Noriko Seki

Vascular endothelial growth factor-C expression and its relationship to pelvic lymph node status in invasive cervical cancer.

Vascular endothelial growth factor-C (VEGF-C) has been implicated in lymphangiogenesis, the process of new lymphatics formation. The present study investigated VEGF-C mRNA expression in invasive cervical cancer tissue. Additionally, the association of VEGF-C mRNA with clinicopathological features was examined. VEGF-C mRNA expression was assessed by reverse transcription-polymerase chain reaction using β-action as an internal control. 75 patients presenting with invasive cervical cancer were included in the trial. VEGF-C mRNA expression was markedly higher in tumours in which pelvic lymph node metastasis was diagnosed by magnetic resonance (MR) imaging (P = 0.002). 53 patients displaying stage Ib–IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. VEGF-C expression was significantly higher in tumours exhibiting deep stromal invasion, pelvic lymph node metastasis and lymph-vascular space involvement (P = 0.016, P = 0.006 and P = 0.036, respectively). Multivariate analysis revealed VEGF-C mRNA expression to be the sole independent factor influencing pelvic lymph node metastasis. Subjects demonstrating VEGF-C mRNA expression displayed significantly poorer prognoses than those lacking VEGF-C mRNA expression (P = 0.049). These findings provide evidence supporting the involvement of VEGF-C expression in the promotion of lymph node metastasis in cervical cancer. Furthermore, examination of VEGF-C expression in biopsy specimens may be beneficial in the prediction of pelvic lymph node metastasis.

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.

Factors associated with parametrial involvement in stage IB1 cervical cancer and identification of patients suitable for less radical surgery

OBJECTIVE The purpose of the present study was to determine possible factors associated with parametrial spread in patients with stage IB1 cervical cancer and define parameters associated with a low risk for parametrial spread, in order to identify candidates for less radical surgery. PATIENTS AND METHODS We retrospectively reviewed 200 patients with stage IB1 cervical cancer who had undergone radical hysterectomy (class III) and pelvic lymphadenectomy. RESULTS Overall, 20 (10.0%) of the 200 patients revealed parametrial spread, of which 11 (55%) had only direct microscopic extension of the disease, 3 (15%) had only disease spread to parametrial lymph nodes, 1 (5%) had both direct microscopic extension and disease spread to parametrial lymph nodes, and 5 (25%) had only tumor emboli within the lymph vascular channels in the parametrial tissue. Elderly age, depth of invasion, tumor size, lymph vascular space invasion (LVSI), positive pelvic nodes, and ovarian metastasis were significantly associated with parametrial involvement. The multivariate analysis model included factors that could be determined by a cone biopsy and showed LVSI, deep stromal invasion, and elderly age to be the independent predictors of parametrial involvement. Ninety-one patients had a depth of invasion of ≤10 mm and no LVSI, of which only 1 (1.1%) had parametrial involvement. When patients aged ≤50 years were further stratified into those with a depth of invasion of ≤10 mm and no LVSI, parametrial involvement was found to be 0.0% (0/68). CONCLUSION Patients with a tumor depth of invasion of ≤10 mm, no LVSI, and aged ≤50 years, could be considered for less radical surgery such as modified radical hysterectomy or simple hysterectomy with pelvic lymphadenectomy.

The mean apparent diffusion coefficient value (ADCmean) on primary cervical cancer is a predictive marker for disease recurrence

OBJECTIVE The purpose of this study is to investigate the correlation of the max, mean and minimal apparent diffusion coefficient values (ADCmax, ADCmean, and ADCmin) on diffusion weighted imaging findings with prognostic factors in cervical cancer. METHODS A cohort of 80 cervical cancer patients underwent pelvic magnetic resonance imaging (MRI) within the 2 to 4 weeks prior to radical hysterectomy. The optimal cutoff value for segregating disease free survival (DFS) was determined by receiver operating characteristic (ROC) curve analysis. We used ROC curve analyses to evaluate whether preoperative ADCmax, ADCmean, ADCmin on MRI predicted the risk group of recurrence. RESULTS Analyses of ROC curves identified an optimal The ROC curves identified an optimal ADCmax, ADCmean, and ADCmin cutoff values of 1.122 × 10(-3)mm(2)/s, 0.852 × 10(-3)mm(2)/s, 0.670 × 10(-3)mm(2)/s and for predicting the recurrence of cervical cancer. The patients categorized into the lower ADCmean or ADCmin groups showed the shorter disease free survivals compared with the higher ADCmean or ADCmin, respectively (P<0.0001 or P=0.0210). In particular, the ADCmean of primary cervical cancer was an independent predictive factor for disease recurrence by a multivariate analysis (P=0.0133). CONCLUSIONS The ADCmean of primary cervical cancer calculated by MRI could be an important factor for identifying patients with a risk of disease recurrence.

Vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression are implicated in the angiogenesis of endometrial cancer.

Although many angiogenic factors have been described, it is not well defined which factors are expressed in endometrial cancer. The object of this study was to examine mRNA levels of the two angiogenic factors, vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in endometrial cancer tissues and their association with clinicopathological features including microvessel density. The level of VEGF and PD-ECGF mRNAs was assessed by semi-quantitative reverse transcription-polymerase chain reaction using beta-actin as an internal standard in 38 patients with endometrial cancer. Microvessel counts were also assessed by immunostaining for factor VIII-related antigen in the most vascularised area of the specimen. VEGF/beta-actin ratios of non-endometrioid tumours were significantly higher than those of endometrioid tumours (P = 0.013). VEGF/beta-actin ratios of cases with lymph-vascular space involvement were significantly higher than those of cases without lymph-vascular space involvement (P = 0.021). Although it was not statistically significant, PD-ECGF/beta-actin ratios in grade 3 tumours were higher than those in grade 1 and 2 tumours (P = 0.066). The microvessel density was significantly correlated with the level of VEGF and PD-ECGF mRNA expression (P = 0.041 and P < 0.0001, respectively). Our findings provide evidence that the expression of both VEGF and PD-ECGF is involved in the promotion of angiogenesis in endometrial cancer. In addition, VEGF and PD-ECGF might contribute to the aggressive potential of high grade tumours or certain histological subtypes with unfavourable prognosis through the induction of angiogenesis.

Prognostic factors in stage IB-IIB cervical adenocarcinoma patients treated with radical hysterectomy and pelvic lymphadenectomy

The purpose of the present study was to identify prognostic factors and patterns of recurrence in patients with stage IB–IIB cervical adenocarcinoma who had undergone radical surgery and to compare these patterns with those observed in squamous cell carcinoma (SCC) patients.

The preoperative SUVmax is superior to ADCmin of the primary tumour as a predictor of disease recurrence and survival in patients with endometrial cancer

PurposeThe purpose of this study was to investigate the prognostic value of the minimum apparent diffusion coefficient (ADCmin) derived from diffusion-weighted MR imaging and of the maximum standardized uptake value (SUVmax) derived from PET/CT imaging of the primary tumour in patients with endometrial cancer.MethodsSUVmax reflects the highest tumour metabolism rate and ADCmin reflects the highest cellularity, and both parameters have been used for tumour grading and prediction of prognosis. The correlations between prognosis and SUVmax and ADCmin of the primary tumour were determined in 131 patients with endometrial cancer. The patients were divided into groups based on ADCmin and SUVmax cut-off values to predict recurrence and survival, which were derived from receiver operating characteristic curves. Disease-free survival (DFS) and overall survival (OS) of the groups were analysed using the Kaplan-Meier method, and differences between survival curves were evaluated using the log-rank test.ResultsThe median DFS and OS times of all patients were 19.2 and 20.5 months (follow-up periods 1–70 months for both DFS and OS), respectively. Patients with high SUVmax had significantly lower DFS (P < 0.0001) and OS (P = 0.0092) than patients with low SUVmax. Multivariate analysis showed that high SUVmax was an independent prognostic factor for both DFS (P = 0.0161) and OS (P = 0.0232).ConclusionThe SUVmax of the primary tumour derived from PET/CT imaging could be an important prognostic indicator of recurrence and survival in patients with endometrial cancer.

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.

D-dimer level as a risk factor for postoperative venous thromboembolism in Japanese women with gynecologic cancer

BACKGROUND The purpose of the present study was to evaluate whether early postoperative D-dimer levels and certain pre-, intra-, and postoperative parameters can be used to predict venous thromboembolism (VTE) in gynecologic cancer patients. MATERIALS AND METHODS We prospectively evaluated 267 gynecologic cancer patients who underwent surgery at our institution. The plasma D-dimer level was measured serially before the operation and on certain postoperative days. After the operation, primary screening for VTE was undertaken by meticulous examination for clinical signs and elevation of the plasma D-dimer level. Seventy-five patients underwent multidetector row computed tomography and were subjected to further investigations. RESULTS VTE was detected in 21 of the 75 patients. There were significant differences in the D-dimer value between VTE-positive and VTE-negative patients on postoperative days 3, 5, and 7. The optimal cut-off value for the postoperative D-dimer level was determined as 5 mug/ml on day 3. Logistic regression multivariate analysis revealed that high D-dimer values on postoperative day 3, the use of recombinant human erythropoietin (rHuEPO), and non-O blood group were independent risk factors for postoperative VTE. CONCLUSION High plasma D-dimer level on postoperative day 3, the use of rHuEPO, and non-O blood group were independent risk factors for postoperative VTE.