Implication of malignancy and prognosis of p27(kip1), Cyclin E, and Cdk2 expression in epithelial ovarian tumors.

OBJECTIVE: The aim of this study was to further evaluate whether the expression of p27(kip1), cyclin E, and cdk2 is related to the malignancy of ovarian tumors and whether their expressions, alone or in combination, are associated with prognosis in epithelial ovarian carcinoma. METHODS: Immunohistochemical analysis using anti-p27(kip1), anti-cyclinE, and anti-cdk2 antibodies was carried out for 103 cases consisting of benign, borderline, and malignant ovarian tumors, and Western blot analysis and cdk2 activity assay were performed in 26 fresh ovarian tumor samples. RESULTS: p27(kip1) expression was reduced in ovarian carcinomas in contrast to benign and borderline tumors. The expression of cyclin E and cdk2 gradually increased from benign to borderline to malignant tumors. Kaplan-Meier survival analysis showed that patients with p27(kip1) expression had a high overall survival rate. Patients with cyclin E overexpression had a low overall survival rate. When the combination of these proteins was analyzed, patients with the p27(kip1) (-)/cyclin E (++)/cdk2 (++) phenotype were significantly associated with the poorest overall survival. In multivariate Cox regression analysis, the combined phenotype of p27(kip1) (-)/cyclin E (++)/cdk2 (++) was independently related to poor prognosis. CONCLUSIONS: Our results suggest that loss of p27(kip1) expression and overexpression of cyclin E or cdk2 were significantly associated with malignancy in ovarian tumors. p27(kip1) and cyclin E proteins may be valuable prognostic factors for epithelial ovarian carcinoma patients. Furthermore, the combined evaluation of p27(kip1)/cyclin E/cdk2 may provide the most important prognostic implication.

Inverse expression of Cdk4 and p16 in epithelial ovarian tumors.

OBJECTIVES: The aim of this study was to elucidate the expression and the correlation of two cell cycle regulators, cdk4 and its inhibitor p16, in a series of benign, borderline, and malignant ovarian tumors and to evaluate whether their alterations correlate with clinicopathologial parameters and patients' prognosis in epithelial ovarian carcinomas. METHODS: Immunohistochemical analysis using anti-cdk4 and anti-p16 antibodies was carried out for 103 paraffin sections of ovarian tumors, and Western blot analysis and cdk4 activity assay were performed in 26 fresh ovarian tumor samples. RESULTS: The results of immunohistochemistry showed that 60.61 and 69.70% of benign, 69.57 and 56.52% of borderline, and 74.47 and 40. 43% of malignant tumors expressed cdk4 and p16, respectively, demonstrating increased cdk4 and decreased p16 expression in ovarian carcinomas. A significant inverse relationship between cdk4 and p16 expression was found. The loss of p16 expression was more correlated with G(2) and G(3) tumors in contrast with G(1) tumors. No significant correlation was observed between cdk4 expression and clinicopathological parameters. Neither cdk4 nor p16 expression has significant effects on overall survival by the Kaplan-Meier method. When the combined phenotypes of the two proteins were analyzed, patients with cdk4-positive/p16-negative expression had a reduced overall survival than other phenotypes of cdk4/p16. CONCLUSIONS: These data suggest that inverse expression of cdk4 and p16 may be involved in the development and progression of epithelial ovarian carcinomas. The combined phenotypes of cdk4 and p16 proteins could provide a useful prognostic indicator for patients with epithelial ovarian carcinoma.

Hydatidiform mole coexistent with a twin live fetus: a national collaborative study in Japan.

A national collaborative study was conducted in Japan to evaluate the clinical course and the sequelae of patients with hydatidiform mole coexistent with twin live fetus (HMTF). Seventy-two cases of HMTF were diagnosed based on gross appearance and histopathological criteria. In 18 cases, the molar parts were cytogenetically confirmed to be of androgenetic origin (complete mole). The overall incidence of persistent trophoblastic tumour (PTT) in patients with HMTF was 30.6%, and it increased to 50.0% in the 18 patients with proven androgenetic complete mole coexistent with twin live fetus (CHMTF). Among these patients, the mean gestational age at termination of pregnancy or delivery in those who developed PTT (n = 9) and those who did not (n = 9) were 20.6 and 19.4 weeks respectively. The incidence of severe maternal complications was significantly higher in patients who subsequently developed PTT (P < 0.05). The rate of subsequent development of PTT in patients with CHMTF was found to be considerably higher than in a previous study of patients with single complete mole (50 and 12.5% respectively). However, since the risk of malignancy is unchanged with advancement of gestational age, continued pregnancy may be allowed in patients with HMTF provided that severe maternal complications are controlled and fetal karyotype and development are normal.

The concurrent expression of p27(kip1) and cyclin D1 in epithelial ovarian tumors.

Mammalian cell-cycle progression is regulated by the combined action of cyclins/cyclin-dependent kinases (cdks) and cdk inhibitors. Abnormal expression as well as interaction of these proteins may result in malignant transformation of cells. To further address alterations and roles of these cell-cycle proteins in the development of epithelial ovarian carcinomas, we analyzed the expression of the p27(kip1), cyclin D1, cyclin E, and cdk2. A panel of 79 epithelial ovarian tumors was selected. Immunohistochemical staining of serial paraffin sections was performed using antibodies to p27(kip1), cyclin D1, cyclin E, and cdk2. The results showed that p27(kip1) and cyclin D1 were concurrently expressed in epithelial ovarian tumors, and the expression was down-regulated in ovarian carcinomas. There was an inverse relationship between the expression level of p27(kip1) and cyclin D1 and the histological tumor grades. On the other hand, the expression of cyclin E and cdk2 was enhanced in ovarian carcinomas. The results suggest that low expression of p27(kip1) and cyclin D1 as well as high expression of cyclin E and cdk2 promotes the development of ovarian tumors. p27(kip1) and cyclin D1 expression are negatively correlated with the malignant degree of epithelial ovarian tumors. Thus, the ovarian tumors with high p27(kip1) and cyclin D1 expression may generally have a somewhat better prognosis, while those with low p27(kip1) and cyclin D1 expression may have a worse prognosis.

Recent aspects of gestational trophoblastic disease in Japan.

The regional registration in 11 prefectures and one area covering 34% of total Japanese population started in 1974, increasing gradually to 21 prefectures and one area in 1993 covering 48.5% of total Japanese populations, by the Japan Trophoblastic Disease Committee under the auspices of Japan Society of Obstetrics and Gynecology. The results showed marked decreasing trend in incidence of molar pregnancy and choriocarcinoma in Japan. The most frequent antecedent pregnancies of choriocarcinoma has shifted from molar pregnancy in 1974 to term pregnancy in 1993. The Choriocarcinoma Risk Score Table that is in use and of practical significance, differentiating choriocarcinoma from invasive or metastatic mole by reference to simple 8 clinical items with the probability of more than 90% when compared with the histological diagnoses, is also presented.

Alleviation of cisplatin nephrotoxicity: efficacy of local intra-arterial injection concomitant with hemodialysis.

Although cis-diamminedichloroplatinum (cisplatin) is widely used in the treatment of malignant tumors, the dose administered is limited because of side effects such as nephrotoxicity. The plasma levels of non-protein-bound platinum, which can be removed by dialysis, play an important role in the antitumor effects and the appearance of side effects. Selective intra-arterial injection of cisplatin during concomitant hemodialysis (HD) was performed in patients with gynecological malignancies. At a dose of 100 mg, about three times the non-protein-bound platinum excreted in the urine during the same period was removed by HD. The area under the time-concentration curve of plasma total platinum up to 5 h after intra-arterial injection was reduced by 46%. When doses of 200 or 250 mg were administered concomitantly with HD, the maximum plasma levels were suppressed to about the same degree as when 100 mg were injected without concomitant HD. A definite reduction in the incidence of side effects was seen, and a reduction in the severity of nephrotoxicity was also observed when 100 mg were given with HD. No severe side effects were found even when 200 or 250 mg were administered with concomitant HD. The antitumor effects were not reduced or possibly potentiated, but follow-up is still of short duration. These results indicate that chemotherapy with local intra-arterial injections of cisplatin using concomitant HD not only reduces systemic side effects, in particular nephrotoxicity, but also allows for increased doses at the tumor site and can be applied in patients with renal dysfunction.

[A study on the association between glandular dysplasia and cervical squamous neoplasia in surgical specimens].

To clarify the pathogenesis of cervical adenocarcinoma, we studied the biological properties of glandular dysplasia (GD). The coexistence of squamous neoplasia with cervical adenocarcinoma has been demonstrated. We analyzed the incidence of the coexistence of GD with squamous neoplasia in this study. Materials were surgically removed uterine cervix specimens (n = 142), 52 benign disease cases, 19 squamous dysplasias of the uterine cervix, 66 squamous cell carcinomas of the uterine cervix and 5 cervical adenocarcinomas. Diagnosis of GD was based on the general rules for clinical and pathological management of uterine cervical cancer and Ng's criteria (1983). We divided GD into two types: I: endocervical type, and II: endometrioid type. These fell into subtypes, a (mild) and b (severe) based on the observed degrees of cell atypia. 1. GD coexisted in 17.3% of benign disease cases, 15.8% of squamous dysplasias, 24.2% of squamous cell carcinomas and 100% of cervical adenocarcinomas. 2. GD Ib and IIb were not found in any of the benign disease cases, but were present in 15.8% of squamous dysplasias, 13.6% of squamous cell carcinomas and 100% of cervical adenocarcinomas. If GD was defined as only Ib and IIb, GD coexisted with squamous neoplasia in this study. Our results support the theory that both cervical squamous atypia and cervical glandular atypia are derived from reserve cells.

[Clinical usefulness of GnRH agonist therapy for premenopausal women with uterine leiomyoma].

The purpose of this study was to evaluate the tumor volume reducing effect and the frequency with which menopause is induced in premenopausal women with leiomyoma uteri treated with GnRHa buserelin, 900 micrograms/day for 24 weeks. Twenty-six women, whose average age was 49.7 +/- 2.1 years (Mean +/- SD), were enrolled in this study. Uterine and myoma volume were measured by computed tomography (CT) and transvaginal sonography, respectively. Mean uterine and myoma volume had decreased by 33.7% and 39.9%, respectively at 24 weeks of GnRHa therapy. Nine patients were brought to menopause following the treatment. This rate (34.6%) is significantly higher than that of the age matched control group (11.8%), at eighteen months' observation without GnRHa treatment. We conclude that GnRHa treatment for premenopausal women with uterine leiomyoma causes not only temporary ovarian suppression but also has a strong tendency to induce menopause.

[Results of radiotherapy for stage III uterine cervical carcinomas and preliminary study of combined radiotherapy and transarterial infusion chemotherapy].

This is a retrospective analysis of 55 patients with stage III carcinoma of the uterine cervix treated with radiation from November 1984 through December 1991. Eleven of the patients were treated with radiation and transarterial infusion chemotherapy (TAI), using cis-platinum and pepleomycin. The 3- and 5-year cumulative survival rates for all patients were 61% and 58%, respectively, and the 3-year cumulative survival rate for the group with combined radiation and TAI was 47%. According to initial failure site, the locoregional recurrence rate was 36.8%, and that for para-aortic lymph node metastasis and distant metastasis was 31.6%. The failure pattern was similar between the irradiation only group and the group with combined radiation and TAI. The incidence of intestinal complications of grades 1 and 2 was 20%. Irradiation combined with TAI did not increase the incidence of complications.

[Pharmacokinetics of carboplatin after intraperitoneal administration and clinical effect in ovarian cancer].

The patients with ovarian cancer are apt to combine peritonitis carcinomatosa (PC). The effect of intraperitoneal (IP) administration of CDDP against peritonitis carcinomatosa was examined. Hydration was not necessary when CBDCA was injected, because nephrotoxicity of CBDCA was very low compared to CDDP. We studied pharmacokinetics of IP-CBCCA and its efficacy and safety. Four hundreds and fifty mg of CBDCA was dissolved in 1,000 ml of saline and administrated through the subcutaneously implanted Infuse-A-Port for 60 minutes. Complete response was 25%. The platinum concentration in the ascites (injected saline) decreased to 90.8 micrograms/ml at 2 hr after administration and to 3.8 micrograms/ml at 24 hrs, and 79.7 97.5% existed as free Pt. The concentration of serous Pt reached to 6.2 micrograms/ml at 15 min. and was kept at 6-8 micrograms/ml. and 52.4-92.7% existed as free Pt in serum. Pt was excreted to urine and reached to the peak concentration at 4 hr. Adverse effect was mainly myelotoxicity without renal toxicity and emesis. Leukocytopenia of grade 4 was 14.3%, thrombocytopenia was 25.0%. We tried IP administration to the outpatients. The doses were mainly 300 mg, but in some cases, it was escalated to 450 mg, Adverse effect of 300 mg was thrombocytopenia of grade 4 (4.8%). These results suggest that IP administration of CBDCA seemed to be a new method as locosystemic chemotherapy. We demonstrated new chemotherapeutic method to outpatients.

[MHC class I antigen expression by molar trophoblast].

It is an issue for debate why molar tissues are not rejected by an immunologically potent host, since all genes in complete moles and 2/3 genes in partial moles are considered to be paternally derived. Molar trophoblasts are in direct contact with host cells, and therefore HLA expression by these cells may hold the key to the elucidation of the immunological reaction between molar tissues and the host. It has been reported that villous trophoblasts are negative and extravillous trophoblasts are positive for HLA-A, B,C, but the expressed HLA-A,B,C molecule has been noted to lack their polymorphic determinants. We analyzed the reactivity of two monoclonal antibodies to a monomorphic determinant of HLA-A,B,C (W6/32 and Cappel anti-HLA-A,B,C) with molar trophoblasts, using three uteri containing complete moles and two containing partial moles. The reactivity was examined by an indirect immunoperoxidase method. The staining patterns were almost identical in complete moles and partial moles. Villous trophoblasts showed a negative reaction with both antibodies. On the other hand, extravillous trophoblasts exhibited intense staining for W6/32 and negative staining for Cappel anti-HLA-A,B,C, which may suggest that the expression of a constant region as well as a variant region of HLA-A,B,C molecule is incomplete.

[Cytomorphological reappraisal of choriocarcinoma cells--a proposal of a four cell pattern].

It is generally accepted that choriocarcinoma is composed of two cell types: syncytiotrophoblast (ST)-like cells and cytotrophoblast (CT)-like cells. In normal and molar pregnancy, there is another population of trophoblast in the cell column, the decidua and so forth. They are designated intermediate trophoblast (IT) and multinuclear IT. It remains to be clarified whether IT-like cells and multinuclear IT-like cells are observed in choriocarcinoma. In the present study, choriocarcinoma cells were reappraised cytomorphologically in three cases of uterine choriocarcinoma and additional three cases of metastatic choriocarcinoma. The results were as follows: 1. Choriocarcinoma cells could be classified into four cell types: ST-like cells, CT-like cells, IT-like cells and multinuclear IT-like cells. 2. IT-like cells predominated in metastatic lesions as compared with primary lesions. It seemed that choriocarcinoma shows both differentiations which take place in villous and extravillous trophoblasts of normal and molar pregnancy. IT-like cells were found to infiltrate into vessel walls, which, together with the predominance of IT-like cells in metastatic lesions, suggests that IT-like cells contribute greatly to the hematogenous metastasis in choriocarcinoma. The presence of ST-like cells, CT-like cells and multinuclear IT-like cells in metastatic lesions may indicate a germinative nature of IT-like cells.

[Establishment and characterization of ovarian pure dysgerminoma cell line secreting human chorionic gonadotropin].

A cell line, designated KURATOU, was established from a human chorionic gonadotropin (hCG)-secreting pure dysgerminoma of the ovary. The cell line comprised small cells resembling original tumor cells and large ones possessing one or a few nuclei. Population doubling time was calculated to be about 10 days. An enzyme immunoassay study of hCG in media showed that the cells produced 7-9 x 10(-6) IU/cell of hCG. Immunocytochemical studies revealed hCG in almost all of the cultured cells. The chromosomal number was distributed in triploid and the modal chromosomal number was 69. Some cells contained HLA-ABC antigens, but none contained HLA-DR antigens. The cell line was transplanted into a nude mouse and produced a tumor resembling the original tumor but with no other tumor elements.

[Analysis of trophoblast subpopulations on touch smears of chorionic villi during normal pregnancy].

Trophoblasts of normal human pregnancy are classified into syncytiotrophoblasts (STs), cytotrophoblasts (CTs) and intermediate trophoblasts (ITs) which exist in cell columns and so forth. We analyzed the trophoblast subpopulations which appear on touch smears of chorionic villi morphologically and immunohistochemically, using the uterine contents of 37 cases of induced abortion. Troma 1, a rat monoclonal antibody, was utilized as a trophoblast marker and a mouse monoclonal antibody to HLA-A,B,C was employed to discriminate ITs from CTs. The results were as follows: 1. Two sorts of cells were positive for Troma 1 and therefore were considered to be trophoblastic: Multinuclear cells of various sizes and relatively large mononuclear cells. 2. Multinuclear trophoblasts were thought to be STs because of their characteristic cytomorphology and negative reaction for HLA-A,B,C. 3. The lower the gestational age was, the more ITs were observed. 4. The cellular and nuclear size of ITs varied and their chromatin was coarsely granular with aggregates. In addition one or more marked nucleoli were noted. Consequently it would be important to take care not to misdiagnose ITs as trophoblasts of a malignant nature.

[Pharmacokinetic evidence for the renal reabsorption of CDDP].

CDDP has had a wide use and a remarkable progress in cancer chemotherapy. Among others nephrotoxicity is the principal dose-limiting factor in this drug. So that the pharmacokinetics of CDDP mainly for the kidney was investigated in 4 patients with gynecological malignancies. CDDP was administered by short-term (about 45 minutes) intra-arterial infusion at a dose of 100 mg/body. Total CDDP (T) and non-protein-bound CDDP (NPB) concentrations in plasma declined in a biphasic manner, with a half life values of 0.506, 0.551 hr in alpha phase and 102, 96 hr in beta phase respectively. Protein-bound plasma CDDP (PB) in the time concentration curve showed two peaks, at the end of infusion and at about 3-5 hours after infusion to be followed by biphasic declining, which showed similarity to the simulation curve supposing the delayed influx. Total urinary excretion rate (up to 48 hours after infusion) was 15% on the average. It was shown that there was a close relation between urinary volume of less than 3 ml/min and NPB clearance (R = 0.877). And then there was a significant difference of NPB clearances by the kidney between cases of less than 200 ng/ml of NPB plasma concentration and those over 200 ng/ml. Binding proteins at the first and the second peak were analyzed by gel filtration method. At the second peak PB was mostly detected on the albumin fraction, which was different from the first peak. The mean estimated renal reabsorption of CDDP after 3 hours following injection was about 2 mg. (ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnosis and treatment of endometrial hyperplasia].

Endometrial hyperplasia (EH) was found to coexist in 13 of 21 patients (cystic glandular hyperplasia, 13; adenomatous hyperplasia, 9) with endometrial adenocarcinoma (EC), but in only 44 of 940 patients with other than EC. In this study, blood type (A, B, H), c-myc translation products, estrogen receptor and DNA polymerase alpha were examined on endometrium of proliferative phase (EPP), EH and EC. Patient blood type products were shown in EH surrounding EC, and yet they were detected in only small portion or none of EC itself. H products were detected in EC of other than O type. c-myc translation products were shown in only a small portion of cancer cells. EPP had many ER positive cells and a few proliferating cells as they were shown by staining with anti-DNA polymerase alpha monoclonal antibody. EC can be divided into two types, one has few ER positive cells and many proliferating cells, other many ER positive cells and a few proliferating cells. In EH, the numbers of ER positive cells and DNA polymerase alpha positive cells were between those of EPP and EC. In a patient with atypical hyperplasia, high dose Medroxyprogesterone acetate (MPA) therapy induced that stratification and papillary growth of gland lining epithelia disappeared, and that cytoplasmic enlargement and vacuolation appeared. These findings were important histopathological changes in high dose MPA administration to EH and EC.

[HLA-DP and HLA-DQ antigen expression on trophoblasts of normal human pregnancy and trophoblastic diseases].

A blocking antibody in pregnant sera seems essential in understanding why a fetus can survive as a semi-allograft in an immunologically competent mother. It has been demonstrated that blocking antibody is closely related to the paternal HLA-DR antigens. However, we previously reported that HLA-DR is not expressed on any trophoblast constituting the fetal frontier at the feto-maternal interface. The present study was then undertaken to clarify whether or not trophoblasts of normal pregnancy and trophoblastic diseases express HLA-DP or HLA-DQ antigens which are closely linked to HLA-DR as a haplotype. Materials were taken from ten pregnant uteri, ranging from 8 to 22 weeks of gestation, two uteri containing complete mole and two uteri each containing gestational choriocarcinoma. Curettage specimens obtained from three cases of complete mole and two cases of partial mole were also employed. Antigen expression was examined by an indirect immunoperoxidase technique using various monoclonal antibodies. From this immunohistochemical study, neither HLA-DP nor HLA-DQ seemed to be expressed on any trophoblast of normal pregnancy and trophoblastic diseases, which, together with the negative findings of HLA-DR on trophoblasts, may suggest that blocking antibody is not generated against HLA-D locus antigens on trophoblasts.

[Morphological and immunohistochemical study on specimens of trophoblastic diseases in which the presence of a villous formation could not be established].

The histopathological discrimination between malignant trophoblastic diseases and benign trophoblastic diseases depends on the presence or absence of a villous structure. However, molar extravillous trophoblasts and cells in some placental site trophoblastic tumors (PSTT) of a benign nature, lack a villous structure. We therefore observed the morphology of trophoblastic cells which do not constitute a villous structure, including choriocarcinoma cells, and analyzed the location of placental proteins in these cells immunohistochemically. The results were as follows: 1. Molar extravillous trophoblasts were composed of large mononuclear cells and multinuclear cells. Most of them were positive for hPL and negative for hCG and SP1. 2. Choriocarcinoma consisted of cytotrophoblast-like cells, syncytiotrophoblast-like cells, large mononuclear cells and multinuclear cells resembling large mononuclear cells. HCG was noted in syncytiotrophoblast-like cells and large mononuclear cells, while hPL and SP1 were found only in syncytiotrophoblast-like cells. 3. PSTT was made up of large mononuclear cells and multinuclear cells which contained abundant hPL and very little hCG and SP1 or none at all. Molar extravillous trophoblasts were clearly distinguishable from choriocarcinoma cells in terms of their morphology and the location of placental proteins. In contrast, it seemed difficult to distinguish cells of PSTT from molar extravillous trophoblasts on a cell level.

[Endocrinological and clinico-pathologic study of granulosa-theca cell tumors of the ovary].

Nine granulosa-theca cell tumors (four pure theca cell tumors, one granulosa cell tumors, two granulosa-theca tumors and two juvenile granulosa-theca tumors) were studied endocrinologically and clinico-pathologically. The cases of juvenile granulosa-theca tumors developed precocious pseudopuberty. Three of seven other cases were re-feminized and four cases showed no hormonal manifestation clinically. The peripheral vein serum values of estradiol, progesterone, testosterone and prolactin were elevated in six of eight cases, three of four cases, four of six cases, and two of three cases, respectively. The concentration ratios between tumor harboring ovarian vein samples and peripheral vein (or opposite normal ovarian vein) samples was 2.7 to 16.9 for estrone, 8.8 to 28.6 for estradiol, 3.6 to 4.7 for progesterone, 1.6 to 6.6 for testosterone and 0.6 to 1.0 for prolactin. Estradiol was localized in both granulosa cells and theca cells, and testosterone was localized in granulosa cells in half of the cases and in theca cells in 60% of the cases. Also, testosterone was localized in all three cases in which luteinized theca cells were present. There were no cases with positive prolactin localization. These results are compatible with the concept that in granulosa-theca cell tumor, both granulosa and theca cells can produce a wide range of steroid hormones.

[Establishment and characterization of two histologically differentiated human uterine endometrial carcinoma cell lines from the same patient--a correlation between grade of morphological differentiation and HLA antigens].

The cell lines designated KKNS-I and KKNS-II were derived from the metastatic lesions in the lymph nodes of endometrial adenocarcinoma. The KKNS-I cells were small spindle or polygonal in shape and showed a jig-saw puzzle-like arrangement with a tendency to pile up. The KKNS-II cells were polygonal in shape, and larger than the KKNS-I. They appeared to be arranged like a pavement. The modal number of the two cell lines was 46 without marker chromosome. Calculating from the growth curves, the doubling times for the KKNS-I and the KKNS-II cells were 35 hours and 60 hours, respectively. The tumors obtained from the nude mouse inoculated with the KKNS-I and the KKNS-II were a poorly differentiated endometrial adenocarcinoma and a well differentiated endometrial adenocarcinoma in histology, respectively. The volume of estrogen receptor and progesterone receptor in the KKNS-II were more than that in the KKNS-I cells. HLA-ABC antigens were detected in both the cells, but HLA-DR antigens were detected in only some populations of KKNS-II cells. These data suggest a relationship between the HLA-DR antigens and the degree of differentiation of the endometrial adenocarcinoma.