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H Sasano

Publications and source records attributed to H Sasano.

At least 235 records · Page 13Linked to original sources
PubMed1996

Aromatase and steroid receptors in gynecomastia and male breast carcinoma: an immunohistochemical study.

Hormonal factors have been implicated in the development of male breast disorders, including carcinoma and gynecomastia. We studied the expression of aromatase and estrogen (ER), progesterone (PR), and androgen (AR) receptors by immunohistochemistry in male breast carcinoma (15 cases) and gynecomastia (30 cases) to evaluate their possible significance in these disorders. Relatively strong aromatase immunoreactivity was observed in all cases of carcinoma, but in only 11 of 30 cases (37%) of gynecomastia. ER and PR expression was observed in the nuclei of ductal cells in all the cases of gynecomastia. More than 10% of the carcinoma cells were positive for ER and PR in 9 of 15 (60%) and 10 of 15 (67%) carcinomas, respectively. AR immunoreactivity was observed in nuclei of both epithelial and non-epithelial cells. AR was present in ductal or carcinoma cells in 13 of 15 (87%) cases of carcinoma and in all 30 (100%) cases of gynecomastia. The mean percentage of ER-, PR-, and AR-positive cells were significantly higher in gynecomastia than in carcinoma. There was a close association of AR with ER (P < 0.01) and PR (P < 0.01) in cases of gynecomastia, but there was a significant inverse correlation between AR and ER (P < 0.01) or PR (P < 0.05) expression in carcinoma cases. Increased aromatase expression in the stromal cells is considered to contribute to the increment in the in situ estrogen concentration and the development of male breast carcinoma.

Adult↗
PubMed1996

Localization of 11 beta-hydroxysteroid dehydrogenase type II in human epithelial tissues.

The enzyme 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2) confers specificity on the renal mineralocorticoid receptor by inactivating glucocorticoids. Mutations in this gene give rise to the syndrome of apparent mineralocorticoid excess, a congenital condition characterized by sodium retention, severe hypertension, and often by growth retardation. It is not known whether 11 beta HSD2 or another enzyme confers specificity in nonrenal sodium transporting epithelia, such as those in the sweat gland, salivary gland, and gastrointestinal tract. We previously have used the HUH23 antibody to localize 11 beta HSD2 in the human kidney, vascular smooth muscle cells, and placenta. In the present study, we have examined a range of human epithelia for the presence of 11 beta HSD2. In the skin, staining was seen in eccrine sweat glands and arterioles, whereas weak HUH23 immunostaining was observed in the epidermis. Staining was absent from sebaceous glands and hair follicles. In the parotid gland, the 11 beta HSD2 enzyme was present in striated and excretory ducts, whereas in the submandibular gland, it was found in striated and interlobular ducts. Acini, adipocytes, and associated tumor tissue did not stain with the HUH23 antibody. In the gastrointestinal tract, HUH23 stained ileal enterocytes, colonic absorptive cells, and epithelial goblet cells, whereas the rectum contained areas of staining and nonstaining absorptive cells. Gastrointestinal structures, such as the lamina propria, Peyer's patch, and goblet cells within the crypts of Lieberkuhn did not stain with the antibody. This study demonstrates the presence of 11 beta HSD2 in nonrenal sodium-transporting epithelia and describes a range of tissues affected in the syndrome of apparent mineralocorticoid excess.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Serum levels of dehydroepiandrosterone sulfate in patients with asymptomatic cortisol producing adrenal adenoma: comparison with adrenal Cushing's syndrome and non-functional adrenal tumor.

The reported number of adrenal incidentalomas has been increasing because of wider application of imaging techniques. Patients with asymptomatic cortisol producing adrenal adenoma (ASCA) which secretes cortisol without clinical evidence of Cushing's syndrome has been more frequently observed than previously assumed, and they have a risk of adrenal insufficiency after adrenalectomy. Therefore patients with incidentalomas should be screened for cortisol overproduction. The aim of this study is to discover an easy screening test to uncover ASCA. We investigated the hormone profiles of 4 patients with ASCA in comparison with 11 patients with non-functional adrenal tumor and 10 patients with adrenal Cushing's syndrome. We also investigated the expression of dehydroepiandrosterone sulfotransferase (DHEA-ST) in surgically removed attached non-neoplastic adrenal tissues by immunostaining, which was considered to represent the degree of suppression of the hypothalamo-pituitary-adrenal axis. Serum dehydroepiandrosterone sulfate (DHEA-S) levels of all the patients with ASCA and adrenal Cushing's syndrome were lower than those of healthy subjects of corresponding age, but they were within the normal range in the patients with non-functional adrenal tumors. The serum DHEA-S level reflects the degree of suppression of the normal adrenal gland by cortisol hypersecretion from adrenal tumors. But the serum level of DHEA-S decreases with age, and because the normal range of serum DHEA-S is low in elderly subjects, we should be careful to evaluate the level of DHEA-S in elderly patients with adrenal Cushing's syndrome or ASCA. The immunohistochemical study showed DHEA-ST expression was noticeably suppressed in the adjacent adrenal cortex in ASCA and adrenal Cushing's syndrome. The decreased expression of DHEA-ST may reflect autonomous neoplastic cortisol secretion and subsequent ACTH suppression in ASCA and adrenal Cushing's syndrome. A single measurement of plasma ACTH or measurement of ACTH response to corticotropin-releasing hormone was not enough to screen for ASCA because of the wide variation among the cases. Dexamethasone suppression test is essential in identifying ASCA and also a single determination of serum DHEA-S is easy and may be useful for the screening of ASCA in adrenal incidentalomas in young and middle aged subjects, and is especially useful for outpatients.

Adenoma↗
PubMed1996

Leydig cell tumor of the testis: analysis of testosterone production and secretion by three-dimensional histoculture.

We treated an 11-year-old boy with a testicular Leydig cell tumor. We analyzed the testosterone production of this tumor by immunolocalization of steroidogenic enzymes and in vitro three-dimensional histoculture. Spermatic venous blood from the tumor bearing testis had noticeably high concentrations of testosterone and androstenedione. The tumor had the characteristic ultrastructural features of steroid producing cells and was immunoreactive for P450scc (side chain cleavage), 3 beta HSD (hydroxysteroid dehydrogenase) and P450c17 (17 alpha-hydroxylase). Three-dimensional collagengel-supported histoculture demonstrated that the tumor tissue in the culture maintained its histologic architecture, expression of steroidogenic enzymes, and secretion of testosterone into the medium for up to 7 days in culture. Histoculture preserved in vitro testosterone production in this case of testicular Leydig cell tumor.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Incidentally discovered adrenocortical adenomas are not fully nonfunctioning: immunohistochemical and dispersed adrenocortical cell study.

To clarify the precise function of incidentally discovered adrenocortical adenoma, immunohistochemical and dispersed adrenal cell studies were performed. We have recently seen five patients with so-called nonfunctioning adrenocortical adenoma. Diurnal variation in plasma cortisol and suppression of plasma cortisol and urine 17-hydroxycorticosteroids in response to dexamethasone administration revealed adrenocortical function within normal limits in all cases, and no signs or symptoms of adrenal steroid hormone excess were evident. Since a high uptake of iodomethylnorcholesterol was recognized in each adrenal mass, it was supposed that these adrenal tumors produced steroid hormone to a certain extent, and each patient received unilateral adrenalectomy. P450c17, a key enzyme involved in cortisol production, was expressed in the tumor region in all cases in an immunohistochemical study. Upon in vitro steroidogenesis with dispersed adrenal cells in two cases, all steroid hormones measured except for aldosterone (progesterone, 17 alpha-hydroxyprogesterone, pregnenolone, 17 alpha-hydroxypregnenolone, 11-deoxycortisol, cortisol, 11-deoxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, dehydroepiandrosterone and androstenedione) were produced in a culture medium. The results indicated that these tumors possessed the capacity for cortisol production, which was in agreement with the results of an iodomethyl-norcholesterol scintigraphy. All patients with mild hypertension or diabetes mellitus had no signs or symptoms of steroid hormone excess, but they could potentially develop a steroid excess syndrome such as Cushing's syndrome in the future.

17-Hydroxycorticosteroids↗
PubMed1996

Adrenocorticotropin-independent bilateral macronodular adrenocortical hyperplasia: immunohistochemical studies of steroidogenic enzymes and post-operative course in two men.

We treated two men with Cushing's syndrome due to adrenocorticotropin (ACTH)-independent bilateral macronodular adrenocortical hyperplasia (AIMAH). In both patients, plasma ACTH was low and plasma cortisol was not suppressed by a high dose of dexamethasone (8 mg) but was remarkably responsive to exogenous ACTH. The adrenal glands were extremely enlarged and contained multiple nodules composed of large clear cells and small compact cells. The immunoreactivity of P-450(17) alpha was predominant in the small compact cells, while that of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was observed exclusively in the large clear cells. Among various adrenocortical disorders, differential expression of 3 beta-HSD and P-450(17) alpha in clear and compact cells has heretofore been demonstrated only in AIMAH. Total adrenalectomy was done for one patient, and partial adrenalectomy for the other. In the former patient, the normal diurnal rhythm of plasma ACTH was restored 11 months postoperatively. In the latter patient, the normal dynamics in the hypothalamic-pituitary-adrenal axis became evident 15 months after surgery. Thus AIMAH is apparently a primary adrenocortical disorder and is not due to abnormalities of the hypothalamus or pituitary.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Transforming growth factor-alpha, epidermal growth factor, and epidermal growth factor receptor in human testis obtained from biopsy and castration: immunohistochemical study.

We analyzed expression of transforming growth factor (TGF)-alpha, epidermal growth factor (EGF) and their receptor, EGF receptor (EGFR), by immunohistochemistry in the human testis to determine the possible roles of these growth factors in human testicular function. Specimens were obtained from 17 patients including 9 patients with infertility, 4 patients with prostatic carcinoma and 4 patients with contralateral testicular tumor. EGF immunoreactivity was positive in the hyperplasic Leydig cells of one patient but negative in the other cases. On the other hand, strong TGF-alpha immunoreactivity was observed in Leydig cells, with weak staining in Sertoli cells and germ cells in cases with normal spermatogenesis. EGFR immunoreactivity was observed in the Leydig and peritubular cells, appearing as membrane staining. Marked immunoreactivity for TGF-alpha was observed in the Sertoli cells in testes with decreased spermatogenesis, especially in the Sertoli-cell-only syndrome. This finding may indicate a compensatory increase of TGF-alpha expression in the Sertoli cells accompanying a decrease in spermatogenesis. No significant correlation was found between the degrees of spermatogenesis and immunolocalization of the EGF receptor. These findings suggest that TGF-alpha is a locally produced growth factor that is involved in spermatogenesis in the human testis via an autocrine and/or paracrine mechanism.

Adolescent↗
PubMed1996

Bilateral aldosterone-producing adenomas in two patients diagnosed by immunohistochemical analysis of steroidogenic enzymes.

Bilateral adrenal aldosterone-producing adenomas (APA) are rare. It is important to distinguish bilateral APA from idiopathic hyperaldosteronism (IHA) which is due to bilateral hyperplasia of the adrenal cortex. We present two patients with bilateral APA in whom the diagnosis was made histochemically by analyzing steroidogenic enzymes. They showed hypokalemia, high plasma aldosterone concentration (PAC) and suppressed plasma renin activity (PRA). Bilateral adrenal tumors were represented by computed tomography, and surgical resection was performed. In both cases, cytochrome P-450 and other enzymes that were involved in aldosterone synthesis were found mainly in tumor, but little in the zona glomerulosa of the adjacent adrenals, which showed paradoxical hyperplasia. Such cases are difficult to distinguish from IHA. The two disorders were differentiated by immunohistochemical analysis of steroidogenic enzymes.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Primary aldosteronism with bilateral multiple aldosterone-producing adrenal adenomas.

A 41-year-old woman developed primary aldosteronism due to bilateral multiple aldosterone-producing adenomas (APA). She was suspected to have idiopathic hyperaldosteronism (IHA) 7 years previously. Although preoperative data suggest APA and IHA was suspected in a postoperative microscopic specimen, a definite clinical diagnosis could not be made. Cytochrome P-450 and other enzymes involved in aldosterone synthesis were found in the tumor portions but not in the zona glomerulosa of attached adrenals, which histopathologically showed "paradoxical hyperplasia". This was a rare case of bilateral multiple APA, which could be differentiated from IHA by immunohistochemical analysis of adrenal steroidogenic enzymes.

Adenoma↗
PubMed1996

Aromatase in human common epithelial ovarian neoplasms.

The expression of aromatase was evaluated in 44 ovarian carcinomas, 7 carcinomas of low malignant potential (LMP), and 14 benign adenomas. Aromatase immunoreactivity was observed in stromal cells in 35 of 44 (79.5%) ovarian carcinomas and 3 of 7 carcinomas of LMP. However, no immunoreactivity was pronounced at sites of frank invasion in ovarian carcinoma. To characterize aromatase in ovarian carcinoma, aromatase activity, mRNA expression, and alternative uses of exon 1 were determined. Quantitation of aromatase activity with the tritiated water method demonstrated 41.62 +/- 9.15 pmol/hour/mg protein in 11 ovarian carcinomas. The mean concentration of aromatase mRNA for 14 ovarian carcinomas was 3 +/- 4 amol/ng RNA, which significantly correlated with aromatase immunoreactivity. The alternative use of multiple copies of exon 1 was examined by reverse transcriptase polymerase chain reaction in 11 carcinomas. The transcript, mainly using exons 1c and 1d, was detected in 4 and 5 cases of carcinoma, respectively. Patterns of utilization of exon 1, however, did not significantly correlate with aromatase overexpression. These results suggest that aromatase is expressed in stromal cells of ovarian carcinoma but not in benign ovarian neoplasms. Increased aromatase expression in stromal cells of human ovarian carcinoma is, therefore, considered to play an important role in the biological behavior of these tumors by producing estrogens in situ as in other female sex-steroid-dependent neoplasms.

Adenocarcinoma↗
PubMed1996

17 beta-hydroxysteroid dehydrogenase in common epithelial ovarian tumors.

Type 1 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is an estrogen-metabolizing enzyme that catalyzes the conversion of estrone to the more biologically potent estradiol. We examined the immunolocalization of 17 beta-HSD in five specimens of normal human ovary and in 51 specimens of common epithelial tumors of the ovary to study the expression of 17 beta-HSD in these ovarian neoplasms. 17 beta-HSD immunoreactivity was detected in granulosa cells of dominant preantral follicles but not in the surface epithelium of the normal cycling human ovary. In 12 patients, the enzyme was not expressed in tumor cells of benign cystadenoma. 17 beta-HSD was immunolocalized in the cytoplasm of four specimens (50%) of eight of tumors of low malignant potential and in 20 specimens (67%) of 30 of invasive carcinoma. 17 beta-HSD immunoreactivity was also observed in nonluteinized stromal cells of mucinous tumors (two adenomas of six, three tumors of five with low malignant potential, and two of 10 invasive carcinomas) but not in other histologic types. Type 1 17 beta-HSD expression, therefore, correlated with malignant transformation of the surface epithelium of the human ovary, supporting a possible role in its progression by increasing in situ estradiol concentration.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

Immunohistochemical study of DNA topoisomerase II in human gastric disorders.

Topoisomerase II (topo II) separates chromosomes at the end of mitosis and is also the target for various chemotherapeutic agents. Expression of this enzyme has been demonstrated to increase rapidly at the end of the S to G2/M phase and decrease after the completion of mitosis. We immunolocalized topo II in specimens of both normal and neoplastic human gastric mucosas to evaluate expression of this enzyme. Three different antibodies were used for the immunostaining of topo II (anti-topo II alpha isoform, anti-topo II beta isoform and anti-topo II alpha and -beta isoforms). There were no significant differences in topo II labeling index (LI) between frozen and paraffin-embedded tissue sections obtained from the same cases. Topo II LI was significantly correlated with Ki67 LI in all of the specimens examined. The area of cells positive for Topo II was much narrower than that of Ki67 in the normal gastric glands, and the pattern of Topo II immunolocalization in both adenomas and adenocarcinomas was also essentially the same as that of Ki67. The topo II LI values (positive cells/1000 cells) for normal gastric gland, adenoma, intestinal-type adenocarcinoma, and diffuse-type adenocarcinoma were 114.7 +/- 2.2, 266.7 +/- 18.8, 277.6 +/- 19.2, and 324.5 +/- 5.3, respectively. Significant differences in topo II LI and topo II/Ki67 index were observed between normal and neoplastic mucosas (P < 0.0001) and between adenomas or intestinal-type adenocarcinoma and diffuse-type adenocarcinoma (P < 0.001 and P < 0.01, respectively). Simultaneous measurement of topo II alpha and nuclear DNA content by two-parameter flow cytometry revealed that the Jurkat cell line established from acute lymphocytic leukemia cells expressed the enzyme in cells at other than S and G2/M phases of the cell cycle whereas topo-II alpha-positive cells were predominantly observed in S and G2/M phases of the cell cycle in the cells from normal lymph nodes. These findings suggest that dys-regulation or qualitative changes of topo II alpha expression are associated with malignancy. Topo II immunostaining can thus detect proliferating cells in routinely processed tissue sections and can indicate the altered topo II alpha expression in human cancers, which may be related to the sensitivity to topo-II-targeted chemotherapeutic agents.

Adenocarcinoma↗
PubMed1996

[DNA subtraction in situ hybridization--new approaches of detecting genetic defects in surgical pathology specimens].

A novel in situ histochemical method of screening genetic alterations of human malignant cells was reported. The method is based on subtraction in situ hybridization of whole genomic DNA from a healthy volunteer or DNA extracted from non-neoplastic tissues. The method can widely examine the possible DNA defects in situ without employing specific probes employing colorimetric reaction in routinely processed surgical pathology materials, i.e. 10% formalin-fixed and paraffin embedded tissue sections. Results can be correlated with histopathological findings. In this report, we also describe the results on genetic alterations of human esophageal squamous cell carcinoma, using this DNA subtraction in situ hybridization.

Carcinoma, Squamous Cell↗
PubMed1995

Accumulation of plasma cells in atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits.

By screening a cDNA library constructed from aortic total RNA derived from Watanabe heritable hyperlipidemic (WHHL) rabbits by differential hybridization, we have obtained a cDNA encoding the kappa light chain of immunoglobulin. Northern blot analysis of total RNA prepared from aortas of WHHL and normal rabbits of various ages revealed that this light-chain mRNA accumulates gradually with age in aortas in WHHL rabbits. Northern blotting and in situ hybridization with an antisense oligonucleotide specific to rabbit immunoglobulin gamma heavy-chain mRNA also detected accumulation of this heavy-chain mRNA in advanced lesions of WHHL rabbit aortas. Moreover, immunohistochemical and electron microscopic analyses demonstrated the presence of plasma cells in the atherosclerotic lesions.

Amino Acid Sequence↗
PubMed1995

Prognostic value of epidermal growth factor receptor expression in endometrioid endometrial carcinoma.

We report here a retrospective study of epidermal growth factor receptor (EGFR) expression in 140 patients with human endometrioid endometrial carcinoma (median period of follow-up, 43.8 months; ranging from 1 to 155 months). Tumor specimens were immunohistochemically examined for the overexpression of EGFR, and the correlation among EGFR status, various clinicopathologic parameters, and prognosis was statistically evaluated. Monoclonal antibody (clone 31 G 7), which recognizes the extracellular domain of the EGFR molecule, was used for immunostaining. Ninety-four of 140 cases were immunohistochemically positive for EGFR (67.1%). The presence or absence of EGFR did not correlate with surgical stage, depth of myometrial invasion (DI), or lymph node involvement, but did correlate with histological grade and patient's age. Furthermore, patients with EGFR-positive endometrial carcinoma had a statistically significant shorter length of survival than those with EGFR-negative tumors (P = .018). This trend is more apparent among the patients more than 50 years old (P = .003). When adjusted for surgical stage, DI, and patient age, EGFR status retained prognostic value by multivariate analysis. However, when adjusted for surgical stage, histological grade, DI, and patient age, EGFR status failed to retain prognostic value by multivariate analysis. The results of this study suggest that EGFR expression is correlated with histological grade and greater invasiveness of human endometrioid endometrial carcinoma.

Carcinoma, Endometrioid↗
PubMed1995

Transcription factor adrenal 4 binding protein as a marker of adrenocortical malignancy.

Adrenal 4 binding protein (Ad4BP) is a transcription factor that regulates the expression of the steroidogenic enzymes and is expressed primarily in steroidogenic cells. We immunolocalized Ad4BP in adrenocortical carcinoma (eight cases) and various malignancies that histologically simulate an adrenocortical carcinoma to evaluate the value of Ad4BP as an immunohistochemical marker of adrenocortical carcinoma. These malignancies examined were renal cell carcinoma (20 cases), hepatocellular carcinoma (10 cases), malignant melanoma (eight cases), ovarian (six cases) and uterine (three cases) clear cell carcinoma, large cell carcinoma of the lung (five cases), and pheochromocytoma (three cases). Nuclear Ad4BP immunoreactivity was observed only in adrenocortical carcinoma cases but not in other tumors examined. Almost all of the adrenocortical carcinoma cells were immunohistochemically positive for Ad4BP including cells associated with bizarre nuclei. These results show that application of Ad4BP immunostain can contribute greatly to the differential diagnosis of adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗
PubMed1995

Adrenocortical cytopathology.

Cytopathologic smears and/or imprints of human adrenal cortex (9 cases) and its disorders were examined, including adrenocortical nodule (3 cases), adrenocortical adenoma (23 cases), carcinoma (8 cases), and renal cell carcinoma (6 cases). Immunocytochemistry directed against 3 beta-hydroxysteroid dehydrogenase and adrenal-4-binding protein (Ad4BP), a transcription factor in steroidogenesis, was also performed. There were no cytologic differences between normal adrenal and adrenocortical nodules. Large nuclei with prominent nucleoli were observed predominantly in adrenocortical neoplasms. Cellular atypia or pleomorphism and the degree of cohesiveness were unreliable criteria in differentiating between adrenocortical adenoma and carcinoma. Mitosis and necrotic materials were observed only in adrenocortical carcinoma. These cytologic findings were considered contributory, but not diagnostic when evaluating adrenocortical disorders because of marked intra-tumoral heterogeneity. There were no reliable cytologic criteria in differentiating adrenocortical and renal cell carcinoma. Immunocytochemistry of 3 beta-hydroxysteroid dehydrogenase and especially Ad4BP was demonstrated to aid greatly in the differential diagnosis between these carcinomas by identifying adrenocortical parenchymal cells.

3-Hydroxysteroid Dehydrogenases↗