Yasunari Miyagi

Rapid and sensitive detection of physical status of human papillomavirus type 16 DNA by quantitative real-time PCR

ABSTRACT A rapid quantitative real-time PCR method was employed to quantify the copy number of E2 and E6 genes for analysis of the physical status of human papillomavirus type 16 (HPV-16) DNA. Significant differences with respect to both copy numbers were found when more than 40% of HPV-16 DNA was integrated with disruption of the E2 gene in an experimental model. The physical status of HPV-16 DNA in 50 clinical samples was exclusively episomal in 21 cases (42%), concomitant in 14 cases (28%), and integrated in 15 cases (30%). The prevalence of integrated and/or concomitant forms of HPV-16 DNA increased with progression of cervical disease. Four of 11 cervical intraepithelial neoplasia involved integrated forms of HPV-16 DNA partially or exclusively. This rapid, sensitive technique is useful in the analysis of the physical status of HPV DNA.

Serum C-reactive protein as a prognostic factor in patients with epithelial ovarian cancer

OBJECTIVE It is well known that the serum level of Interleukin-6 (IL-6) correlates with the level of C-reactive protein (CRP). The purpose of this study is to determine the significance of CRP as a prognostic factor in epithelial ovarian cancer. STUDY DESIGN The present study is comprised of 120 patients with epithelial ovarian cancer from 1985 to 1992. In this study, CRP levels above 50 mg/l were considered high CRP. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with poor survival. RESULTS The serum CRP value was significantly associated with the volume of ascites (P = 0.000004). Univariate analysis showed that the FIGO stage, primary tumour diameter, size of residual tumour, histologic grade, volume of ascites and high serum level of CRP were significant prognostic factors. Coxs multivariate proportional hazard model showed that histologic grade was the most important prognostic factor (P = 0.0026). FIGO stage and volume of ascites were also independent factors for 5-year survival (P = 0.0310 and P = 0.0216, respectively). However, the serum CRP value was not an independent prognostic factor. CONCLUSION CRP is an adverse prognostic factor in univariate analysis, but not in multivariate analysis.

Vascular endothelial growth factor is implicated in early invasion in cervical cancer.

The association between the expression of vascular endothelial growth factor (VEGF) and clinicopathological factors has scarcely been examined in cervical cancer. This study examines the level of VEGF messenger RNA (mRNA) expression in invasive cervical cancer and its association with clinicopathological features including microvessel density. The level of VEGF mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) using beta-actin as an internal control in 66 patients with stages Ia-IVb invasive cervical cancer. In 42 patients who underwent surgery, the microvessel count was also assessed by immunostaining for factor VIII-related antigen in the most neovascularised area of the specimen. The highest level of VEGF mRNA expression was observed in early invasive cervical cancers. Except for stage IVb, the stage of the disease inversely correlated with the level of VEGF mRNA (P < 0.05). There was no significant difference in the level of VEGF mRNA with respect to histological cell types. 38 patients with stages Ib-IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. There was no significant difference in the level of VEGF mRNA with respect to lymph node metastasis, depth of stromal invasion, tumour size, parametrial involvement or vaginal involvement among these patients. A significant relationship was found between the microvessel density and the level of VEGF mRNA (P < 0.01). These findings provide evidence that the expression of VEGF is involved in the promotion of angiogenesis in cervical cancer and plays an important role in early invasion.

Sclerosing stromal tumor of the ovary: US, MR, and dynamic MR findings

The US, MR, and dynamic MR findings in four patients with sclerosing stromal tumor of the ovary are reported. US showed a tumor with multilocular cystic components and irregularly thickened septa and tumor walls or a solid tumor including several small cystic components. On T2-weighted MR images, signal intensities of the cystic components were high and those of the solid components were inhomogeneous, ranging from intermediate-high to high. Dynamic MRI demonstrated marked early enhancement of the solid components.

Endometrial carcinoma: efficacy of thin-section oblique axial MR images for evaluating cervical invasion

AbstractBackground: To investigate the efficacy of thin-section oblique axial magnetic resonance (MR) images in evaluating cervical invasion by endometrial carcinoma. Methods: Sixty-seven patients with endometrial carcinoma were evaluated with pathologic correlation. We compared the accuracy in the assessment of cervical invasion by endometrial carcinoma between parasagittal MR images and thin-section oblique axial MR images by using T2-weighted and contrast-enhanced T1-weighted pulse sequences. Results: Cervical invasion by endometrial carcinoma was confirmed by pathologic examination. Cervical invasion was seen in 16 patients. The accuracy rates of parasagittal T2-weighted images, thin-section oblique axial T2-weighted images, parasagittal contrast-enhanced T1-weighted images, and thin-section oblique axial contrast-enhanced T1-weighted images were 74.7%, 89.5%, 82.0%, and 95.5%, respectively. Statistically significant differences were seen between parasagittal T2-weighted images and thin-section oblique axial T2-weighted images (p= 0.002) and between parasagittal contrast-enhanced T1-weighted images and thin-section oblique axial contrast-enhanced T1-weighted images (p= 0.003). Conclusion: Thin-section oblique axial MR images are considered to be useful for the assessment of cervical invasion by endometrial carcinoma.

Phase II study of intraperitoneal carboplatin with intravenous paclitaxel in patients with suboptimal residual epithelial ovarian or primary peritoneal cancer: a Sankai Gynecology Cancer Study Group Study.

Purpose: To assess the antitumor efficacy and safety of 2 treatment modalities: intraperitoneal carboplatin combined with intravenous (IV) paclitaxel. Patients and Methods: Eligible patients were those with epithelial ovarian carcinoma or primary peritoneal carcinoma stages II to IV who underwent initial surgery and had a residual tumor size of 2 cm or larger. Patients received IV paclitaxel 175 mg/m2 followed by intraperitoneal carboplatin AUC6. The primary end point was a response. Secondary end points were toxicity, progression-free survival, and overall survival. Results: Twenty-six patients were enrolled, and 24 patients were eligible for assessment. The response rate was 83.3% (95% CI, 62.6%-95.3%; Table 4). The median progression-free survival was 25 months. The median overall survival had not been reached. Incidences of grade (G) 3/4 hematological toxicities were absolute neutrophil count, 96%; hemoglobin, 29%; and thrombocytopenia, 16%. Nonhematological toxicities included G2 liver function, 4%; G3 sensory neuropathy, 8%; and G3 myalgia and arthralgia, 4%. Conclusions: Intraperitoneal administration of carboplatin combined with IV paclitaxel was well tolerated and showed satisfactory response in the patients with bulky residual tumor. Large-scale phase III trial comparing with IV carboplatin is warranted in this patient population.

CD44 exon v6 is not implicated in the progression and metastasis of endometrial cancer

We examined the presence of mRNA for CD44v6 and assessed the association with clinicopathological features in 42 patients with endometrial cancer by RT-PCR and subsequent Southern blot hybridization with oligonucleotide probe specific for v6. The standard form of CD44 was expressed in all specimens and 20 out of 42 endometrial cancers expressed an isoform containing exon v6 in combination with other variant exons. However, there was no correlation between the expression of CD44v6 and any clinicopathological factors. These findings suggested that the expression of CD44v6 is not implicated in the progression and metastasis of endometrial cancer.

Cervical carcinoma with full-thickness stromal invasion: Relationship between tumor size on T2-weighted images and parametrial involvement

Purpose The purpose of this work was to investigate the relationship between tumor size on T2-weighted images and parametrial involvement by cervical carcinoma with full-thickness stromal invasion and to evaluate whether the size of the tumor on T2-weighted images is a useful index of parametrial involvement. Method T2-weighted images of 33 patients with cervical carcinoma showed full-thickness stromal invasion. Three-dimensional diameters (transverse, anteroposterior, and craniocaudal) of the primary tumor were measured on T2-weighted images. The area and volume of the tumor were also calculated. Results There were statistically significant differences between the patients with parametrial involvement and those without parametrial involvement for each tumor size. The criteria that showed the best accuracy for each tumor size were determined. Conclusion The tumor size on T2-weighted images is considered to be a useful index for evaluating parametrial involvement by cervical carcinoma with full-thickness stromal invasion.

CD44 exon v6 correlates with cellular differentiation but not with progression and metastasis of cervical cancer

The purpose of this study was to investigate whether CD44v6 expression correlates with progression or metastasis of cervical cancer. The presence of mRNA for CD44v6 was examined, the association with clinicopathological features was assessed in 80 patients with cervical cancer by reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent Southern blot hybridisation with an oligonucleotide probe specific for v6. The standard form of CD44 was expressed in all specimens and 53 of 80 cervical cancers expressed an isoform containing exon v6 in combination with other variant exons. In addition, longer size transcripts of more than 1350 bp (long form) were identified in 22 of the 53 CD44v6 positive patients. The expression of CD44v6 and CD44v6 long form in squamous cell carcinomas was significantly higher than that in non-squamous cell carcinomas (P < 0.001). The expression of CD44v6 long form in histological grade 1 and 2 was significantly higher than that in grade 3 (P < 0.05). 47 patients in stage Ib-IIb cervical cancers were treated by radical hysterectomy and pelvic lymphadenectomy. We did not find any association between the expression of the long form or the short form of CD44v6 and any pathological features, except for histological cell type. These findings suggest that the regulation of CD44v6 seems to be different between different histological cell types and different tumour grades, and the expression of CD44v6 might not be implicated in the progression and metastasis of cervical cancer.

The Expression of Platelet-Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase Associates with Angiogenesis in Epithelial Ovarian Cancer

BackgroundThe object of this study is to clarify the association of an angiogenic factor, PD-ECGF (platelet-derived endothelial cell growth factor/thymidine phosphorylase), with clinicopathologic factors, in this case tumor angiogenesis, in epithelial ovarian cancers.MethodsTumor specimens were obtained at the time of surgery from the primary lesion in 60 patients with epithelial ovarian cancer. Histologic cell types were assigned to tumors according to the World Health Organization classification: 26 were classified as serous adenocarcinoma, 15 as endometrioid adenocarcinoma, 9 as mucinous adenocarcinoma, 9 as clear cell carcinoma, and 1 as undifferentiated carcinoma. Surgical staging was based on the international Federation of Gynecology and Obstetrics (FIGO) staging system: 16 were stage I, 6 were stage II, 34 were stage III, and 4 were stage IV. Expression of PD-ECGF was evaluated by immunohistochemical staining. Microvessel density was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area.ResultsStroma cells stained more strongly than cancer cells (80% vs. 33%). The immunopositivity of PD-ECGF in stroma cells was higher in cases of advanced cancer. Expression of PD-ECGF in mucinous adenocarcinomas was significantly higher than that in serous adenocarcinomas, while PD-ECGF expression in clear cell carcinomas was significantly lower. The microvessel density in the cases with marked PD-ECGF-positive stroma cells was significantly higher than that in the cases with absent/minimal PD-ECGF-positive stroma cells (P<0.05).ConclusionThe expression of PD-ECGF may play a crucial role in the promotion of angiogenesis in epithelial ovarian cancers.