Kenji Shiromizu

Analysis of E6 variants of human papillomavirus type 33, 52 and 58 in Japanese women with cervical intraepithelial neoplasia/cervical cancer in relation to their oncogenic potential.

The variation of the E6 region of human papillomavirus type 16 (HPV16) is associated with a high risk for cervical carcinogenesis. To see whether the same is the case with HPV33, 52 and 58, known to have high homology with HPV16, we analyzed the E6 sequence variation of these HPVs in 107 Japanese women with cervical intraepithelial neoplasia (CIN) or invasive cervical cancer (ICC): 20 HPV33-positive, 46 HPV52-positive and 41 HPV58-positive cases. HPV33 variants were more frequently observed in CINs I/II than in CIN III/ICCs (71% (5/7) versus 15% (2/13), P=0.02). In HPV52-positive cases, a single E6 variant was detected in 98% of the cases, whereas the prototype accounted for 98% of HPV58-positive cases. In summary, the distribution of E6 variants is different among HPV types tested, suggesting a link between E6 variation and oncogenic potential being type-specific.

Immunohistochemical characterization of undifferentiated carcinomas of the ovary

Immunohistochemical characteristics of undifferentiated carcinomas of the ovary were examined using formalin-fixed, paraffin-embedded tissues with an avidinbiotin staining approach. Eight cases were collected from the pathology files of our Institute from a total of 214 recorded malignant ovarian tumors. For immunostaining, antibodies reacting with epithelial membrane antigen (EMA), pankeratin, vimentin, CA 125, CA 19-9, carcinoembryonic antigen (CEA), α-fetoprotein (AFP), α-l-antitrypsin (AT), epidermal growth factor receptor (EGFR), c-erbB-2,bcl-2 and p53 proteins were used. All the cases examined were positive for EMA and pankeratin, specific markers for epithelial tumors, negative for the non-epithelial tumor marker, vimentin, and also positive for EGFR. Interestingly, only one case was positive for CA 125, despite it being one of the commonest reported indicators of ovarian cancer. CA 19-9 was positive in 7 cases, CEA in 5, AFP in 2, AT in 6 and c-erbB-2 protein in 4. Two cases were positive for p53 protein, and in 1 of these positive staining forbcl-2 was also observed. These results indicate that the epithelial nature is well preserved in undifferentiated ovarian carcinomas, although consistently positive reactions were not observed within the cases for some antigens. They further celarly show that a negative signal for CA 125 can not be considered to exclude the possibility of a primary ovarian tumor.

A Clinicopathological Study of Postoperative Pulmonary Metastasis of Uterine Cervical Carcinomas

Objective: To investigate the clinicopathological backgrounds and prognostic factors of uterine cervical carcinomas metastatic to the lung.

Detection of Human Papillomavirus Types 6/11, 16 and 18 in Exfoliated Cells from the Uterine Cervices of Japanese Women with and without Lesions

Human papillomavirus (HPV) infection of the uterine cervices of Japanese women with and without lesions was identified by the filter in situ hybridization method. Exfoliated cervical cells from 23 cervical papillary condylomas, 70 cervical intraepithelial neoplasia (CIN) grade I/II, 26 CIN III, 31 invasive cervical cancers and 666 cervices without evidence of disease (including 53 pregnant women) were tested for the presence of HPV types 6/11, 16 and 18. The positive rates for the detection of HPV types 6/11, 16 and 18 DNA were 47.8%, 26.1% and 8.7% in cervical condylomas, 5.7%, 15.7% and 8.6% in CIN I/II, 0, 34.6% and 0 in CIN III, 3.2%, 38.7% and 9.7% in invasive cervical cancers and 0.9%, 1.8% and 0.6% in the control cervices. These data suggest that, in Japan, HPV6/11, HPV16 and HPV18 infections are also prevalent in cervical cells with normal phenotype, and the type of HPV infection of the uterine cervix is related to the histological diagnosis.

Random nuclear p53 overexpression pattern in tamoxifen-mediated endometrial carcinoma.

SummaryIn a previous paper, we suggested that tamoxifen (TAM)-mediated endometrial carcinogenesis may not involve estrogenic pathways because of random estrogen receptor positivity among endometrial carcinomas with and without TAM treatment for breast cancer. DNA adduct formation (reported in rat liver and human endometrium) was considered to be a more plausible mechanism for TAM-mediated carcinogenesis. To examine the reported correlation between DNA adduct formation and p53, the present study examined p53 expression in the endometrial carcinomas reported in the previous study. Seven endometrial adenocarcinomas associated with long-term TAM treatment for breast carcinoma and 4 carcinomas without TAM treatment but with history of breast carcinoma were immunohistochemically investigated for nuclear p53 expression. The bcl-2 product was also examined. Diffuse and intense nuclear reactivity for p53 protein was present in only one TAM-related case. Essentially, no differences were observed in the bcl-2 staining patterns of TAM-treated and -untreated patients with cancer. Thus, p53 overexpression in endometrial carcinomas occurring in patients with breast cancer seems to be not specific for TAM-treated patients, and, if DNA adduct formation has any role in this type of endometrial carcinogenesis, it may not be related preferentially to p53 gene alteration. Further studies are needed to understand the precise mechanism(s) of the endometrial carcinogenesis.

Proliferative and apoptotic status in endometrial adenocarcinoma.

The contribution of cell proliferation and apoptosis to growth patterns in endometrial adenocarcinoma were investigated. Immunohistochemical staining was carried out by an antibody for Ki-67 proliferative antigen, Ley apoptotic antigen, and oncogene products bcl-2 and p53. Forty cases of endometrial adenocarcinoma were classified as exophytic, endophytic, and mixed exo- and endophytic in light of their vertical growth pattern, and, in each case, the carcinomatous area was divided into three layers by its vertical axis. In all but one case, no zonal distribution of the antigen expression was observed. In one case, an exophytic tumor, Ki-67 expression was intense in the surface layer and Ley expression in the deep layer was also intense, suggesting a correlation between macroscopic growth pattern and cellular growth and apoptotic potential. However, in general, zonal distribution of cell proliferation and apoptosis could not explain the growth morphology of endometrial adenocarcinoma of the uterus and it was suggested that factor(s) other than cell proliferation and apoptosis determine macroscopic growth patterns.

Cytodiagnostic problems in uterine sarcoma. Analysis according to a novel classification of tumor growth types.

OBJECTIVE To clarify the cytologic diagnostic problems of uterine sarcomas and the differential properties between pure sarcomas and carcinosarcomas. STUDY DESIGN Four leiomyosarcomas and 21 carcinosarcomas (homologous and heterologous) treated at the Saitama Cancer Center from 1991 to 2000 were analyzed macroscopically and microscopically. RESULTS Of 4 leiomyosarcomas, 3 were intramuscular, localized type, with a negative diagnosis for sarcoma. Of 21 carcinosarcomas, 7 were exophytic type with little necrosis (B-1), 5 were exophytic type with marked necrosis (B-2), 6 were exophytic type with a small sarcomatous component (B-3), and 3 were endophytic type (B-4). All endometrial smears were positive for sarcoma in B-1, whereas 5 of 14 (36%) were positive in the latter 3 types (B-2, 3 and 4). CONCLUSION In pure leiomyosarcomas, the sarcomatous portions are usually covered with normal endometrium. In carcinosarcomas, sarcomatous component is relatively limited in some cases and frequently covered with marked necrosis or carcinomatous tissue. These pathologically specific findings should make cytologic diagnosis difficult in uterine sarcomas.

Clinicopathological Study of Recurrent Uterine Cervical Squamous‐Cell Carcinoma

Objective: To improve prognoses of patients with recurrent uterine cervical squamous‐cell carcinoma.

Experience with the treatment of metastatic ovarian carcinoma.

SummaryMetastases from non-genital sites comprise about one in six of our malignant ovarian tumors. The mean age of our 24 patients with such metastases was 43.1 years and 81% had bilateral ovarian metastases. Out of the 24 patients we studied, 21 had a gastric primary. The overall survival rate was 41.7% in 6 months, 25.0% in 1 year and 12.5% in 2 years. Patients with no extraovarian metastases had a survival rate of 75.0% at 6 moths, 62.5% at 1 year and 25.0% at 2 years after operation.

Is postoperative radiotherapy or maintenance chemotherapy necessary for carcinoma of the uterine cervix

Summary. The effectiveness of postoperative radiotherapy and adjuvant chemotherapy was examined for patients with uterine cervical squamous cell carcinoma. Whole pelvis irradiation is unnecessary for patients with less than 2/3 of depth of cervical local involvement without pelvic regional lymph node metastases. Adjuvant chemotherapy with tegafur [l‐(2‐tetrahydrofuryl)‐5‐fluorouracil] (600 mg/day) has failed to improve the survival of patients with positive lymph node metastases.