Asako Inagaki

Tyrosine hydroxylase indicates cell differentiation of catecholamine biosynthesis in neuroendocrine tumors

The intracellular localization of tyrosine hydroxylase (TH), which is the rate limiting enzyme in catecholamine (CA) biosynthesis, and its activity in various adrenal and other neuroendocrine tumors was studied. TH was strongly localized in adrenal medulla, pheochromocytoma, and paraganglioma, but was scatteredly expressed in neuroblastoma. TH was not detected in adrenocortical tumors, ganglioneuroma, and other neuroendocrine tumors. Neuron specific enolase (NSE) was found in all neuroendocrine tumors, but Grimelius staining showed only the secreting granules of the tumor cells. TH activity was significantly high in pheochromocytoma and paraganglioma as compared with that in normal adrenal gland, whereas TH activity was low in a neuroblastoma and was undetectable in other tumors. These findings indicate that TH correlates well with the biosynthetic function of CA in the tumor cell and, thus, both the immunostaining of TH and the measurement of its activity in adreno-medullary and related tumors may provide some information about the process of cell differentiation in these tumors.

Cushing's syndrome induced by hypersecretion of cortisol from only one of bilateral adrenocortical tumors

A case of Cushings syndrome induced by the unilateral (right side) dominance of cortisol secretion in the face of bilateral adrenal tumors is reported. The adrenal tumor resected on the right side was a so-called black adenoma and histologically without any findings of nodular hyperplasia. After resection of the adrenal adenoma, no findings of cortisol hypersecretion from the remaining adrenal tumor on the left side were observed until the present, suggesting that the tumor of the left adrenal gland is a nonfunctioning adenoma. These data imply that the adrenal adenomas have primarily developed from the adrenal gland itself, rather than from micronodular hyperplasia by corticotropin stimulation, and that one of these tumors produces excess hormones initially by corticotropin stimulation, but the other remains in cell proliferation.

The Relation between Superoxide Dismutase in Cancer Tissue and Clinico-pathological Features in Breast Cancer.

The localization of Cu/Zn- and Mn-superoxide dismutase (SOD) in breast cancer tissue (12 papillotubular carcinomas, 21 solid-tubular carcinomas, 16 scirrhous carcinomas, 1 medullary carcinoma, 1 secreting carcinoma, 1 lobular carcinoma, 1 Paget’s disease) was investigated via an immunohistochemical technique using antihuman Cu/Zn- and Mn-SOD antibodies in 10% formalin fixed-paraffin embedded thin sections. Both SODs stained strongly in the normal breast gland, but not clearly in many cancer tissues. Furthermore, Cu/Zn-SOD stained more strongly in well differentiated tubular carcinomas than in poorly differentiated tubular carcinomas. It tended to stain less in tumors which recurred or had a poor outcome, and in tumors with a diploid pattern on DNA flow cytometry. Mn-SOD staining was similar to that of Cu/Zn-SOD, but no significant differences among subgroups was found, since the incidence of positively staining tumors was too small in all groups. The intensity of SOD staining seems to change in relation to cell proliferation and differentiation in breast carcinoma, and may be a prognostic indicator, since SOD decreased in poorly differentiated carcinoma and in tumors which developed distant metastasis. Thus, the localization of SOD in breast cancer tissue can provide useful information for cancer treatment.

Cushing's syndrome with cortisol hypersecretion from one of bilateral adrenocortical adenomas: Report of a case

We report herein the case of a 40-year-old man with Cushings syndrome, diagnosed by clinical manifestations and endocrinological studies, who was found to have bilateral adrenocortical adenomas, one of which hypersecreted cortisol. The Cushings syndrome was therefore attributed to primary adrenocortical disease, and the right adrenal tumor was resected and histologically diagnosed as a so-called black adenoma. After resection of the right tumor, the left adrenal tumor showed no signs of cortisol hypersecretion for the 23 months of follow-up until the patient died of peritonitis subsequent to the rupture of a duodenal ulcer. The left adrenal tumor was examined at autopsy and found to be a cortical adenoma. These data imply that the adrenal adenomas developed primarily from the adrenal gland itself, and that one of the tumors was well differentiated and secreted excess hormones, while the other remained in cell proliferation without hypersecretion.