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H Sasano

Publications and source records attributed to H Sasano.

At least 289 records · Page 16Linked to original sources

ACTH-independent macronodular adrenocortical hyperplasia: immunohistochemical and in situ hybridization studies of steroidogenic enzymes.

ACTH independent bilateral macronodular adrenocortical hyperplasia (AIMAH) is associated with autonomous hypercortisolism. We report six cases of AIMAH, in which immunohistochemical studies on steroidogenic enzymes (P450scc, 3 beta HSD, P450c21, P450c17, P450c11) were performed on surgically resected adrenal glands. In situ hybridization studies of P450c17 were performed in two cases in order to localize the sites of steroidogenesis. Immunoreactivity to P450scc, P450c21, and P450c11 was observed in both clear and compact cortical cells, with compact cells displaying more intense staining, as reported in Cushing's adenoma and ACTH dependent bilateral adrenocortical hyperplasia. Immunoreactivity to P450c17 was observed predominantly in small compact cells, whereas that to 3 beta HSD occurred exclusively in clear cortical cells. In situ hybridization also demonstrated that P450c17 was localized in small compact cortical cells. This differential expression of 3 beta HSD and P450c17 in clear and compact cortical cells has been observed only in AIMAH among adrenocortical disorders. This ineffective corticosteroidogenesis may contribute to the relatively low production of cortisol. AIMAH should therefore be considered as a distinct subtype of primary adrenocortical Cushing's syndrome.

3-Hydroxysteroid Dehydrogenases↗

An immunohistochemical study of the c-erbB-2 oncogene product in intraductal mucin-hypersecreting neoplasms and in ductal cell carcinomas of the pancreas.

BACKGROUND: Intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN) is a unique tumor that has a tendency to spread intraductally. The clinical outcome of IMHN generally is far better than that of pancreatic ductal cell carcinoma. Because of the presence of various cell atypia within the same tumor, it sometimes is difficult to make an accurate histopathologic diagnosis and, therefore, predict its biologic behavior. It has been shown that overexpression of c-erbB-2 protein in breast cancer with lymph node metastases is related to a poor prognosis. Overexpression of c-erbB-2 protein has been reported as an infrequent event in pancreatic ductal cell carcinoma, but little is known in the case of IMHN. METHODS: The expression of c-erbB-2 protein was immunohistochemically investigated in the formaldehyde-fixed, paraffin-embedded tissues of 17 cases of IMHN, and 14 cases of pancreatic ductal cell carcinoma (8 cases with lymph node metastasis), using polyclonal and monoclonal c-erbB-2(p185) antibodies by the avidin-biotin method. RESULTS: Both the polyclonal and monoclonal antibodies showed similar immunostaining for the c-erbB-2 product. Overexpression of the c-erbB-2 product was observed frequently in IMHN (13/17), especially in that with moderate- to high-grade cell atypia (12/12), whereas it was detected in only 1 of 14 cases of pancreatic ductal cell carcinoma (1/14). Among eight cases of pancreatic ductal cell carcinoma with lymph node metastases, overexpression of the c-erbB-2 product in metastatic lesions was detected in two, one of whose primary lesions also overexpressed the oncogene product. CONCLUSIONS: These observations suggest the genetic expression of c-erbB-2 is related to the pathogenesis of IMHN.

Adenocarcinoma, Mucinous↗

Steroidogenesis in human adrenocortical carcinoma: biochemical activities, immunohistochemistry, and in situ hybridization of steroidogenic enzymes and histopathologic study in nine cases.

To obtain a better understanding of steroid metabolism associated with adrenocortical malignancy we studied steroidogenesis in nine cases of adrenocortical carcinoma (six with Cushing's syndrome, two without clinically significant adrenocortical hormonal abnormalities, and one with primary aldosteronism) by analyzing biochemical enzyme activities (21-hydroxylase and 11 beta-hydroxylase) and by immunohistochemistry and in situ hybridization of steroidogenic enzymes in carcinoma tissues. 21-Hydroxylase activity was markedly low but 11 beta-hydroxylase activity was only moderately decreased compared with normal adrenal activity. Immunohistochemical study of steroidogenic enzymes revealed that six of the nine cases expressed all the enzymes required for cortisol or aldosterone biosynthesis. Immunoreactivity of these enzymes was predominantly observed in small carcinoma cells with compact and/or clear cytoplasm and minimum morphologic nuclear atypia. In those cases with positive steroidogenic enzymes immunohistochemical examination of serial tissue sections revealed that a number of carcinoma cells did not express all the enzymes required for the synthesis of biologically active steroids. This may account for an increased level of precursor steroid secretion associated with adrenocortical malignancy. In situ hybridization of cytochrome 17 alpha-hydroxylase demonstrated that carcinoma cells with positive hybridization signals generally were positive for immunoreactivity, but a discrepancy between mRNA and protein expression was occasionally observed. Although the conclusions derived from our current study are limited by the small number of cases, ineffective corticosteroidogenesis, characteristic of steroid metabolism in human adrenocortical carcinoma, was considered to be due to disorganized expression of steroidogenic enzymes in individual carcinoma cells.

Adolescent↗

Double immunostaining for c-erbB-2 and p53 in human stomach cancer cells.

We examined 32 cases of surgically resected stomach cancer for the immunohistochemical expression of p53 and c-erB-2 protein and correlated the findings with clinical outcome and established prognostic factors. p53 Was observed in the nuclei of tumor cells in 11 of 32 cases (33%) and c-erbB-2 immunoreactivity was observed in nine of 32 cases (27%). In eight cases both p53 and c-erbB-2 were positive; however, double immunostaining revealed that less than a third of the same tumor cells were positive for both p53 and c-erbB-2 in these cases. The immunohistochemical localization patterns of p53 and c-erbB-2 were not related to the histopathologic differentiation of the carcinoma cells. No correlation was observed between expression of p53 and/or c-erbB-2 and the clinical outcome and established prognostic factors, including clinical stage and histologic types of the tumor examined. These results indicate that abnormalities of p53 and c-erbB-2 may not play major roles in the biologic behavior of human stomach cancer and that abnormalities in p53 and c-erbB-2 do not necessarily occur simultaneously in the development of stomach cancer.

Adenocarcinoma↗

Temporal and spatial localization of steroidogenic enzymes in premenopausal human ovaries: in situ hybridization and immunohistochemical study.

In situ hybridization and immunohistochemical localization of cytochrome P450 cholesterol side-chain cleavage (P450scc), 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), cytochrome P450 17 alpha-hydroxylase (P450c17) and cytochrome P450 aromatase (P450arom) was performed in 50 morphologically normal human premenopausal ovaries, and correlated these findings with their endometrial phase. In general, mRNA expression of these enzymes examined by in situ hybridization were in good agreement with immunolocalization examined by immunohistochemistry. Expression of P450scc, 3 beta HSD and P450c17 was observed in large-sized preantral follicles, consisting of more than five layers of granulosa cells, preovulatory follicles, corpora lutea, and some degenerating corpora lutea and atretic follicles in all endometrial phases. Several follicles and/or corpora lutea positive for these enzymes were observed in the same ovary. Expression of P450arom was generally observed in only one follicle (antral or preovulatory follicle) or corpus luteum per case in mid proliferative to premenstrual phase, and was not observed in menstrual to early proliferative phase. These findings indicated that (1) expression of steroidogenic enzymes was associated with the continual human ovarian process including follicular development and atresia, and (2) especially, P450arom expression may occur only in a selected antral follicle and may have an important role in dominant follicular development.

3-Hydroxysteroid Dehydrogenases↗

Distribution of tenascin in normal cycling human ovary.

Tenascin is an extracellular matrix glycoprotein, which has been reported to be involved in parenchymal-mesenchymal interactions during morphogenesis, wound healing, and carcinogenesis. Tenascin immunolocalization was performed in 51 specimens of morphologically normal human ovaries by using a specific monoclonal antibody against purified human fibroblast tenascin. In preovulatory follicles, no significant immunoreactivity was detected. In functioning corpora lutea, immunoreactivity was present as a fine border around the periphery. In association with the involution of the corpora lutea, marked diffuse tenascin immunostaining in the intercellular space was observed. These data raise the question of whether tenascin may be involved in luteolysis and may play an important role in the ovarian cycle by regulating the involution of corpora lutea.

Cell Adhesion Molecules, Neuronal↗

Immunohistochemical comparison between anaplastic seminoma and typical seminoma.

In order to study the possible biological differences between anaplastic and typical seminoma, the following factors were studied in 11 cases of anaplastic seminoma and 15 cases of typical seminoma: mitotic activity, proliferating cell nuclear antigen (PCNA) expression, immunohistochemical analyses for cytokeratin, vimentin, placental alkaline phosphatase (PLAP), beta-human chorionic gonadotropin (beta-hCG), alpha-fetoprotein (AFP) and c-myc oncoprotein. Anaplastic seminoma was classified according to Mostofi's criteria, which is primarily based on the mitotic activity of the tumor. Mitotic activity was evaluated by both mitotic count and rate. Statistically significant correlations were observed between mitotic count and mitotic rate (R = 0.891), and between the mitotic count and PCNA labeling index (R = 0.792), in both typical and anaplastic seminomas. Immunostaining patterns for cytokeratin, vimentin, PLAP, beta-hCG, AFP and c-myc oncoprotein were not significantly different between typical and anaplastic seminoma. The present data indicated that no apparent clinicopathologic and immunohistochemical parameters discerning anaplastic seminoma from typical seminoma were present, when identifying anaplastic seminoma on the basis of high mitotic count. Anaplastic seminoma may therefore simply represent seminoma with high proliferative activity.

Adolescent↗

Immunocytochemical localization of androgen receptor with polyclonal antibody in paraffin-embedded human tissues.

We investigated the immunohistochemical localization of androgen receptor (AR) using a polyclonal antibody for 55 KD recombinant human AR in human tissues fixed with 4% paraformaldehyde solution and embedded in paraffin. Immunoreactive AR was restricted to the nuclei of various tissues. Among the well-known androgen target organs, secretory cells and basal cells of the prostate, spermatogonia, spermatocytes, Sertoli cells and Leydig cells of the testis, epithelial cells of the rete testis, fibroblasts in the whole organ, squamous cells, sweat gland and hair follicle cells of the skin, and hepatocytes of the liver were positive for AR. In addition, smooth muscle cells of the prostate, uterus, urinary bladder, gastrointestinal tract, arteries, and arterioles were strongly immunoreactive for AR. Cardiac muscle and striated muscle of psoas were positive for AR. Acinar cells, ductal cells, and myoepithelial cells of the breast, endocervical and endometrial cells of the uterus, cyto- and syncytiotrophoblast of the chorionic villi, and tubules of the kidney were also positive for AR. Most FSH, LH, and some GH endocrine cells in the anterior and posterior lobes of the pituitary gland, follicular cells of the thyroid gland, and adrenocortical cells were positive for AR. Cells immunoreactive for AR were ubiquitously distributed throughout the entire body. The present study demonstrated the diversity of androgen effects on many target tissues.

Antibodies↗

Symptomatic intradural adrenal adenoma of the spinal nerve root: report of two cases.

The second and third cases of an adrenal adenoma involving the intraspinal space, a rare location for a lesion that occurs rather commonly at a variety of extraneural sites, are reported. The first patient, a 16-year-old girl with a 3-month history of radicular pain, was found to have an intradural, extramedullary mass arising on a spinal nerve root. Its resection resulted in cure. The second patient, a 63-year-old woman with a 10-month history of low back pain with radiation to both lower extremities, had a similar mass arising from one of the nerve roots of the cauda equina. In both cases, ultrastructural examination of these demarcated, oncocytic, lipid-rich lesions demonstrated abundant smooth endoplasmic reticulum and mitochondria with tubular cristae. The presence of steroidogenic enzymes was noted on immunohistochemical examination. The literature is reviewed, as is the differential diagnosis of these rare lesions.

Adenoma↗

A case of ruptured dissecting aneurysm 5 years after pituitary microsurgical treatment of Cushing's disease: autopsy findings in the hypothalamic-pituitary-adrenal axis.

The patient was a 26-year-old man with Cushing's disease who underwent transsphenoidal microscopic surgery for a pituitary microadenoma. His postoperative course was uneventful, but he died suddenly five years after the operation. At autopsy, a ruptured dissecting aneurysm with marked atherosclerosis was observed in the aorta. In the pituitary, a small focus of adrenocorticotropic hormone (ACTH) producing adenoma, possibly residual adenoma, was detected and Crooke's degeneration was observed in the non-tumorous pituitary gland. But immunohistochemical patterns of pituitary hormones in the non-tumorous pituitary gland were normal and the adrenal cortex was unremarkable. In the hypothalamus, corticotropin-releasing hormone immunoreactivity was not detected and arginine vasopressin was sporadically positive. Considering these findings, this patient may have developed subclinical hypercortisolism due to the residual adenoma at the time of autopsy, despite clinical remission. Cushing's syndrome is considered to be a risk factor dissecting aneurysm, and in this case the metabolic changes in Cushing's disease may have influenced the development of the dissecting aneurysm. Periodic cardiovascular re-evaluations should therefore be performed when there is clinical remission of Cushing's syndrome.

Adenoma, Basophil↗

The correlation between HPV infection and cell proliferative activity in uterine cervical adenocarcinoma.

To investigate the correlation between human papillomavirus (HPV) infection and cell proliferative activity in uterine cervical adenocarcinoma, in situ hybridization of HPV DNA and immunostaining of proliferative cell nuclear antigen (PCNA) were performed on serial sections of the carcinoma. HPV 16 and 18 DNA was detected in 10 of 33 cases of cervical adenocarcinoma and adenocarcinoma in situ. PCNA was detected in 30 cases. In all 10 HPV-positive cases, PCNA was also demonstrated, and the number of PCNA-positive cells tended to be higher than that in HPV-negative cases. With 1:1 correlation between HPV and PCNA on the nuclei, the coincidence rate was 72% (p < 0.01). These results indicate that HPVs play a role in cell proliferation.

Adenocarcinoma↗

Expression of c-myc mRNA and protein in human endometrial carcinoma; simultaneous study of in situ hybridization and immunohistochemistry.

We examined the c-myc gene at both mRNA and protein levels in tumors of 10 endometrial carcinomas by simultaneous in situ hybridization and immunohistochemistry. Expression of c-myc mRNA was observed in all cases by in situ hybridization. Immunohistochemically, c-myc protein expression was also observed in all cases and immunoreactivity was recognized as nuclear staining. The site of c-myc protein expression was mostly consistent with that of c-myc mRNA expression. While there has been no clear correlation between the expression of c-myc mRNA and/or protein and prognostic parameters so far, this approach will contribute to an understanding of oncogene expression and its biological significance in human gynecological malignancies.

Endometrial Neoplasms↗

Confocal laser scanning microscopy in cytopathology.

Confocal laser scanning microscopy (CLSM) has become an exciting new instrument with rapidly expanding potential for application to the morphological examination. As an initial step of examining the possible values or potentials of CLSM observations in diagnostic pathology materials, we applied CLSM to the analysis of immunolocalization of proliferating cell nuclear antigen (PCNA), p53 and cytokeratin, and eosin and DNA fluorochrome propidium (PI) stain in cell smears obtained from 20 cases of squamous cell carcinoma of the esophagus. Superior contrasts and resolution were obtained in confocal images than in nonconfocal ones in immunocytochemistry, eosin, and PI stain. In immunocytochemistry, CLSM demonstrated subcellular localization of antigens examined, cytokeratin as coarse and fine intracytoplasmic fibers, PCNA as diffuse intranuclear localization, and p53 as heterogeneous intranuclear localization which appeared to be associated with chromatin structure. Optical sectioning of a specimen by the rejection of out-of-focus noise revealed three dimensional structure of cell clusters of squamous cell carcinoma. With eosin and PI as dyes for stain, three dimensional structures of any clusters on cell smears can be obtained. CLSM has vast potentials in the analysis of diagnostic cytology materials, including immunocytochemistry.

Antigens, Neoplasm↗

Tenascin expression in normal and abnormal human endometrium.

Tenascin has been recently characterized as an extracellular matrix glycoprotein involved in tissue interactions during fetal development and oncogenesis. In order to study the possible involvement of tenascin in epithelial growth of the human endometrium, we evaluated the expression of tenascin in 84 cases of normal, hyperplastic, or neoplastic human edometrium. The specimens were obtained by curettage and/or biopsy and analyzed by immunohistochemistry utilizing a newly developed monoclonal antibody against human tenascin. Weak periglandular immunoreactivity was observed in 50% of proliferative phase, but not in secretory endometrium. Approximately 60% of endometrial hyperplasia specimens had weak periglandular tenascin immunoreactivity, but its distribution was irregular and not necessarily correlated with degree of cell atypia. Invasive endometrial carcinomas displayed intense and diffuse staining around the carcinoma cells, in addition to thin periglandular immunoreactivity similar to that seen in hyperplasia. The intensity of tenascin staining in endometrial carcinoma was not related to the degree of tumor differentiation. These results suggest that tenascin appears as a result of interactions between neoplastic epithelium and stroma in tumor development and that diffuse and intense staining could be a stromal marker for the invading capacity of human endometrial malignancies.

Cell Adhesion Molecules, Neuronal↗

[Local recurrence of non-functioning adrenocortical carcinoma 14 years following surgical treatment: a case report].

A 76-year-old woman with a complaint of left flank pain was referred to our department for extensive examination and treatment. In 1976, she had undergone transperitoneal left adrenalectomy and nephrectomy under a diagnosis of left adrenal tumor. The surgical specimen had histologically been diagnosed as adrenocortical carcinoma. There have been no physical or endocrinological abnormalities. Computed tomogram, magnetic resonance imaging and angiogram revealed a retroperitoneal multiple hypervascular tumor with a non-homogeneous inner density. On January 16, 1991, a transperitoneal resection of the tumor with splenectomy and partial pancreatectomy was performed under a diagnosis of local recurrence of non-functioning adrenocortical carcinoma. The specimen was histopathologically diagnosed as low grade adrenocortical carcinoma based on 3 mitoses/50 hpf. From the reference study, this was thought to be the second case of late recurrence adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗

A point mutation of c-Ki-ras gene was found in human esophageal carcinoma cell lines but not in primary esophageal carcinomas.

Activation of the ras oncogene in primary human esophageal carcinomas and cell lines established from such carcinomas was analyzed using the polymerase chain reaction (PCR)-direct sequencing method. This analysis revealed a GC----AT transition at the second base in the 12th codon of the c-Ki-ras gene in TE1 and TE2 esophageal carcinoma cell lines. In contrast, no point mutation was detected in the 12th, 13th, and 61st codon of the c-Ki-ras and c-Ha-ras gene in 31 primary esophageal carcinomas including those from which TE1 and TE2 cell lines were established. These results demonstrate that while activation of the c-Ki-ras gene by point mutation occurred in a subset of esophageal carcinoma cell lines during establishment of the cell lines, the activation events are not important in the transformation of human esophageal epithelial cells.

Adenocarcinoma↗