Biomedical subjects

I Konishi

Publications and source records attributed to I Konishi.

At least 73 records · Page 4Linked to original sources

PubMed1996

Rapid growth of an ovarian clear cell carcinoma expressing LH/hCG receptor arising from endometriosis during early pregnancy.

The complete clinical course of a case of ovarian clear cell carcinoma expressing luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor arising from endometriosis in a pregnant woman is presented. A 31-year-old woman visited a private clinic in May 1993 for screening tests for infertility. Transvaginal ultrasonography revealed no abnormal findings in the uterus or ovaries. Her menstrual cycle was regular; however, a slight luteal insufficiency was noted. She had been treated with clomiphene, and soon became pregnant. She was diagnosed to be at 5 weeks gestation in June, and at the same time, an ovarian tumor with the diameter of 5 cm was identified. Since the tumor had grown rapidly and was 9 cm in diameter 1 week later, she was referred to our hospital. When she was admitted to our hospital at 9 weeks gestation, the tumor diameter was 14 cm and we found the solid portion within the ovarian tumor. The levels of the tumor markers CA125 and CA19-9 were 106 and 51 U/ml, respectively. The crown-rump length of the fetus (24 mm) was compatible with the gestational age, and fetal heartbeat was confirmed. Under the diagnosis of ovarian carcinoma, right salpingo-oophorectomy was performed at 10 weeks of gestation. Postoperative histological examination revealed a clear cell carcinoma and endometriosis of the right ovary. Immunohistochemically, the clear cell carcinoma stained positively for LH/hCG receptors and estrogen receptors, but not progesterone receptor. No malignant cells were detected by ascitic cytology. Exploratory specimens obtained at the time of operation from the left ovary and pelvic lymph nodes exhibited no malignant cells. Based on these findings, the pregnancy was allowed to proceed, and she delivered a 3010-g male baby at 39 weeks of gestation. She had no signs of recurrence for 2 years after the operation.

Adenocarcinoma, Clear Cell↗

PubMed1996

Parametrial involvement in endometrial carcinomas: its incidence and correlation with other histological parameters.

To identify the incidence and spread pattern of parametrial involvement in endometrial carcinomas, resected parametria in 91 patients who underwent radical or modified radical hysterectomy with pelvic lymphadenectomy were histologically examined. The relationship between parametrial involvement and other histopathological features including histological type, tumor grade, depth of myometrial invasion, lymph-vascular space invasion, cervical involvement, adnexal metastasis, and lymph node metastasis was studied. Parametrial involvement was histologically demonstrated in 12 (13.2%) of the 91 cases. There were 2 patterns of spread: direct invasion of cancer cells to the parametrial connective tissue (5 cases) and lymphatic involvement within the parametrium (7 cases). According to the FIGO surgical stage, parametrial involvement was found in none (0%) of 48 patients in Stage I, 3 (11.5%) of 26 in Stage II, and 9 (52.9%) of 17 in Stage III. Among histopathological variables, the presence of parametrial involvement was significantly correlated with deep myometrial invasion and lymph-vascular space invasion in the myometrium. Multivariate analysis revealed that parametrial involvement significantly contributed to the poor prognosis in Stage II and III patients.

Aged↗

PubMed1996

Malignant plexiform tumor of the uterus: an unusual variant of epithelioid leiomyosarcoma.

A 46-year-old woman with the complaint of hypermenorrhea underwent hysterectomy for a presumed uterine myoma. The solid tumor in the myometrium was gray in color, was 4 cm in diameter, and showed hemorrhage and necrosis. Histologically, the tumor consisted of round or polygonal cells arranged in cords and nests, and its histological features closely resembled those of plexiform tumor which has been reported as a benign, epithelioid smooth muscle tumor of the uterus. In the tumor in our patient, however, mild nuclear atypia and two to three mitoses/10 high-power fields were present. Two months after the hysterectomy, the patient was found to have metastatic foci in the lumbar vertebrae and iliac bone, which contained tumor cells with the same histological features. Accordingly, the present tumor might be interpreted as a malignant plexiform tumor of the uterus, an unusual variant of epithelioid leiomyosarcoma.

Biomarkers, Tumor↗

PubMed1996

Spontaneous conception and intrauterine pregnancy in a symptomatic missed abortion of ectopic pregnancy conceived in the previous cycle.

We encountered a rare case of combined intrauterine and extrauterine pregnancy that occurred following separate spontaneous ovulations. A 33 year old woman visited our hospital with the chief complaint of abdominal pain on April 16, 1993. Her last menstruation was from March 23 for 6 days. However, the urinary human chorionic gonadotrophin (HCG) on April 19 was 1024 IU/l. Pelvic examination and ultrasonography indicated an extrauterine pregnancy, which was confirmed by laparotomy and histological identification of trophoblast cells. The urinary HCG concentration markedly decreased after the operation. However, the HCG level increased again on the fifth post-operative day, and a gestational sac (11 mm) was identified in the uterine cavity on the 11th post-operative day, indicating that this intrauterine pregnancy was established following spontaneous ovulation which occurred before the removal of the extrauterine pregnancy. This case indicates that a combined pregnancy can occur not only after simultaneous multiple ovulations but also after the separate spontaneous ovulations.

Adult↗

PubMed1996

Sclerosing peritonitis associated with luteinized thecoma of the ovary.

A unique case of bilateral luteinized thecomas of the ovary associated with sclerosing peritonitis is reported and the clinical and pathological features of this and previously reported cases are reviewed. The patient, 52 years of age, presented with abdominal distension and diarrhea. Pelvic imaging studies revealed bilateral ovarian tumors with ascites. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adhesiotomy of the small bowel were performed. Histologically, the ovarian tumor was composed of closely packed spindle to round-shaped cells, and within the spindle cell population, lutein-like cells were scattered singly or in clusters. Mitotic counts of spindle cells revealed 12 mitotic figures (MF) per 10 high-power fields (HPF) in one part of the left ovarian tumor, but other areas of the tumor showed less than 3 MF/10 HPF on average. The lesion from the resected small bowel showed prominent fibrosis, confined to the serosa with no evidence of metastasis from the ovarian tumor. The patient has undergone adhesiotomy with partial resection of the small bowel seven times since the first laparotomy because of the recurrent small bowel obstruction. The patient has survived with complications due to short bowel syndrome for 7 years after the initial surgery and so far no recurrence or metastasis of the ovarian tumor has been identified. The case reported here also supports the idea that luteinized thecoma of the ovary associated with sclerosing peritonitis may be a distinct clinicopathologic entity, in terms of the unique association and of the unique features of thecoma; that is, bilateral, hormonally inactive and apparently benign in spite of its highly mitotic activity. Additional attention should be paid to the patient's quality of life, which is often degraded by peritoneal fibrosis and small bowel obstruction.

Female↗

PubMed1996

Ascitic positive cytology and intraperitoneal metastasis in ovarian dysgerminoma.

OBJECTIVES: To verify the pattern of the spread of tumors in ovarian dysgerminoma, with special reference to intraperitoneal metastasis, and to assess clinicopathologic factors for predicting tumor extension. METHODS: Detailed data regarding ascitic cytology, macroscopical findings at surgery, and the histopathology of the surgical specimens were retrospectively reviewed in 12 patients with dysgerminoma who were treated at Kyoto University Hospital. The relationships between the tumor extension and the period of symptoms, the serum lactic dehydrogenase (LDH) level, and the operative findings also were analyzed. RESULTS: Ascitic cytology revealed a high incidence of positivity in 6 of the 10 (60%) cases examined. Extraovarian metastases were present in 4 of the 6 (67%) cases with positive cytology, and in 1 of the 4 (25%) cases with negative cytology. Intraperitoneal metastatic nodules were detected in 5 of the 12 (42%) patients either by inspection during surgery or by postsurgical histological examination. In addition, these metastatic lesions were 5 or fewer in number and 7 mm or less in diameter, except in 1 patient with widespread disease. The presence or absence of extraovarian spread of the tumor was not significantly correlated with the period of symptom, the serum LDH level, the size of the primary tumor, or the volume of the ascitic fluid. CONCLUSION: The incidence of intraperitoneal spillage and/or metastases of dysgerminoma cells might be higher than previously reported. These findings indicate the importance of ascitic cytology and careful inspection at the time of operation, as well as the rationale of postsurgical chemotherapy for dysgerminoma of an apparently early stage.

Adolescent↗

PubMed1996

Adnexal masses: transvaginal US and gadolinium-enhanced MR imaging assessment of intratumoral structure.

PURPOSE: To evaluate the accuracy of transvaginal ultrasound (US) and gadolinium-enhanced magnetic resonance (MR) imaging in the assessment of the intratumoral structure of an adnexal mass. MATERIALS AND METHODS: The population comprised 82 patients with an adnexal mass who underwent both transvaginal US and gadolinium-enhanced MR imaging and had surgical confirmation. The findings from both modalities were compared retrospectively with those of surgery. RESULTS: The sensitivity, specificity, and accuracy were 100%, 98%, and 99% with MR imaging and were 97%, 46%, and 68% with transvaginal US for the identification of solid tissue in the masses. Transvaginal US exhibited many (n = 25) false-positive results, especially in evaluation of lesions filled with blood or fatty tissue and small echogenic excrescences adherent to the wall, such as blood or fatty tissue. CONCLUSION: Both transvaginal US and gadolinium-enhanced MR imaging were highly sensitive in identification of solid components within an adnexal mass. Gadolinium-enhanced MR imaging was specific, whereas transvaginal US was nonspecific.

Adnexal Diseases↗

PubMed1996

Immunohistochemical analysis of distribution of estrogen receptors and progesterone receptors in the postmenopausal endometrium.

OBJECTIVE: To examine the expression of sex steroid receptors (ER: estrogen receptor; PR: progesterone receptor) in the postmenopausal endometrium (PMEM) and the relationship to clinical data for studying its characters. METHODS: The immunohistochemical reactivity of the PMEM was studied using monoclonal antibodies against ER and PR, in 33 postmenopausal patients. RESULTS: The endometrium was thicker in patients who were postmenopausal for 1 to 10 years (1.48 +/- 1.31 mm) than in patients who were postmenopausal for more than 10 years (0.79 +/- 0.37 mm)(p < 0.05). Among the 33 postmenopausal endometrial samples, ER positivity was found in the glands in 26 cases (78.8%) and PR positivity was detected in 18 cases (54.5%). The average age of the patients with ER positive reactivity in the glands (61.69 +/- 7.26 years) was significantly lower than that of the patients with ER negative reactivity (66.00 +/- 3.56 years)(p < 0.05). Furthermore, the endometrial thickness of the patients with ER or PR positive reactivity in the glands (1.24 +/- 1.09 mm and 1.47 +/- 1.20 mm, respectively) was significantly greater than that of the patients with ER or PR negative reactivity (0.67 +/- 0.26 mm and 0.70 +/- 0.40 mm, respectively)(p < 0.05). CONCLUSION: ER in the glands of the PMEM was determined to decrease gradually with increased aging. The presence of ER and PR in the gland cells seemed likely to determine the thickness of the PMEM.

Aged↗

PubMed1996

[A case of advanced gastric cancer showing complete disappearance of cancer cells in multiple liver metastases due to low-dose PMUE therapy].

A case of gastric cancer with liver metastasis who responded well to low-dose PMUE (CDDP, MMC, UFT, etoposide) therapy is reported. A 65-year-old man underwent distal partial gastrectomy with D2 lymph node dissection under the diagnosis of type 5 gastric cancer with multiple liver metastases. Pathological findings revealed papillary adenocarcinoma in the primary lesion and metastatic lymph nodes (No. 8a). Low-dose PMUE therapy after resection of primary lesion was effective for the liver metastases. Exacerbation was suspected, so the lesions of metastases were resected again after 2 years and 11 months postoperative course. All 4 resected lesions of metastases became old fibrous tissue with hyalinization, and 2 of 4 lesions were necrotic and surrounded by fibrous connective tissue. None of these 4 lesions included viable cancer cells. The patient has now been followed with no evidence of exacerbation. It was suggested that low-dose PMUE therapy was effective for liver metastasis of gastric cancer, especially the differentiated type.

Adenocarcinoma, Papillary↗

PubMed1995

Papillary serous carcinoma of the peritoneum in women. A clinicopathologic and immunohistochemical study.

BACKGROUND: Papillary serous carcinoma of the peritoneum (PSCP) is a primary peritoneal tumor in women that histologically resembles papillary serous carcinoma of the ovary (PSCO). Recognition of PSCP as an entity is controversial, as is the histogenesis, histopathologic differential diagnosis, and treatment. METHODS: Ten cases of PSCP retrieved from the pathology files of 4 hospitals in Kyoto and Nara, Japan, were studied clinicopathologically and immunohistochemically. RESULTS: Patient ages at presentation ranged from 40 to 74 years (median, 56 years). All patients were Asian (Japanese). None of the patients had a history of asbestos exposure. Most of the patients had abdominal swelling, ascites with positive cytology, and elevated serum CA125. At surgery, omental tumors with dissemination to the abdominal and pelvic peritoneum were found in all patients. The histology was similar to that of Grade 2 to 3 PSCO. Immunohistochemical studies using a panel of monoclonal antibodies against carbohydrates showed that Lewis Y is a good marker, in addition to S-100, placental alkaline phosphatase, CA125, and CD15 for separating PSCP from malignant mesothelioma (MM). With cytoreductive surgery and cisplatin-based combination chemotherapy and in some cases adoptive immunotherapy and radiation, a median survival of 27 months and a 5-year survival rate of 27% were attained. One patient with Grade 3 tumor has survived for more than 6 years after surgery. CONCLUSIONS: (1) Papillary serous carcinoma of the peritoneum is a definite clinicopathologic entity; (2) immunohistochemistry is a useful tool for distinguishing PSCP from MM; (3) cytoreductive surgery and cisplatin-based combination chemotherapy with other adjunct therapies such as immunotherapy and radiation may improve patient survival in PSCP.

Adult↗

PubMed1995

Altered expression of nm23-H1 and c-erbB-2 proteins have prognostic significance in adenocarcinoma but not in squamous cell carcinoma of the uterine cervix.

BACKGROUND: The reduced expression of nm23-H1 protein and/or overexpression of c-erbB-2 protein reportedly is associated with a high incidence of lymphatic metastasis or poor prognosis of the patient in a variety of human malignant tumors. METHODS: The expression patterns of nm23-H1 and c-erbB-2 proteins were analyzed by immunohistochemical staining using formalin fixed, paraffin embedded sections of 88 cases of invasive carcinoma (39 matched pairs of adenocarcinoma and squamous cell carcinoma, 8 cases of adenosquamous carcinoma, and 2 cases of undifferentiated carcinoma) and 31 cases of preinvasive lesions of the uterine cervix. RESULTS: Expression of nm23-H1 was detected in 46% of adenocarcinoma and in 36% of squamous cell carcinoma of the uterine cervix, whereas c-erbB-2 expression was evident in 49% and 38%, respectively. Negative expression of nm23-H1, positive expression of c-erbB-2, and a combined nm23-H1-negative and c-erbB-2-positive expression were associated with a high incidence of lymph node involvement (P = 0.36, P = 0.0015, P = 0.0055, respectively) and with poor prognosis of patients (P = 0.034, P = 0.014, P = 0.00008, respectively) with adenocarcinoma of the uterine cervix, but not in those with squamous cell carcinoma. Multivariate analysis using the Cox's proportional hazard model also revealed that these three factors significantly contributed to the prognosis of patients with cervical adenocarcinoma. CONCLUSIONS: Reduced expression of the nm23-H1 protein, increased expression of the c-erbB-2 protein, and a combined nm23-H1-negative and c-erbB-2-positive expression have prognostic significance in patients with adenocarcinoma, whereas they may not be associated with the prognosis of squamous cell carcinoma of the uterine cervix, nm23-H1 and c-erbB-2 proteins may have different functions according to the subtype of cervical carcinoma.

Adenocarcinoma↗

PubMed1995

Peritoneal papillary serous carcinoma arising in an infertile woman during ovulation-induction therapy: immunohistochemical expression of LH/hCG receptors.

A case of peritoneal papillary serous carcinoma arising in an infertile patient during ovulation-induction therapy is presented. A 34-year-old woman with past history of ovulation-induction therapy for infertility again received fertility drugs. During the use of gonadotropic hormones, massive ascites developed and an exploratory laparotomy revealed serous papillary carcinoma on the surface of bilateral ovaries, pelvic peritoneum, and omentum. Immunohistochemical analysis showed the tumor cells to be positive for luteinizing hormone/human chorionic gonadotropin receptors and negative for sex steroid receptors. A possible relationship between the use of gonadotropic hormones and cancer development is discussed.

Adult↗

PubMed1995

Minimal deviation adenocarcinoma of endometrioid type may arise in the isthmus: clinicopathological and immunohistochemical study of two cases.

Clinicopathological and immunohistochemical features of minimal deviation adenocarcinoma (MDA) of endometrioid type which may have arisen in the isthmus are presented. Hysterectomy specimens from two women, one 39 years of age and the other 64 years of age, showed the presence of endometrioid-type adenocarcinoma with minimal atypia and without back-to-back arrangement of the glands, which was consistent with a histological diagnosis of endometrioid MDA. However, the tumorous glands were most abundant in the isthmus, and extensively infiltrated into the cervical stroma, vagina, parametrium, and corpus in one case, and the tumor was confined to the isthmus in the other. Immunohistochemically, the tumorous glands were CEA-positive and vimentin-negative in both cases. p53 protein expression was found in one case. Histogenetic origin of MDA of endometrioid type is discussed.

Adult↗

PubMed1995

Immunohistochemical analysis of p53 protein and 72 kDa heat shock protein (HSP72) expression in ovarian carcinomas. Correlation with clinicopathology and sex steroid receptor status.

Mutations of the tumour suppressor p53 gene have been reported in a variety of human malignant tumours, and are frequently associated with overexpression of p53 protein. To examine the significance of p53 gene alteration in malignant epithelial tumours of the ovary, we studied the immunohistochemical reactivity with a monoclonal antibody against p53 (PAb 1801) in 6 ovarian tumours of low malignant potential (LMP) and 32 ovarian carcinomas. The existence of any correlation of p53 overexpression with the clinicopathological features and with the immunohistochemical expression of 72 kDa heat shock protein (HSP72) and sex steroid receptors (oestrogen receptors; ER, progesterone receptors; PR) was also analysed. Expression of p53 was found in 2 of the 6 (33.3%) LMP tumours and in 15 of the 32 (46.9%) carcinomas. Strong expression of HSP72 was observed in 11 of the 17 (64.7%) p53-positive tumours, but only in 2 of the 21 (9.5%) p53-negative ones. Histologically, p53-positivity was observed in 7 of the 10 (70%) serous carcinomas, 4 of the 6 (66.7%) mucinous, 4 of the 10 (40%) endometrioid, and none of the 4 clear cell and 2 transitional cell carcinomas. Distribution of p53-positive cells in the tumour sections was homogenous in serous tumours, but heterogenous in mucinous lesions. All of the 4 carcinomas arising in endometriotic cysts were p53-negative. These differences support the thesis of heterogeneity in ovarian carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Mutation of the nm23 gene, loss of heterozygosity at the nm23 locus and K-ras mutation in ovarian carcinoma: correlation with tumour progression and nm23 gene expression.

Alteration of expression levels of the nm23 genes has previously been correlated with metastatic status of ovarian epithelial carcinoma. To elucidate the relevance of the qualitative changes of the nm23 genes to progression of ovarian carcinoma and/or to nm23 expression levels of the tumour, 41 samples of epithelial ovarian tumours [three benign, three low malignant potential (LMP), and 35 frankly malignant tumours] were studied for mutation of the nm23-H1 and the nm23-H2 genes using single-strand conformational polymorphism (SSCP) analysis. In addition, loss of heterozygosity (LOH) at the nm23 locus on chromosome 17q was studied by CA repeat polymorphism analysis. Mutation of the K-ras gene was also analysed in the same specimens. A novel mutation of the nm23 gene was found in one case of stage III serous carcinoma without lymph model metastases. Sequencing of the subcloned mutant cDNA revealed a missense mutation from TGG to CGG at codon 133 of the nm23-H2 gene, resulting in a change from Trp to Arg. LOH at the nm23 locus was detected in 5 of 23 (21.7%) informative cases of ovarian carcinoma. Mutation of the K-ras gene was detected in 2 of 35 (5.7%) carcinomas at codons 12 and 13 respectively. There was no correlation between clinical stage or metastatic status of ovarian carcinoma and nm23 mutation, LOH at the nm23 locus or K-ras mutation. The expression levels of both the nm23-H1 and the nm23-H2 genes were lower in the tumour with nm23-H2 mutation and higher in those with K-ras mutation. This suggests that mutation of the nm23 genes and the K-ras gene affects carcinogenesis or progression of ovarian carcinoma by modulating expression of the nm23 genes.

Adult↗

PubMed1995

Immunohistochemical localization of heat shock proteins HSP70 and HSP90 in the human endometrium: correlation with sex steroid receptors and Ki-67 antigen expression.

Heat shock proteins of 72 kDa and 90 kDa (HSP70, HSP90) have been suggested to be involved in the functional modulation of sex steroid receptors. We examined the immunohistochemical localization of HSP70 and HSP90 in both the functionalis and basalis layers of normal human endometrium during various phases of the menstrual cycle. Topological correlation with localization of estrogen receptors (ER), progesterone receptors (PR), and proliferation-related Ki-67 antigen was also analyzed. HSP70 was expressed in glandular cells of the basalis but not in the cells of the functionalis during the proliferative phase. In the secretory phase, however, glandular cells of both the basalis and functionalis markedly expressed HSP70. Endometrial stromal cells at the basal layer were positive for HSP70, whereas those cells in the functional layer were negative for HSP70 throughout the menstrual cycle. The topological expression of HSP70 in glandular and stromal cells of the basalis was inversely related to Ki-67 localization. Overexpression of HSP70 in the secretory glands was associated with down-regulation of ER and PR. These findings suggest that HSP70 expression is related to either hormonal regulation of cell proliferation and/or down-regulation of sex steroid receptors. HSP90 was strongly expressed in both glandular and stromal cells during the proliferative phase of the menstrual cycle; in the secretory phase, HSP90 expression was weak in both types of the cells. However, no topological difference in HSP90 expression between the basalis and the functionalis was observed.

Adult↗

PubMed1994

Failure of down-regulation of estrogen receptors and progesterone receptors after medroxyprogesterone acetate administration for endometrial hyperplasias.

BACKGROUND: To determine the biologic difference between normal endometrium and endometrial hyperplasias, the authors assessed the expression of estrogen receptors (ER) and progesterone receptors (PR) in the subjects before and after oral administration of medroxyprogesterone acetate (MPA) (Hysron-H, Kyowa Hakko Kogyo Co., Ltd., Tokyo, Japan). METHODS: The authors studied the expression of ER and PR in pathologic conditions of the endometrium such as cystic, adenomatous, and atypical hyperplasias before and after MPA treatment, 600 mg daily, for 8-14 weeks, and compared this expression with that of normal endometrium. RESULTS: Stromal and epithelial components of the normal endometrium in the proliferative phase were positive for ER and PR. In the secretory phase and after MPA treatment, the epithelial component showed either negative or faint staining for ER and PR, but the stromal component showed positive staining for PR and negative or faint staining for ER. All hyperplasias exhibited ER and PR in the stromal and epithelial components, although the intensity of the staining was variable in atypical hyperplasias. After MPA treatment, in the epithelial component of cystic and adenomatous hyperplasias, down-regulation of PR was prominent, but many cells continued to express ER. The epithelial component usually was surrounded by PR-positive decidual cells. In atypical hyperplasia, many cells continued to express ER and PR in the epithelial component surrounded by both ER and PR positive stromal cells after MPA treatment. CONCLUSIONS: Among the pathologic conditions of the endometrium, cystic and adenomatous hyperplasias have mechanisms of down-regulation of PR but not ER in the glandular component after MPA treatment, whereas in atypical hyperplasia, down-regulation of ER and PR does not occur in the epithelial component. Compared with normal endometrium, the majority of endometrial hyperplasias have an impairment of down-regulation of ER in the epithelial component by MPA treatment, and atypical hyperplasia has an impairment of down-regulation of ER and PR. Endometrial hyperplasias seem to have an abnormality of down-regulatory mechanisms of sex steroid receptors in the epithelial component when treated with exogenous progesterone.

Adult↗

PubMed1994

Expression of metastasis-related nm23-H1 and nm23-H2 genes in ovarian carcinomas: correlation with clinicopathology, EGFR, c-erbB-2, and c-erbB-3 genes, and sex steroid receptor expression.

To verity the role of metastasis-related nm23 genes in carcinogenesis and progression of ovarian carcinoma, we analyzed the mRNA levels of the nm23 genes of both isoforms, -H1 and -H2, together with those of the epidermal growth factor receptor, the c-erbB-2, and the c-erbB-3 genes in 45 ovarian carcinomas and 5 benign cystadenomas. Expressions of nm23 gene products/nucleoside diphosphate kinases, epidermal growth factor receptor, erbB-2 protein, and sex steroid receptor status in ovarian carcinomas were also examined by immunohistochemistry. The mRNA levels of nm23-H1 and nm23-H2 were higher in carcinoma tissues compared with benign tumors (H1, P < 0.01). The mRNA levels of c-erbB-2 and c-erbB-3 were also elevated in carcinoma tissues, and there was a positive correlation between mRNA levels of the nm23-H1 and the c-erbB-2 genes (r = 0.58; P < 0.05). Correlation of immunohistochemical staining between nucleoside diphosphate kinases and erbB-2 protein was also observed in ovarian carcinoma tissues. Sex steroid receptor positivity was related to a higher expression of nucleoside diphosphate kinases. Expression levels of the nm23 genes in ovarian carcinomas were not related to either histological subtype or local extension and peritoneal dissemination. Among stage III ovarian carcinomas, however, tumors possessing lymph node metastasis showed significantly lower nm23-H1 mRNA levels than those without nodal involvement (P < 0.05). Stage IV carcinomas also exhibited lower nm23-H1 and nm23-H2 expression levels compared with other stages (P < 0.05). These results suggest that expression of the nm23 genes, especially nm23-H1, is activated, accompanied by c-erbB-2 and c-erbB-3 overexpressions, in early stages of the carcinogenic process of ovarian carcinoma and reduction of nm23-H1 expression occurs in association with lymph nodal and/or distant metastasis.

Adenocarcinoma↗