Gaiko Ueda

Expression of blood group Antigens A, B, H, Lewis-a, and Lewis-b in fetal, normal, and malignant tissues of the uterine endometrium

Fetal, normal adult, and malignant tissues of the uterine endometrium were examined by immunoperoxidase staining for the blood group antigens (BGA) A, B, H, Lewis‐a, and Lewis‐b. Antigens A, B, and H compatible with the ABO status of fetuses were detected in 20 of the 22 fetal tissues that were examined. Lewis‐b immunoreactivity was also found in 21 fetuses, and Lewis‐a was present in a third of the cases. In adult endometrium the expression of BGA H and Lewis‐b was considerably lower than in fetal tissues. Malignant endometrial glands extensively reexpressed H and Lewis‐b regardless of ABO status. BGA A and B were neither absent nor accumulated in cancer tissues. Thus, H and Lewis‐b can be considered as oncofetal antigens since they were frequently expressed in fetal and cancer tissues, but not in normal adult tissues. The increased expression of Lewis‐a antigen might be associated with malignant transformation as it was observed only in malignant tissues. However, the functional significance of alterations in BGA expression that may be associated with oncogenesis remains to be investigated.

Argyrophil Small Cell Carcinomas of the Uterine Cervix

SummaryThirteen cases of argyrophil small cell carcinomas of the cervix were reviewed. Seven of nine patients, who have been followed up for more than 5 years, died. These tumors were found to be aggressive in their behavior. Immunohistochemical studies to localize several peptide hormones were positive for gastrin in two of five cases.

Clonal analysis and mutations in the PTEN and the K-ras genes in endometrial hyperplasia.

The patterns of X chromosome inactivation and mutations of PTEN and K-ras were evaluated in cases of endometrial hyperplasia to determine the presence of potentially premalignant neoplastic versus polyclonal benign cell populations. Endometrial glandular epithelial cells were collected by laser capture microdissection, and genomic DNAs were extracted. Following treatment with the methylation sensitive restriction endonuclease Hha I, polymerase chain reaction amplification was performed targeting a highly polymorphic short tandem repeat of the human androgen receptor gene (HUMARA). PTEN and K-ras gene mutations were evaluated by analysis of single-strand conformation polymorphism. Two pathologists performed histologic diagnosis of the lesions independently. Monoclonal composition was demonstrated in 13 of 15 (87%) endometrial hyperplasias with atypia and 17 of 31 (55%) complex hyperplasias without atypia. Cytological atypia is significantly associated with the clonal status of the endometrial hyperplasia (13/15 vs 17/31, P = 0.049). In contrast, all 14 normal endometrial tissue samples were polyclonal. PTEN gene mutations were detected in 4 of 13 (30%) monoclonal endometrial hyperplasias with atypia and 2 of 17 (12%) monoclonal endometrial hyperplasias without atypia but were not detected in polyclonal endometrial hyperplasias, with or without atypia. K-ras gene mutations were present in 3 of 13 (23%) monoclonal endometrial hyperplasias with atypia but not in 2 cases of polyclonal endometrial hyperplasia with atypia or in 26 cases of endometrial hyperplasia without atypia. K-ras mutation is thus significantly more frequently found in endometrial hyperplasias with atypia than those without atypia (3/15 vs 0/31, P = 0.030). This study indicates that most cases of endometrial hyperplasia with atypia and a high proportion of cases of endometrial hyperplasias without atypia originate from a single progenitor cell, possibly as a result of genetic alterations, rather than as a result of benign reactive processes.

Clinical, histochemical, and biochemical studies of an ovarian dysgerminoma with trophoblasts and Leydig cells

Abstract A rare case of germ cell tumor with hormonal activities occurring in a 6-year-old girl of normal female karyotype is reported. Urinary levels of estrogens, pregnanediol, and 17-ketosteroids, especially etiocholanolone and androsterone, were significantly elevated, but that of 17-hydroxycorticosteroids was not. Human chorionic gonadotropin (HCG) titer was also high. At operation, a solid tumor was found in the right ovary. The tumor was predominantly composed of dysgerminoma cells and admixed with the syncytiotrophoblast cells, which were proved to have HCG and monoamine oxidase activity, and with the eosinophilic cells which were similar to Leydig cells in places. The steroid biosynthetic studies in vitro revealed the presence of 17-hydroxylase and 17,20-desmolase in addition to 3β-ol-dehydrogenase and aromatizing enzyme in the tumor tissue, confirming the admixture of hormonally active cells other than trophoblasts. Although further studies are needed, a new entity of germ cell tumor was suggested by the present tumor.

The clinical value of tissue polypeptide antigen in patients with gynecologic tumors

Tissue polypeptide antigen (TPA) was measured by radioimmunoassay in sera from patients with various gynecologic tumors: 64 uterine myomas, 129 cervical cancers, 31 endometrial cancers, and 173 ovarian tumors (89 benign, 18 low‐grade malignant (LGM) and 66 malignant tumors). Among the cervical cancer patients, the incidence of elevated TPA levels increased with stage of disease from 12% in the preinvasive stage to 67% in the advanced stage. Similarly, the TPA values were elevated in 35% of the endometrial cancer patients. Among the patients with ovarian malignancies, serum TPA was elevated in the following order: LGM cases (33%), Stage I (44%), and advanced (88%). Serum TPA values varied directly with the stage and malignancy of disease, and also correlated with the effect of treatment. However, serum TPA was elevated in 22% of the patients with uterine myoma and in 12% of those with ovarian benign tumors. The current observations demonstrate that the lack of tumor specificity of TPA limits its diagnostic value in gynecologic malignancies, but that serial measurements of this antigen appear to be useful for the evaluation of therapy and monitoring of patients.

Immunohistochemical demonstration of neuron-specific enolase in gynecologic malignant tumors

Gynecologic malignant tumors were studied by the immunoperoxidase method for neuron‐specific enolase (NSE). They included 22 argyrophil cell carcinomas of the endometrium, 6 argyrophil small cell carcinomas of the cervix, 21 argyrophil cell adenocarcinomas of the ovary (endometrioid type, 10; mucinous type, 11) and 3 ovarian carcinoids (strumal type, 2; insular type, 1). NSE was demonstrated in all cases of argyrophil small cell carcinomas of the cervix and ovarian carcinoids. On the other hand, NSE was positive only in four cases of endometrial carcinomas with argyrophil cells. Argyrophil cell adenocarcinomas of the cervix and the ovary were immunohistochemically negative for NSE. The current results suggest that argyrophil small cell carcinoma of the cervix, ovarian carcinoid, and some endometrial argyrophil cell carcinomas are related to APUDoma.

A clinicopathologic study of endometrial carcinomas with argyrophil cells.

Abstract Of 41 endometrial carcinomas examined with Grimelius staining, 9 tumors were found to be composed predominantly or partially of argyrophil cells. They were 4 well-differentiated adenocarcinomas, 4 moderately differentiated adenocarcinomas, and 1 adenosquamous carcinoma. Argyrophil granules were found mainly in the apical portion and sometimes in the entire cytoplasm of glandular tumor cells in the well- and moderately differentiated adenocarcinomas. In the adenosquamous carcinoma, argyrophil granules were located in the squamous cells as well as in the grandular cells. The distribution of argyrophil granules was in parallel with that of secretory granules identified by electron microscopy. A clinicopathologic study of these 9 cases revealed that the patients with endometrial argyrophil cell carcinoma tended to be associated more frequently with obesity, hypertension, and diabetes mellitus than the patients with usual endometrial carcinoma.

Immunohistochemical Demonstration of Tumor Antigen Ta-4 in Gynecologic Tumors

Tumor antigen TA-4, raised against human cervical squamous cell carcinoma, was studied by an immunoperoxidase method in various gynecologic tumors. TA-4 was detected invariably in normal differentiated cervical squamous cells. It was also found infrequently in normal glandular cells of the cervix, but not in the endometrium. In squamous cell carcinomas of the cervix, TA-4 was positive in the differentiated cells regardless of invasiveness or histological type. It was demonstrated in some adenocarcinomas of the cervix, and less frequently in those of the endometrium. In ovarian tumors, TA-4 was localized occasionally in a variable number of glandular tumor cells of serous, mucinous, endometrioid, and clear cell carcinomas. Only a few transitional cells contained TA-4 in a Brenner tumor. Squamous components of ovarian tumors, both benign and malignant, were frequently positive for TA-4.

Strumal carcinoid of the ovary: histological, ultrastructural, and immunohistological studies with anti-human thyroglobulin.

Abstract A strumal carcinoid arising in a benign cystic teratoma of the right ovary was reported in a 40-year-old woman. The solid tumor was histologically a trabecular carcinoid tumor associated intimately with thyroid follicle-like structures. By electron microscopy, spherical dense core secretory granules were found in the cytoplasm of tumor cells. Final diagnosis of strumal carcinoid, however, was established in the present tumor by the immunohistological confirmation of thyroid tissue with anti-human thyroglobulin.

Immunohistochemical demonstration of peptide hormones in endometrial carcinomas.

Sixty‐eight endometrial carcinomas were examined histochemically and immunohistochemically for the presence of amine‐containing or neurohormonal peptide‐containing cells, particularly in relation to argyrophil cells. Argyrophil cells, detected in 43 of the 68 endometrial carcinomas by the Grimelius method, were subgrouped into two types according to the distribution of argyrophil granules and the shape of the tumor cells. Type I was found in 7 tumors and type II in 39; 3 tumors contained both cell types. The argyrophilia of type II cells was diminished in varying degrees in some tumors by diastase digestion, although it was unchanged in type I argyrophil cells. Indoleamine was detected by the formaldehyde‐induced fluorescence method in type I argyrophil cells of four carcinomas. Immunohistochemically, somatostatin‐reactive cells were found in two well‐differentiated adenocarcinomas with argyrophilia; many of these cells corresponded to some of the type I argyrophil cells, although some were nonargyrophilic. Two adenosquamous cell carcinomas with type II argyrophil cells also contained cells that were immunoreactive with antisera against gastrin; however, they were nonargyrophilic.