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T Hachisuga

Publications and source records attributed to T Hachisuga.

At least 19 recordsLinked to original sources
PubMed2005

K-ras mutation in the endometrium of tamoxifen-treated breast cancer patients, with a comparison of tamoxifen and toremifene.

The putative presence of a mutation in codon 12 of the K-ras gene was investigated in the endometrium of tamoxifen (TAM) and toremifene (TOR)-treated breast cancer patients. DNA was extracted from fresh cytologic samples of the endometrium in 86 TAM and 21 TOR-treated breast cancer patients. Mutations were detected by enriched PCR and an enzyme-linked mini-sequence assay (ELMA). K-ras mutation was found in 35 TAM-treated endometrial samples, and in only one TOR-treated endometrium (P<0.003). In 24 premenopausal patients, K-ras mutation was found in seven (43.8%) of 16 patients with less than 47 months of TAM treatment, while none was found in eight patients with more than 48 months of TAM treatment (P<0.03). In 62 postmenopausal-amenorrheic patients, K-ras mutation was found in three (15.8%) of 19 patients with less than 23 months of TAM treatment, while it was found in 16 (61.5%) of 26 patients with 24-47 months of TAM treatment and nine (52.9%) of 17 patients with more than 48 months of TAM treatment (P=0.002). The presence of K-ras mutation is significantly influenced by the duration of TAM treatment and menstrual status of the patients. TOR may have a lower potential genotoxicity than TAM.

Adult↗
PubMed2001

Endometrioid adenocarcinomas of the uterine corpus in women younger than 50 years of age can be divided into two distinct clinical and pathologic entities based on anatomic location.

BACKGROUND: This study used the clinicopathologic profiles of Japanese women younger than 50 years of age with endometrial carcinoma to distinguish the clinicopathologic features of carcinomas of the lower uterine segment (LUS) from those of carcinomas of the corpus mucosa proper (CMP). METHODS: Eighty-eight endometrial carcinomas in women younger than 50 years old (25.3%) were selected from our file of 348 Japanese women with endometrial carcinoma. Seventy-two were classified as carcinomas of the CMP and 16 carcinomas of the LUS. A tumor was judged to be a carcinoma of the LUS when it involved a continuous area ranging from the lower corpus to the upper cervix with or without intervention of a portion of uninvolved LUS. RESULTS: The mean ages of women with carcinomas of the CMP and LUS were 41.2 and 39.0 years, respectively. In comparison to carcinomas of the LUS, carcinomas of the CMP were more strongly associated with reproductive risk factors including parity (P = 0.01) and polycystic ovary syndrome (P = 0.02). There was no significant difference in body mass index or the incidence of diabetes mellitus and hypertension between women presenting with carcinomas of the CMP and LUS. Histologically, carcinomas of the LUS more frequently showed a high-grade endometrioid tumor (P = 0.02) with deep myometrial invasion (P < 0.01) and were less associated with endometrial hyperplasia (P < 0.01) than those of the CMP. CONCLUSIONS: Carcinomas of the LUS occurred predominantly in women younger than 50 years of age and had clinicopathologic features distinct from carcinomas of the CMP in women younger than 50 years of age.

Adenocarcinoma↗
PubMed2001

The effect of nulliparity on survival in endometrial cancer at different ages.

OBJECTIVE: Nulliparity is a major independent risk factor for endometrial cancer in Japan. We examined the effect of nulliparity on survival in endometrial cancer at different ages. METHODS: A retrospective study of 328 Japanese women with endometrial cancer was performed. The subjects were divided into two groups: a younger age group (women < 50 years) and an older age group (women >/= 50 years). Parity was analyzed for its influence on survival. RESULTS: No effect of nulliparity was observed on survival in the younger group. In the older women, nulliparity did not affect survival in 189 subjects with surgical stage I and II tumors (P < 0.27). In contrast, the cumulative 10-year survival rates associated with nulliparity, a parity of 1 or 2, and a parity of 3 or more were 7.7, 48.0, and 56.2% in 54 subjects with surgical stage III and IV tumors, respectively (P < 0.03). In these 54 subjects, the cumulative 10-year survival rates associated with < 6-month and > 7-month delays in diagnosis were 57.1 and 16.6%, respectively (P < 0.02). The prognostic impact of parity disappeared after adjustment for delay in diagnosis. Multivariate analysis including histopathological variables, parity, and delay in diagnosis showed no independent prognostic variable in the older subjects with surgical stage III and IV tumors. CONCLUSIONS: The negative effect of nulliparity on survival was observed in the older subjects with advanced-surgical-stage tumors. Delay in diagnosis contributed to the prognostic impact of nulliparity.

Adenocarcinoma, Clear Cell↗
PubMed2001

Local immune response in squamous cell carcinoma of the uterine cervix.

The role of Langerhans cells as antigen-presenting cells was examined in cervical carcinomas. Frozen samples were obtained from 34 women with stage Ib and II cervical carcinomas. Langerhans cells (CD1), T lymphocytes (CD4 and CD8), B lymphocytes (CD22), and natural killer (CD57, NK) cells were all quantitatively assessed in cervical carcinomas using immunohistochemical methods. These results were related to the MHC class I and II expression on the tumor cells. The majority of Langerhans cells were distributed among cancer cells and they were positively correlated with CD4+, NK and B cells in cervical carcinomas. This is suggestive of the presence of local immune response. The numbers of Langerhans, CD4+, CD8+ and NK cells did not significantly correlate with age at operation, lymph node metastases or depth of cervical wall invasion. The downregulation of MHC class I expression found in 8 (24%) carcinomas was not associated with the decrease in the number of immunologic cells. The upregulation of MHC class II expression found in 26 (76%) carcinomas was significantly associated with the increase in the number of Langerhans cells (p < 0.007). However, the association between the upregulation of MHC-II expression and CD4+ cells did not reach statistical significance (p < 0.07). This is probably due to a small case in this study. MHC-II-restricted immunity may partly contribute to the local immune response in stages Ib and II squamous cell carcinoma of the uterine cervix.

Adult↗
PubMed1999

The grading of lymphovascular space invasion in endometrial carcinoma.

BACKGROUND: This study was conducted to elucidate the prognostic significance of a three-grade system for lymphovascular space invasion (LVSI). METHODS: The prognostic significance of the grading of LVSI as compared with other pathologic variables was evaluated in a study of 303 Japanese women with endometrial carcinoma. The criteria for determining the grade of LVSI were as follows: none (no LVSI), mild (a focus of LVSI was recognized around a tumor), and severe (diffuse or multifocal LVSI were recognized around the tumor or in the myometrium regardless of the degree of myometrial invasion). Both univariate and multivariate regression analyses were performed. The effects of different surgical methods and adjuvant therapies on survival were also examined. RESULTS: A univariate survival analysis showed that survival significantly correlated with surgical stage, histologic grade, depth of myometrial invasion, LVSI, cervical invasion, ovarian metastasis, and tubal metastasis. Of the three grades of LVSI, survival showed the most difference between the mild and severe groups. In multivariate analysis, the highest correlation with survival was observed for LVSI (P = 0.0008). Lymph node metastasis was also significantly associated with LVSI (P = 0. 0001). The correlation between histologic variables and survival was only slightly influenced by the differences in surgical methods and adjuvant therapies. CONCLUSIONS: The grading of LVSI was found to be an important histologic prognostic variable. The severe degree of LVSI also was found to be a good indicator of lymph node metastasis. It is therefore important to evaluate the grade of LVSI based on a histologic examination of at least one cut surface of the hysterectomy specimen that macroscopically shows the deepest myometrial invasion.

Endometrial Neoplasms↗
PubMed1999

Prognostic significance of progesterone receptor immunohistochemistry for lymph node metastases in endometrial carcinoma.

OBJECTIVE: The aim of this study was to determine whether progesterone receptor (PR), estrogen receptor (ER), p53 protein, and proliferating cell nuclear antigen (PCNA) expression constitute independent prognostic factors for lymph node metastases in endometrial carcinoma using immunohistochemical techniques on hysterectomy and biopsy specimens. METHODS: We evaluated the correlation between lymph node metastases and PR/ER immunohistochemistry, p53/PCNA expression, age, tumor grade, myometrial tumor invasion, cervical involvement, and ovarian metastases in a series of 99 cases of primary endometrial carcinoma surgically staged with systemic pelvic lymphadenectomy and para-aortic lymph node biopsy. RESULTS: Lymph node metastases from endometrial carcinoma were statistically correlated with negative PR immunohistochemistry (P = 0.001), intense p53 expression (66% or more of the tumor cells stained, P = 0.003), deep myometrial tumor invasion (greater than one-half, P = 0.001), and cervical involvement (P = 0.001). Tumor grade showed borderline statistical significance for lymph node metastases (P = 0.058). On multivariate analysis, negative PR, intense p53 expression, and cervical involvement were significant prognostic variables for lymph node metastases (P = 0.0001, 0.0023, and 0.002, respectively). Immunohistochemical study indicated that the PR status on preoperative biopsy specimens and hysterectomy specimens was in good agreement, but p53 status was not. Age, ovarian metastases, ER immunohistochemistry, and PCNA expression were not significantly related to lymph node metastases. CONCLUSION: PR immunohistochemistry appeared to be the most powerful prognostic factor associated with lymph node metastases in endometrial carcinoma, independent of other clinicopathological parameters.

Adult↗
PubMed1999

Expression of steroid receptors, Ki-67, and epidermal growth factor receptor in tamoxifen-treated endometrium.

Endometrial specimens of 34 (25 premenopausal and 9 postmenopausal) breast cancer patients receiving tamoxifen were immunohistochemically examined using estrogen receptor (ER), progesterone receptor (PR), Ki-67, and epidermal growth factor receptor (EGFR) antibodies. Proliferative (n = 6), secretory (n = 9), and postmenopausal (n = 6) endometria served as controls. The ER and PR expressions of the glandular cells in tamoxifen-treated patients did not differ from those of the glandular cells in the control women regardless of menopausal status. The Ki-67 index of glandular cells in tamoxifen-induced amenorrheic women was found to be lower than that of the proliferative glandular cells in the control women (p < 0.03), whereas the Ki-67 index of glandular cells in the tamoxifen-treated postmenopausal patients was higher than that of the glandular cells in the control women (p < 0.02). No EGFR overexpression was found in the glandular cells of the tamoxifen-treated premenopausal patients, but expression of EGFR was high in glandular cells of the tamoxifen-treated postmenopausal patients associated with a high Ki-67 index. In competition with ovarian estrogen secretion, tamoxifen may have an antiestrogenic effect on the endometrium, but tamoxifen probably has an estrogenic effect in the absence of ovarian estrogen secretion. This estrogenic effect of tamoxifen may be associated with an EGFR autocrine system.

Adult↗
PubMed1998

The blood flow characteristics in borderline ovarian tumors based on both color Doppler ultrasound and histopathological analyses.

To clarify the tumor behavior in borderline ovarian tumors, we examined the characteristics of neovascularization in these tumors by using a transvaginal color Doppler ultrasound (TV-CDU). Twelve patients with borderline ovarian tumors were preoperatively evaluated for the characteristics of intratumoral blood flow by TV-CDU, using both the resistance index (RI) and pulsatility index (PI). As a control group, 100 patients with benign ovarian tumors and 31 patients with malignant ovarian tumors were also examined by TV-CDU. An intratumoral blood flow was significantly detected in both borderline (91.6%; 11/12) and malignant ovarian tumors (90.3%; 28/31), but not in benign ovarian tumors (53%; 53/100) (P < 0.01). In addition, both the mean RI and mean PI values were significantly lower in the borderline (RI; 0.45, PI; 0.67) and malignant ovarian tumors (RI; 0.39, PI; 0.58) than those in the benign ovarian tumors (RI; 0.61, PI; 1.05) (P < 0.01). In mucinous tumors, the borderline tumors showed a significantly high intratumoral vascularity (P < 0. 01) and both borderline and malignant tumors significantly demonstrated a low-resistance blood flow (P < 0.01), in comparison to those of the benign tumors. Mucinous borderline tumors of the intestinal type also tended to have a lower RI as well as a lower PI value than müllerian type. Regarding neovascularization as represented by intratumoral blood flow characteristics, this study thus suggests that a close relationship exists in the tumor behavior between borderline and malignant ovarian tumors, especially in mucinous epithelial tumors.

Adolescent↗
PubMed1997

Correlation between human papillomavirus positivity and p53 gene overexpression in adenocarcinoma of the uterine cervix.

In the pathogenesis of cervical squamous cell carcinoma, an inverse correlation between human papillomavirus (HPV) infection and mutation of the p53 anti-oncogene has been suggested. Much less is known of a possible correlation in the case of adenocarcinoma of cervix. Twenty-five cervical adenocarcinomas and 7 adenosquamous carcinomas were analyzed for presence of HPV DNA sequences and overexpression of the p53 gene. Polymerase chain reaction revealed that 11 were positive for HPV DNA (34%). Seven were positive for HPV 16 and 5 for HPV 18. A mixed infection with HPV 16 and 18 was observed in 1 case. Patients with HPV-positive carcinoma were significantly younger than those with HPV-negative carcinoma (43 +/- 13.3 years versus 57 +/- 17.4 years, P = 0.01). Immunohistochemical staining showed that p53 was overexpressed in 11 of 32 cases (34%). Overexpression of the p53 gene was found in only 1 of 11 HPV-positive cases (9%) yet was evident in 10 of 21 HPV-negative cases (48%). This inverse association was statistically significant (P < 0.05). Prognostic analysis revealed that HPV-negative adenocarcinomas had a poorer prognosis than HPV-positive cases (P < 0.01) and that tumors with p53 overexpression also had a poorer prognosis than those without such overexpression (P < 0.01). Our observations suggest that HPV-negative or p53-positive adenocarcinomas may be a biologically distinct subset with a poorer prognosis.

Adenocarcinoma↗
PubMed1997

The prognostic value of semiquantitative nuclear grading in endometrial carcinomas.

The objective of this study was to evaluate the prognostic value of a convenient nuclear grading system based on only the proportion of nuclei measuring more than 10 microm in length at the shortest axis in endometrial carcinomas. Of the 235 cases reviewed, 9 serous and 5 clear cell adenocarcinomas and 2 small cell carcinomas were eliminated, resulting in a study population of 219 cases of endometrial adenocarcinoma. The architectural grade was determined by the FIGO system. The criteria for nuclear grade were as follows: grade 1, no nucleus measuring more than 10 microm in length at the shortest axis; grade 2, nuclei measuring more than 10 microm in length at the shortest axis seen in percentages ranging between 0 and 10% of tumor cells in active areas; and grade 3, more than 10% of tumor cells in active areas with nuclei measuring more than 10 microm in length at the shortest axis. The criteria for combined grades were as follows: the tumors were graded according to the architectural grade, but high-grade nuclear abnormalities increased the grade by one for architectural grade 1 and 2 tumors. The cumulative 10-year survival rates for architectural grades 1, 2, and 3 were 92.4, 82.6, and 65.2%, respectively (chi2 = 17.9, P = 0.001). The survival rates for nuclear grades 1, 2, and 3 were 96.2, 76.1, and 70.1%, respectively (chi2 = 21.6, P < 0.001), while for combined grades 1, 2, and 3 the survival rates were 98.3, 83.2, and 65.2%, respectively (chi2 = 26.9, P < 0.001). Even when the cases were limited to the 147 stage I endometrial carcinomas examined, the prognostic value of the combined grading system was still found to be superior to that of the architectural grading system. Our observations therefore supported the FIGO recommendation for nuclear grade not only in stage I endometrial carcinomas, but also in all stages of endometrial carcinomas.

Adenocarcinoma, Clear Cell↗
PubMed1997

Small-cell carcinoma of the endometrium: an immunohistochemical and ultrastructural analysis.

Small-cell carcinoma of the endometrium is a rare neoplasm, and its aggressive behavior has been reported. We report a case of small-cell carcinoma occurring primarily in the endometrium of a 62-year-old woman with postmenopausal vaginal bleeding and lower abdominal pain. The excised uterus showed a necrotic polypoid mass and histologically displayed an endometrial small-cell carcinoma. Immuno-histochemically, the tumor cells were positive for cytokeratin, the epithelial membrane antigen, neuron-specific enolase, and chromogranin, but were negative for the leukocyte common antigen and Grimelius stain. Ultrastructural analysis revealed the presence of dense core granules in the cytoplasm of tumor cells. The patient died 2 months after surgery because of aggressive behavior of the tumor. We wish to distinguish small-cell carcinoma of the endometrium from conventional epithelial tumors of the endometrium, because of the former's distinctive histopathologic, immunohistochemical, and ultrastructural characteristics.

Carcinoma, Small Cell↗
PubMed1997

Local immune response in endometrial carcinomas.

OBJECTIVE: To determine whether Langerhans cells act as antigen-presenting cells in endometrial carcinomas and their related lesions. SAMPLES: Frozen endometrial samples were obtained from 13 women with normal menstrual cycles, 3 postmenopausal women, 11 women with hyperplasia (simple 4, complex 4 and atypical 3) and 32 women with endometrial carcinomas. MAIN OUTCOME MEASURES: Langerhans cells (CD1), T lymphocytes (CD4 and CD8), B lymphocytes (CD22), natural killer (NK) cells (CD57) and HLA-DR were all quantitatively assessed in endometrial samples using immunohistochemical method. RESULTS: The numbers of Langerhans, CD4+, CD8+ and B cells were higher in the secretory phase than in the proliferative endometrium. The CD8+ cells appeared to be more plentiful than the CD4+ cells. When compared with the proliferative endometrium, the numbers of Langerhans cells were higher in hyperplasias and carcinomas. Most of Langerhans cells were HLA-DR+, showing a strong correlation with CD4+ cells in carcinomas. This suggests that MHC class II antigen restricted lymphocytes in carcinomas are activated by HLA-DR+ Langerhans cells. However, epithelial expression of HLA-DR in carcinomas did not show on association with high numbers of Langerhans and CD4+ cells. No correlation was observed between Langerhans cells and clinicopathologic features of carcinomas. In contrast, the number of NK cells significantly decreased in noninvasive carcinomas but increased in Grade 3 tumours. CONCLUSION: Based on the above findings, Langerhans cells are considered to act as antigen-presenting cells in carcinomas, but it was not shown that they were activated by epithelial expression of HLA-DR in carcinomas.

B-Lymphocytes↗
PubMed1997

Local immune response in infertile patients with minimal endometriosis.

OBJECTIVE: To evaluate the role of local immunity in women with minimal endometriosis. METHODS: Uterine endometrium and endometrial implants were obtained simultaneously from 30 infertile women with minimal endometriosis and examined immunohistochemically using antibodies of T cell, B cell, macrophage, Langerhans cell, immunoglobulin (Ig)G, and complement (C) 3d. Serum IgG, IgA, IgM, C3, C4, antinuclear antibody and anti-DNA antibody were also examined in 24 of the women. Data from uterine endometrium and serum were compared with 10 fertile women without endometriosis as a control. RESULTS: Microscopic examination revealed that the endometrial implants were divided into two groups: group 1 (n = 13) showed lymphocytic infiltration in the endometrial implants and group 2 (n = 17) showed no or slight lymphocytic infiltration. The endometrial implants of group 1 showed significantly more dense T-cell infiltration than those of group 2. Other types of infiltrating cells and deposits of IgG and C3d revealed no significant differences between groups 1 and 2. The immunohistochemical examination of the uterine endometrium and the serum data revealed no significant differences among all three groups. Cumulative pregnancy rates showed no significant difference between groups 1 and 2. CONCLUSION: The difference of local immune response in endometrial implants did not affect systemic immunity.

Adult↗
PubMed1996

Endometrial carcinoma associated with hyperplasia.

The aim of this study was to clarify the relationship of endometrial hyperplasia to endometrial carcinoma. From 1979 through 1990, 115 cases of stage I-IV endometrial carcinomas treated initially by hysterectomy were reviewed histologically. Forty-two of 115 (36.3%) patients had hyperplasia in the endometrium adjacent to the carcinoma. Women with both endometrial carcinoma and hyperplasia were significantly younger than those with carcinoma without hyperplasia (P < 0.05). In a comparison of patients with carcinoma without hyperplasia, those with hyperplasia were better differentiated (P = 0.0072), and lacked deep myometrial invasion (P < 0.0001), cervical involvement (P = 0.0192), lymph-vascular space invasion (P = 0.0102), and para-aortic lymph node metastases (P = 0.0434). The presence of endometrial metaplasia (P = 0.0001). The estimated 5-year survival rates for patients with carcinoma with hyperplasia and those with carcinoma without hyperplasia were 96.55 and 73.33%, respectively (P = 0.0016). In endometrial carcinomas, the presence of endometrial hyperplasia may demonstrate a more favorable prognosis.

Adult↗
PubMed1996

Human papilloma virus and P53 overexpression in carcinomas of the uterine cervix, lower uterine segment and endometrium.

Inactivation of the wild type p53 protein through complexing of protein synthesized by specific subtypes of human papilloma virus (HPV) or mutation in the p53 gene in considered to play an important role in cervical carcinogenesis. The association between p53 overexpression and the presence of HPV 16 and 18 DNA was assessed in 29 cervical carcinomas, 15 carcinomas of the lower uterine segment and 30 endometrial carcinomas. In 29 cervical carcinomas (21 adenocarcinomas and 8 adenosquamous carcinomas), 7 cases were positive for HPV 16 DNA while 5 were positive for HPV 18 DNA. Nine cases (31%) showed p53 overexpression. An inverse association was seen between the presence of HPV DNA and the p53 overexpression. In 15 carcinomas of the lower uterine segment, one case was positive for HPV 16 DNA while 2 were positive for HPV 18 DNA. Overexpression of p53 was seen in 8 (53%) carcinomas of the lower uterine segment. Two of 3 HPV DNA positive carcinomas of the lower uterine segment revealed p53 overexpression. HPV DNA was not detected in endometrial carcinomas and p53 overexpression was shown in 12 (40%) cases. The association between HPV DNA and p53 overexpression differs among the tumors arising in the cervix, lower uterine segment and endometrium.

Adult↗
PubMed1995

Immunohistochemical detection of p53 overexpression in formalin-fixed, paraffin-embedded sections of endometrial carcinoma.

OBJECTIVE: In the past, immunohistochemical detection of p53 has been possible only in the case of fresh-frozen tissues. However using CM1 and an enhanced method based on microwave heating and protease digestion enabled the immunohistochemical detection of p53 overexpression in formalin-fixed, paraffin-embedded sections of endometrial carcinoma, although very few positive stainings were obtained without such an enhanced treatment. To evaluate the enhancement method, a comparative study was performed on frozen materials and paraffin-embedded samples. METHODS: Fifty-three frozen materials, including normal endometrial glands, endometrial hyperplasias and carcinomas, and paraffin-embedded samples from the same patients were used in this study. PAb1801 (mouse monoclonal antibody) was used to analyse p53 overexpression in the frozen sections, while CM1 (rabbit polyclonal anti-p53 antibody) was used for the paraffin sections. RESULTS: PAb1801 and CM1 staining on normal endometriums and endometrial lesions showed a significant degree of concordance between frozen and paraffin-embedded materials. CONCLUSION: Enhanced immunodetection of p53 in paraffin-embedded tissues will provide a useful alternative to the usual fresh-tissue assay.

Carcinoma↗
PubMed1995

[The prevention of cancer chemotherapy-induced emesis with granisetron and clonazepam].

The antiemetic efficacy of a combination of granisetron and clonazepam was investigated in 39 gynecological cancer patients treated with cisplatin. Granisetron (3 mg/body/day) was administered by intravenous drip infusion before and 24 hours after anticancer drug administration, and clonazepam was taken orally twice a day. With a combination of granisetron and clonazepam, excellent efficacy was found in 87% (34/39) of the cases. Delayed emesis occurred in 38% (13/34), but the degree of nausea was mild. Clinically, antiemetic therapy with a combination of granisetron and clonazepam demonstrated superior antiemetic effects and seems to be useful for controlling nausea and vomiting associated with cancer chemotherapy.

Administration, Oral↗