-Hydroxysteroid dehydrogenase (3 beta-HSD), which converts pregnenolone to progesterone, was localized immunohistochemically in 18 thecomas, 23 fibromas, 5 granulosa-cell tumors, 5 sclerosing stromal tumors, and 2 steroid-cell tumors. Immunohistochemical study of estrogen, progesterone, and testosterone was also performed in serial sections of thecomas and fibromas. In thecomas, immunoreactivity of 3 beta-HSD was observed only in luteinized theca cells and thecomatous tumor cells with abundant pale to vacuolated cytoplasm but not in spindled tumor cells and thecomatous tumor cells with small to moderate amounts of pale to vacuolated cytoplasm. Immunoreactivity of steroids was not observed in thecomas except for testosterone immunoreactivity in one case. No immunoreactivity of steroids or the enzyme was present in fibromas. No tumor cells were positive for 3 beta-HSD in any of the cases of granulosa-cell tumor examined. Immunoreactivity of 3 beta-HSD was present in cells in steroid-cell tumors and polygonal tumor cells with prominent cytoplasmic vacuoles in two cases of sclerosing stromal tumor. Thus, 3 beta-HSD can be a good immunohistochemical marker of steroidogenesis in functioning ovarian neoplasms.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

Immunolocalization of 3 beta-hydroxysteroid dehydrogenase in human ovary.

Immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was performed in 55 cases of morphologically normal human ovaries by using a specific polyclonal antibody against purified human placental 3 beta-HSD. In small developing follicles, immunoreactivity was observed only in the theca interna but also became recognizable in the membrana granulosa with development of the follicle. At a late stage of folliculogenesis, the intensity of the 3 beta-HSD activity in the membrana granulosa was nearly equal to that of theca interna in 2 or 3 large follicles examined. One to several layers of theca interna cells just beneath membrana granulosa did not demonstrate any immunoreactivity of 3 beta-HSD or that of cytochrome P-450 17 alpha-hydroxylase. These unstained theca interna cells did not appear to be directly involved in ovarian steroidogenesis and might be designated as 'enzymically inactive theca interna cells.' Marked immunoreactivity was observed in luteinized theca and granulosa cells of the corpus luteum.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

Expression of intermediate filaments in neuroendocrine tumors.

Expression of 160-kilodalton (kd) neurofilament, cytokeratin, and vimentin was immunohistochemically investigated in 45 pheochromocytomas, 12 medullary thyroid carcinomas, and 12 pancreatic islet cell tumors. Four mixed neuroendocrine-neural tumors, two multiple endocrine neoplasia type I tumors, and two multiple endocrine neoplasia type II tumors were included in this study. Neurofilament immunoreactivity was demonstrated in 45 (100%) of the pheochromocytomas, 10 (83%) of the medullary thyroid carcinomas, and 11 (92%) of the islet cell tumors. Cytokeratin and vimentin were detectable in 29% and 24% of the pheochromocytomas, 100% and 25% of the medullary thyroid carcinomas, and 67% and 25% of the islet cell tumors, respectively. Neurofilament was the most frequently detected intermediate filament in the neuroendocrine tumors. Cytokeratin was seen in the intra-adrenal but not the extra-adrenal pheochromocytomas. Coexpression of neurofilament and cytokeratin was common in the neuroendocrine tumors, and occasionally vimentin was also expressed simultaneously. There were no characteristic differences in the expression of intermediate filaments between multiple endocrine neoplasia type I or II tumors and sporadic-type tumors or between metastatic tumors and nonmetastatic tumors.

Adenoma, Islet Cell↗
PubMed1990

Nucleolar organizer regions in human adrenocortical disorders.

A silver colloid technique to demonstrate nucleolar organizer region-associated proteins (AgNORs) was performed on sections of 39 human adrenal glands, including normal adrenal cortex, bilateral adrenocortical hyperplasia, adenoma, and carcinoma. In mineralocorticoid and glucocorticoid-producing adrenocortical cells, the mean number of AgNORs per nucleus was lowest in the normal adrenal gland and highest in adenoma, with statistically significant differences. The mean number of AgNORs in bilateral adrenocortical hyperplasia was placed between that of normal adrenal and adenoma. AgNOR numbers in morphologically and clinically verified adrenocortical carcinoma (12 cases) were not different from those in adenoma (17 cases). In adrenal cortex, AgNOR numbers may be correlated with increased steroid hormone production but appear to be of little value in discerning malignancy in adrenocortical neoplasms.

Adenoma↗
PubMed1989

Coexpression of cytokeratin, neurofilament and vimentin in carcinoid tumors.

The immunohistochemical expression of intermediate filaments was investigated in 56 carcinoid tumors from 50 cases including 31 rectal and 25 non-rectal sites. Cytokeratin was the most frequently expressed in 55 of the tumours. Only one tumour of the stomach was negative for cytokeratin. Neurofilament (68 kd and 160 kd) was positive in 25 (44.6%) tumours with no preferential pattern of expression in particular tumours. Vimentin was positive in 18 out of the 31 rectal carcinoids (58%), and 3 of the 25 non-rectal carcinoids (12%). There was a significant difference in vimentin immunoreactivity between rectal and non-rectal carcinoids. The coexpression of cytokeratin and neurofilament was 44.6% and that of cytokeratin and vimentin was 37.5%. The coexpression of all three types of intermediate filament was 35.5% in rectal carcinoids, but 8% in non-rectal carcinoids. The present study revealed coexpression of cytokeratin, neurofilament and vimentin in carcinoids and an especially high incidence of vimentin expression in those of rectal origin.

Carcinoid Tumor↗
PubMed1989

Immunohistochemical studies of steroidogenic enzymes (aromatase, 17 alpha-hydroxylase and cholesterol side-chain cleavage cytochromes P-450) in sex cord-stromal tumors of the ovary.

Aromatase, 17 alpha-hydroxylase, and cholesterol side-chain cleavage P-450 cytochromes (P-450AROM, P-450(17 alpha,) and P-450SCC, respectively) were immunohistochemically localized in nine granulosa cell tumors, 15 thecomas, ten Sertoli-Leydig cell tumors, two steroid cell tumors, five fibromas, and five sclerosing stromal tumors. In the thecomas, P-450SCC and P-450(17 alpha) were positive in luteinized theca cells and in cells with vacuolated cytoplasm, while P-450AROM was not observed. In the steroid cell tumors, all the P-450 cytochromes were intensely stained. P-450SCC and P-450(17 alpha) were present in cells with vacuolated cytoplasm in two cases of sclerosing stromal tumor. P-450AROM was weakly demonstrated in one of the granulosa cell tumors. P-450(17 alpha,) P-450SCC, and P-450AROM were all faintly stained in the Sertoli-Leydig cell tumors. No P-450 cytochrome immunoreactivity was observed in any fibroma.

Aromatase↗
PubMed1989

Immunohistochemical study of cytochrome P-45017 alpha in human adrenocortical disorders.

Cytochrome P-450 specific for steroid 17 alpha-hydroxylation (P-45017 alpha) was immunolocalized in normal and hyperfunctioning adrenal glands of pigs, bovines, and humans, using a specific IgG fraction raised against the enzyme. P-45017 alpha was present in the zona fasciculata (ZF) and zona reticularis (ZR), but not in the zona glomerulosa (ZG), in pig, bovine, and human adrenal glands. In the adrenal glands of patients with Cushing's disease, the positive immunoreactivity to P-45017 alpha was intense in ZF and ZR, particularly in cortical micronodules, corresponding to the sites of active steroidogenesis. Cells of hyperplastic ZG and outer ZF in the adrenal glands of idiopathic hyperaldosteronism were negative for P-45017 alpha. In aldosteronoma, positive immunoreactivity was observed in some tumor cells, which is consistent with cortisol production and its responsiveness to ACTH in aldosteronoma. In the attached adrenal glands of aldosteronoma, the immunoreactive P-45017 alpha was clearly present in the inner ZF and ZR, suggesting persistent androgen production. In Cushing's adenoma, the positive immunoreactivity was intense in tumor cells, and the ZR of the attached adrenal glands was weakly immunoreactive.

Adenoma↗
PubMed1989

Immunohistochemical analysis of cytochrome P-450 17 alpha-hydroxylase in pig adrenal cortex, testis and ovary.

Cytochrome P-450 specific for steroid 17 alpha-hydroxylation (P-450(17 alpha] was immunohistochemically observed in pig adrenal cortex, testis and ovary by the biotin-streptavidin method using a specific antibody against P-450(17 alpha) purified from neonatal pig testis. In the adrenal cortex, P-450(17 alpha) was present in the zona fasciculata and reticularis while no immunoreactivity was observed in the zona glomerulosa, confirming the absence of 17-hydroxylated steroid synthesis in the zona glomerulosa. In the testis, P-450(17 alpha) was present exclusively in Leydig cells and immunoreactivity was absent in seminiferous tubules. In the ovary, immunoreactivity was observed only in the theca interna but not in the membrana granulosa of follicles. Among the tissues examined, the relative intensity of immunoreactivity was greatest in the Leydig cells, and progressively less in theca interna cells, outer fasciculata cells and inner fasciculata and reticularis cells.

Adrenal Cortex↗
PubMed1989

Immunohistochemical demonstration of cholesterol side-chain cleavage cytochrome P-450 in bovine and human adrenals.

Cytochrome P-450 specific for cholesterol side-chain cleavage (P-450SCC) was purified from the bovine adrenal and a specific antibody was raised in rabbits. The antiserum was applied for immunohistochemical visualization of the P-450SCC in the bovine and human adrenal cortex. The immunoreactivity was intense in the zona fasciculata (ZF) and reticularis (ZR) while weak in the zona glomerulosa (ZG) in the normal adrenals. In adrenocortical hyperplasia, a marked immunoreactivity was observed in the ZG in idiopathic hyperaldosteronism and the inner ZF and reticularis particularly in cells of micronodules in Cushing's disease, corresponding to cells with active steroidogenesis. In aldosteronoma and adenoma with Cushing's syndrome, P-450SCC was generally present in compact cells of adenomas.

Adenoma↗
PubMed1989

Immunohistochemical demonstration of adrenodoxin reductase in bovine and human adrenals.

Adrenodoxin reductase (ADR) was purified from bovine adrenocortical mitochondria and specific antibody was raised in rabbits. Immunohistochemical analysis of ADR was performed in the bovine and human adrenals. ADR was present in all of the zones in both bovine and non-pathological human adrenal cortex. In non-pathological human adrenals, the immunoreactivity was particularly prominent in the zona glomerulosa (ZG) and reticularis (ZR). Intensive immunoreactivity was observed in the ZG and some cells of the outer fasciculata and the ZR in the adrenal glands with idiopathic hyperaldosteronism. In adrenal glands with Cushing's disease, immunoreactivity was present in the compact cells of cortical micronodules. In all cases, sites of immunoreactivity correspond to sites of increased steroidogenesis. In aldosteronoma and cortical adenoma with Cushing's syndrome, the immunoreactivity was generally marked in compact cells but not in large cells with clear cytoplasm, ADR was present in the ZG and the ZR, and the ZG in the non-neoplastic adrenal glands attached to aldosteronoma and Cushing's adenoma, respectively. ADR was present in the compact cells in adrenocortical carcinoma clinically manifesting Cushing's syndrome.

Adrenal Gland Diseases↗
PubMed1989

What's new in the localization of sex steroids in the human ovary and its tumors?

It is important to understand the distribution of steroidogenesis in steroid producing tissues in order to obtain a better understanding of steroid metabolism. Recent advances in purification and subsequent generation of antibodies against cytochromes P-450 specific for steroid hormone biosynthesis have made it possible to localize the sites of steroidogenesis immunohistochemically. This review provides the localization of sex-steroid hormone biosynthesis in normal and pathological human ovaries including sex-cord stromal tumors, hyperthecosis and Brenner tumor, as determined by the tissue distribution of immunoreactivity of individual enzymes specific for different stages of the biosynthetic process.

Female↗
PubMed1989

Demonstration of neuroendocrine cells in ovarian mucinous tumors.

The frequency of argyrophil cells in mucinous cystadenocarcinomas, borderline tumors (MBT) and cystadenomas was 29.8% (14 of 47), 46.7% (7 of 15) and 11.1% (2 of 18), respectively. These were statistically higher than the frequencies in 17 clear cell carcinomas, 43 serous cystadenocarcinomas, and 24 metastatic carcinomas. Immunoreactive cells for serotonin, somatostatin, gastrin, pancreatic polypeptide, growth hormone-releasing hormone, metenkephalin, neuron-specific enolase, and chromogranin-A were detected in almost all these cases with argyrophil cells. However, immunoreactivities for glucagon, vasoactive intestinal polypeptide, and adrenocorticotropic hormone were negative in ovarian mucinous tumors. Immunohistochemical multiplicity of neurohormones was remarkable in 15 MBT (including 5 müllerian and 10 intestinal MBT) and it was not related to the number of argyrophil cells per unit tumor cells. Individual hormones demonstrated here seemed to be present in different cells, but certain cells were immunoreactive for both gastrin and somatostatin by double immunostaining. Based on the high frequency of endocrine cells, borderline tumors seemed to be unique in the spectrum of mucinous ovarian tumors.

Adenocarcinoma↗