Toshinori Kawagoe

Early cervical neoplasia confirmed by conization : Diagnostic accuracy of cytology, colposcopy and punch biopsy

OBJECTIVE To investigate the accuracy rates of cytology, colposcopy and punch biopsy in early cervical neoplasia confirmed by conization. STUDY DESIGN During the 10 years from 1984 to 1993, cold knife conization was performed on 151 patients with early cervical neoplasia proven by punch biopsy at our department. The accuracy rates of cytology, colposcopy and punch biopsy were investigated. RESULTS The accuracy rates of cytology, colposcopy and punch biopsy were 52% (78 of 151), 66% (100 of 151) and 66% (100 of 151), respectively. CONCLUSION These results suggest that a composite diagnosis with cytology, colposcopy and punch biopsy is necessary for a correct evaluation. Early cervical neoplasms are frequently seen in young women, and conservative procedures, such as conization, cryosurgery and laser vaporization, are the treatments of choice in order to preserve reproductive function. We recommend conization as the best conservative procedure, with preservation of reproductive function.

Expression of mitochondrial transcription factor A in endometrial carcinomas: clinicopathologic correlations and prognostic significance

Mitochondrial transcription factor A (mtTFA) is necessary for both transcription and maintenance of mitochondrial DNA. This study was conducted to elucidate the clinicopathologic and prognostic significance of mtTFA in patients with endometrial carcinoma. This study investigated the relationship between the immunohistochemical expression of mtTFA and various clinicopathological variables in 276 endometrial carcinomas, including 245 endometrioid adenocarcinomas and 31 nonendometrioid carcinomas (21 serous carcinomas and 10 clear cell adenocarcinomas). Both uni- and multivariate regression analyses were performed. The mtTFA labeling index of endometrioid adenocarcinomas ranged from 0% to 98%, with a median value of 32%, which was selected as the cut-off point for mtTFA expression. The mtTFA expression in endometrioid adenocarcinomas was significantly associated with the surgical stage, myometrial invasion, lymphovascular space invasion, cervical invasion, and lymph node metastasis. In contrast, no correlation between clinicopathologic variables and mtTFA expression was found in nonendometrioid carcinomas. Correlation analysis between mtTFA and p53 expression by using the Pearson test showed significant correlation in endometrioid adenocarcinomas (P = 0.007), but no significant correlation in nonendometrioid carcinomas (P = 0.947). A univariate survival analysis showed that the 10-year overall survival rate of the patients with mtTFA-positive endometrioid adenocarcinoma was significantly worse than that of patients with mtTFA-negative endometrioid adenocarcinoma (80.8% vs. 93.8%, P = 0.012). However, the multivariate analysis revealed that mtTFA expression in endometrioid adenocarcinomas was no independent prognostic factor. The positive mtTFA expression is a useful maker for progression of the tumors and the poor prognosis of the patients in endometrioid adenocarcinomas.

Mitochondrial transcription factor A regulates BCL2L1 gene expression and is a prognostic factor in serous ovarian cancer.

Mitochondrial transcription factor A (mtTFA) is necessary for both transcription and maintenance of mitochondrial DNA (mtDNA). Recently, we reported that mtTFA is expressed not only in mitochondria, but also in nuclei. However, the function of mtTFA in the nucleus has not been clearly elucidated. In the present study, we examined nuclear mtTFA expression in 60 tissue samples of serous ovarian cancer using immunohistochemical analysis and found that 56.7% of serous ovarian cancer patients were positive for mtTFA, whereas 43.3% were negative. Univariate survival analysis showed that the overall 5‐year survival rate was significantly worse for patients with mtTFA‐positive cancer compared with mtTFA‐negative cancer (32%vs 42%, respectively; P = 0.021). To elucidate the function of mtTFA in the nucleus, we investigated BCL2L1, a target gene of mtTFA. There was a significant correlation between nuclear mtTFA expression and BCL2L1 expression in seven ovarian cancer cell lines and in specimens of clinical ovarian cancer. Cellular BCL2L1 was downregulated following transfection of siRNA against mtTFA. BCL2L1 promoter activity was increased after transfection of mtTFA expression plasmid, but decreased after siRNA knockdown of mtTFA. Chromatin immunoprecipitation assays showed that mtTFA was bound to the BCL2L1 promoter region. These results suggest that mtTFA is a prognostic factor for a poor outcome of ovarian cancer and may function as an antiapoptotic factor, regulating genes such as BCL2L1. Furthermore, mtTFA may be a promising molecular target for novel therapeutic strategies for the treatment of ovarian cancer. (Cancer Sci 2012; 103: 239–244)

Cytologic Analysis of Primary Stomach Adenocarcinoma Metastatic to the Uterine Cervix

OBJECTIVE To investigate the cytologic and pathologic features of endocervical lesions in cases of gastric adenocarcinoma metastatic to the uterine cervix. STUDY DESIGN From 1986 to 1994, four patients with gastric adenocarcinoma metastatic to the uterine cervix were treated at our department. The cervical cytologic samples were obtained by swabbing and were stained by the Papanicolaou method. Presence of tumor diathesis, number of atypical cells, cell arrangement, cytoplastic vacuoles, cellular and nuclear diameter, chromatin distribution and size of the nucleolus were investigated. RESULTS The smear backgrounds were dirty (tumor diathesis) in two cases and clean in two. No significant difference in the number of atypical cells or in cell or nuclear diameter between primary and metastatic adenocarcinoma was shown. Cell arrangement was the different cytologic finding between primary and metastatic adenocarcinoma. Sheetlike or isolated arrangement was seen frequently in metastatic cervical adenocarcinoma. CONCLUSION Because different cytologic features have been found in past and the present series, cytologic diagnosis of metastatic cervical adenocarcinoma should be made carefully.

Epithelial ovarian cancer: definitive radiotherapy for limited recurrence after complete remission had been achieved with aggressive front-line therapy

The purpose of this study was to assess the efficacy and toxicity of definitive radiotherapy (RT) for the recurrence of epithelial ovarian cancer, which is limited to one or two gross regions, after complete remission had been achieved with aggressive front-line therapy. Twenty-seven patients were treated with definitive RT and were retrospectively analyzed. Their median tumor size was 3.0 cm. Twenty-six (96%) patients received external irradiation at a median total dose of 60 Gy, and a median daily dose of 2 Gy. Only two patients received intracavitary brachytherapy. Twenty (74%) of the 27 patients received systemic chemotherapy for the treatment of a limited recurrent tumor followed by definitive RT. Six (22%) of the patients received concurrent chemotherapy and seven (26%) of the patients also underwent regional hyperthermia during definitive RT. Twenty-two (82%) patients had an objective response (CR: 11, PR: 11). The 2-year overall survival, progression-free survival and local (in-field) control rates after RT were 53%, 39% and 96%, respectively. The toxicities were mild, no Grade 3 or higher toxicity was observed in any of the patients. The tumor size( < 3 cm), period between front-line therapy and RT (≥2 year) and objective tumor response (CR) were significant prognostic factors of the overall survival rate. In conclusion, definitive RT for limited recurrence of epithelial ovarian cancer achieves a better local control rate without severe toxicity, and it may therefore be a potentially effective modality for inducing long-term survival in selected patients.

Low Grade Cervical Intraepithelial Neoplasia Associated with Human Papillomavirus Infection

OBJECTIVE To investigate the correlation between the development of low grade cervical intraepithelial neoplasia (LCIN) and human papillomavirus (HPV) infection in cases with long-term follow-up. STUDY DESIGN Forty-three cases of LCIN were followed for more than five years with cytology, colposcopy and Vira Pap. Coexistence of HPV infection was sought using a simplified HPV detection kit, the Vira Pap method (Dot Blot hybridization). RESULTS Regressive disease was noted in 21 cases, and persistent and progressive disease was noted in 22 cases. HPV DNA was negative in 81% (17 of 21) of regressive disease and positive in 55% (12 of 22) persistent and progressive disease. LCIN had disappeared in 17 (63%) of 27 cases negative for HPV DNA and was persistent or progressive in 12 (75%) of 16 cases positive for HPV DNA. CONCLUSION The clinical course of LCIN correlates well with HPV infection.

Myxoid Leiomyosarcoma of the Uterus

BACKGROUND: Myxoid leiomyosarcoma is a rare variant of uterine sarcoma, exhibiting malignant biologic behavior despite the absence of cytologic atypia and of significant mitotic activity. CASE: A 20-year-old female was referred with a cystic pelvic mass. At laparotomy, the tumor, weighed 2,200 g and originating in the left lateral uterine wall, was removed. Microscopic examination revealed well-differentiated smooth muscle cells without atypia and with a few mitotic figures in the copious myxoid matrix, suggesting myxoid leiomyosarcoma. Three years following laparotomy, an irregular mass around the uterus was noted on sonographic examination, suggesting local recurrence. Two years and six months later, the second operation was performed, and a locally recurrent, multicystic tumor weighing 3,500 g was excised. The histopathology was similar to that of the primary tumor. Cytologic findings on imprint material from the tumor revealed a few isolated or sheet like small cells consisting of spindle and polygonal cells with round and oval nuclei. Cytologic atypia was also minimal. CONCLUSION: Myxoid leiomyosarcoma should be included in the differential diagnosis of smooth muscle neoplasia.

Expression of estrogen receptor-α as a prognostic factor in patients with uterine serous carcinoma.

Objectives Although the expression of estrogen receptor (ER) is usually found in uterine endometrioid adenocarcinomas, it has recently been reported to be found in some uterine serous carcinomas (USCs). This report describes the clinicopathologic features of USC with an expression of ER-&agr;, with special reference to the prognostic significance of ER-&agr;. Methods The immunohistochemical expression of ER-&agr; was examined in 33 USCs. Greater than 10% staining was defined as an overexpression of ER-&agr;. Cox univariate and multivariate analyses for USCs were performed. Results A total of 7 USCs (21.2%) exhibited an expression of ER-&agr;. All tumors were pure-type USCs and strongly demonstrated an overexpression of p53. The cancer-specific 5-year survival rates of patients with USC without an expression of ER-&agr; and USC with an expression of ER-&agr; were 54.5% and 0.0%, respectively (P = 0.04). The univariate analyses showed an expression of ER-&agr; to be a significant prognostic indicator in patients with USC (P < 0.05). However, multivariate analyses for USCs showed that the surgical stage was an independent prognostic factor, whereas the significance of ER immunoreactivity disappeared. Conclusions Uterine serous carcinoma with an expression of ER-&agr; was associated with advanced-staged tumors and a significantly worse prognosis than that without an expression of ER-&agr;. When an endometrial biopsy specimen reveals USC with an expression of ER-&agr; and an overexpression of p53, the presence of an extrauterine lesion is suggested.

Trends in the demographic and clinicopathological characteristics in Japanese patients with endometrial cancer, 1990-2010.

Objective Over the past 20 years, the incidence of endometrial cancer has increased remarkably in Japan. The number of elderly females has also increased within the population of Japan. We examined the impact of advanced age on the demographic and clinicopathological characteristics in Japanese patients with endometrial cancer. Methods Data were collected from 319 surgically treated Japanese females with endometrial cancer from the files of the University Hospital of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan, between 1990 and 2010. χ2 tests were performed to evaluate the trends in the variables between two decades (A: 116 cases from 1990–2000) and (B: 203 cases in 2001–2010). The histological subtypes were also evaluated based on the immunohistochemical expressions of p53, estrogen receptor, and Ki-67. Results The mean ages ± standard deviation in the decade A group and the decade B group were 57.5 years ± 9.7 years and 61.0 years ± 11.3 years, respectively (P < 0.02). There was an increase in the proportion of patients aged 70 years or older and of high-risk histological tumors including serous carcinoma, clear cell carcinoma, and carcinosarcoma (decade A group and decade B group: 9.5% vs 27.6%, P < 0.001, 10.4% vs 21.6%, P = 0.01, respectively), while the advanced surgical stage (III and IV), obesity (≥25 of body mass index), and nulliparity of the decade A group and decade B group were 23.3% vs 29.1%, P = 0.30, 28.4% vs 33.0%, P = 0.40, and 19.0% vs 21.2%, P = 0.66, respectively. The cancer-specific survival rates in the decade A group and the decade B group were 78.6% and 77.6%, respectively (P = 0.93). Conclusion The increase in number of elderly females in the Japanese population is related to the increase in that of high-risk endometrial cancers. A study is needed to investigate prevention strategies and to improve the treatment of elderly patients with high-risk endometrial cancer.

Prognostic significance of overexpression of p53 in uterine endometrioid adenocarcinomas with an analysis of nuclear grade

Although overexpression of p53 is usually found in uterine serous carcinoma (USC), it is also found in some uterine endometrioid adenocarcinomas (UEA). This report describes the clinicopathological features of the UEA with overexpression of p53 with special reference to a prognostic significance of nuclear grade.