Masaki Inoue

A Case-Control Study on Risk Factors for Uterine Endometrial Cancer in Japan

A case control study of 143 Japanese women with uterine endometrial cancer and 143 individually age‐matched controls was conducted to assess the risk factors for endometrial cancers in Japan. Among the characteristics studied, the following factors were significantly greater in the cases than in the controls: nulliparity (odds ratio for parity 1–3 and ≥4 versus nullipara are 0.40 and 0.02, respectively), obesity (odds ratio: 2.73), hypertension (odds ratio: 2.4), diabetes mellitus (odds ratio: 6.30), and a personal medical history of cancer (odds ratio: 3.06). The present study showed that Japanese women have the same risk factors for endometrial cancer as those reported in Western countries. The recent increase in the incidence of endometrial cancer in Japan may be largely attributed to the decrease in parity.

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.

Adenosarcomas originating from sites other than uterine endometrium

We report three cases of adenosarcomas arising from extraendometrium of the uterus: one arising from the ovary, one from the paracolpium and one from the endocervix of the uterus. Microscopically, they consisted of an admixture of benign‐appearing epithelial and mesenchymal components with hypercellularity and minimal atypia. Two of the tumors were initially misdiagnosed as endometriosis and one was diagnosed as adenofibroma. One patient had several recurrences and died 7 years after the initial laparotomy and another patient had sarcomatous overgrowth which invaded the muscular tissues of the large intestine. Thus it appears that adenosarcoma occasionally shows grave clinical behavior, despite the benign or low‐grade appearance of its microscopic features. Problems of diagnosis and management of this tumor are discussed. An aggressive therapeutic approach including wide surgical excision is recommended even in questionable cases.

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.

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.

Immunodetection of sialyl-Tn antigen in normal, hyperplastic and cancerous tissues of the uterine endometrium

The expression of sialyl-Tn antigen (STn) in normal, hyperplastic and neoplastic tissues of the uterine endometrium was examined by immunoperoxidase staining of formalin-fixed, paraffin-embedded samples using the monoclonal antibody TKH-2, directed toward the STn structure (NeuAc 2–6GalNac 1-O-serine or threonine). STn was expressed in 13 of 18 normal postovulatory endometria with an increasing staining intensity and incidence in the late secretory phase. It was consistently absent in 10 proliferative endometria. None of 5 cystic, 4 adenomatous or 12 atypical hyperplasias expressed STn, but areas of severe cytological atypia in 3 atypical hyperplasias showed faint expression. STn expression was detected in 36 of 43 adenocarcinomas. Although the extent of staining varied from a few to most of the cancer cells, general staining was observed throughout the cytoplasm of cancer cells with increased staining of the luminal surface and frequent positive staining of intraluminal mucin. Thus, it is clear that STn is selectively expressed in cancer cells and shows restricted expression in normal and hyperplastic endometrial tissues. STn may be an early marker of malignant transformation and has potential for use as a diagnostic aid in the surgical pathology of the uterine endometrium.

Altered expression of Lewis blood group and related antigens in fetal, normal adult and malignant tissues of the uterine endometrium

The expression of the Lewis blood group and its related antigens in fetal, normal adult and malignant tissues of the uterine endometrium was examined immunohistochemically using a panel of mouse monoclonal antibodies with specificities for Lewis-a (La), Sialyl Lewis-a (SLa), Lewis-b (Lb), Lewis-X (LX), Sialyl Lewis-X (SLX) and Lewis-Y (LY) antigens. La, SLa and SLX having one fucose residue were detected in a small number of fetal tissues, while Lb and LY having two fucose residues were found in most cases. In the adult endometrium, expression of Lb and LY was considerably lower than those in fetal tissues, although expression of La and SLa was not different between these two tissues. Expression of LX and SLX was pronouned in adult when compared with fetal tissues. Malignant endometrial glands expressed La, SLa, Lb and LY, extensively, while LX and SLX were expressed less than in normal tissues. Lb and LY can thus be considered oncofetal antigens, extensively expressed in fetal and malignant tissues but not in normal adult tissues. Expression of Lb and LY was greater than that of La and SLA in carcinoma; an increase in the activity of fucose transferase might be associated with malignant transformation in the uterine endometrium.

The use of serum TA-4 in monitoring patients with malignant transformation of ovarian mature cystic teratoma

The development of cancer in mature cystic teratomas of the ovary is rare and sometimes difficult to detect because of sampling errors. Six cases of squamous cell carcinoma arising in ovarian mature cystic teratomas were studied, five of which showed an elevated level of a squamous cell carcinoma‐associated antigen, TA‐4, in the sera obtained preoperatively; the preoperative determination was not performed in the sixth case. However, no elevated TA‐4 level was detected in the sera of 28 patients with mature cystic teratomas of the ovary. Moreover, serial determination of the serum TA‐4 level showed a good correlation between the clinical course and the serum TA‐4 level. Interestingly, an abnormal TA‐4 level preceded the clinical detection of recurrence by 2 months in two patients. Thus, determination of the serum TA‐4 concentration may be useful for diagnosing and monitoring patients with squamous cell carcinoma arising in mature cystic teratomas of the ovary.

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.