Jun Chikumi

Accuracy of semiquantitative dynamic contrast-enhanced MRI for differentiating type II from type I endometrial carcinoma.

To investigate type II endometrial carcinoma characterization using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and evaluate the diagnostic accuracy of semiquantitative DCE‐MRI in differentiating type II from type I tumors.

Serum Vascular Endothelial Growth Factor-a as a Prognostic Biomarker for Epithelial Ovarian Cancer

Background Bevacizumab, which targets vascular endothelial growth factor (VEGF)-A, has recently been proven to be effective for the treatment of epithelial ovarian cancer (EOC). Thus, interest in VEGF-A has increased. There are few reports on concomitant detection of both ligands and its soluble receptors in serum samples, and the significance of serum VEGF-A in EOC is unclear, unlike the situation with tissue samples. We conducted the present study to explore the levels of serum VEGF family and its receptors and to evaluate their utility as prognostic biomarkers. Methods A total of 128 patients with EOC, who were consecutively treated at Tottori University Hospital between 2006 and 2012, were included. Blood samples were collected before initial surgery. Serum concentrations of VEGF-A, VEGF-C, VEGFR-1, and VEGFR-2 were analyzed by enzyme-linked immunosorbent assay. We also examined the mRNA and protein expression of VEGF-A in tumor tissue from 30 cases by real-time reverse transcription polymerase chain reaction and immunohistochemistry. Results The levels of VEGF-A in patients with stage III/IV disease were significantly higher than those with stage I/II disease (P = 0.0036). On the other hand, the level of VEGFR-2 in stage III/IV was significantly lower than that in stage I/II (P = 0.0026). With the cutoff value of VEGF/VEGFRs at the median level, the overall survival (OS) for patients with high VEGF-A levels was significantly lower than those with low levels (P = 0.015). Patients with high VEGFR-2 levels showed better prognosis than those with low VEGFR-2 levels (P = 0.023). Multivariate analysis revealed that International Federation of Gynecology and Obstetrics stage and serum VEGF-A were independent prognostic factors for OS [hazard ratio 2.01, 95% confidence interval (1.13–3.63), P = 0.017]. There was no significant correlation between mRNA or protein expression and serum levels of VEGF-A. Conclusions Serum VEGF-A is an independent prognostic factor for OS in patients with EOC, implying that serum VEGF-A is a prognostic biomarker for EOC. Further study to validate the data is needed.

Recurrent colon perforation after discontinuation of bevacizumab for ovarian cancer

Bevacizumab (Bev) is an antiangiogenic drug used to treat various malignances, including ovarian cancer (OC). Bev is generally well-tolerated; however, it has a characteristic toxicity profile. In particular, gastrointestinal perforation (GIP) is a rare but serious side effect that can be lethal. A 55-year-old woman with recurrent OC had an episode of GIP during third-line chemotherapy comprising Bev and topotecan (TPT). Bev was discontinued while TPT was continued as monotherapy. Three months after discontinuation of Bev, the patient presented with left lower abdominal pain and was diagnosed with a second GIP. She had emergent surgery. One year later, she is still alive and healthy, and is continuing TPT. This is the first report of recurrent GIP after discontinuation of Bev. Our case suggests that physicians should be aware of GIP even after the discontinuation of Bev.

Significance of High-Risk Human Papillomavirus Testing for Atypical Glandular Cells on Cervical Cytology

Objectives: The aim of this study was to evaluate the diagnostic significance of high-risk human papillomavirus (hrHPV) testing for managing women with atypical glandular cells (AGC) and to explore the distribution of hrHPV genotypes. Methods: We analyzed cytologic and histopathologic diagnoses in patients referred to our institution due to AGC or atypical squamous cells of undetermined significance (ASC-US). All patients underwent hrHPV testing and genotyping, and positive (PPV) and negative predictive values (NPV) for cervical intraepithelial neoplasia (CIN) 2 or worse [CIN2+/adenocarcinoma in situ (AIS)+] were calculated. Results: Among 41 cases previously diagnosed with AGC, 22 (53%) were classified as CIN2+ (2 squamous cell carcinomas), whereas only 2 were AIS or adenocarcinoma. Twenty-seven (65.8%) cases in the AGC group were hrHPV positive. The most frequent genotypes in both the ASC-US and AGC groups were HPV16 and HPV52. The PPV of hrHPV testing for CIN2+/AIS+ was significantly higher in the AGC than in the ASC-US group (74.1 vs. 35.0%; p = 0.0005). The NPV for CIN2+/AIS+ was significantly lower in the AGC than in the ASC-US group (74.4 vs. 100%; p = 0.0441). Conclusion: In patients with AGC, both glandular and squamous lesions must be monitored. hrHPV testing is useful for detecting CIN2+/AIS+ in AGC.

Abstract 3386: Serum VEGF-A may predict prognosis in patients with uterine cervical cancer

Objective: Angiogenesis is one of the processes that is critical for the growth, invasion and metastasis of solid tumors, including uterine cervical cancer (CC). The vascular endothelial growth factor (VEGF) family is one of the major pathways involved in tumor angiogenesis. The aim of this study was to determine whether serum levels of these angiogenic factors could be used as biomarkers in patients with CC. Methods: A total of 115 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IIB CC who were treated at Tottori University Hospital between 2006 and 2015 were enrolled in this study. The study was approved by the Institutional Review Board of the School of Medicine of Tottori University. All patients gave written informed consent before the collection of specimens according to institutional guidelines. Serum samples were collected before initial surgery and levels of VEGF-A, -C and VEGFR1 were analyzed by enzyme-linked immunosorbent assay (ELISA). We evaluated the association between the levels of VEGF-A, -C, and VEGFR1 and clinicopathologic variables. Survival analysis was performed with 86 patients treated between 2006 and 2013. We also determined the mRNA expression VEGF-A, -C, and VEGFR1 by real-time RT-PCR in fresh frozen tumors and the protein expression by immunohistochemical staining in paraffin-embedded tumors from CC patients. Results: The mRNA and protein expressions of VEGF-A, -C, and VEGFR1 were strongly observed in the cancer cells. Median levels of serum VEGF-A, -C and VEGFR1 were 313, 8404 and 67.2 pg/ml, respectively. The levels of VEGF-A in patients with lymph node involvement were significantly higher than those in patients without it. On the contrary, the levels of VEGFR1 in patients with lymph node involvement were significantly lower than those in patients without it. Both histological types and FIGO stage were not related to levels of these angiogenic factors. We found a significant positive correlation between VEGF-A levels and the maximum tumor diameter. There was a significant negative correlation between VEGFR1 levels and the maximum tumor diameter. The overall survival rate was significantly lower in FIGO stage IIB than stage IB- IIA patients. We set the cutoff value of these factors at the median levels of each angiogenic factors. The 5-year survival rate for patients with high VEGF-A levels was significantly lower than those with low levels (92.9% vs. 72.8%, P = 0.014). Both VEGFR1 and VEGF-C levels were not related to outcome of patients. Multivariate analysis revealed that serum VEGF-A level and FIGO stage were independent prognostic factors. Conclusion: These results suggest that serum VEGF-A may be a promising prognostic biomarker for CC. Citation Format: Mayumi Sawada, Tetsuro Oishi, Hiroaki Komatsu, Hiroaki Itamochi, Michiko Nonaka, Seitya Sato, Jun Chikumi, Sinya Sato, Sinya Sato, Muneaki Shimada, Tasuku Harada. Serum VEGF-A may predict prognosis in patients with uterine cervical cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3386.

Abstract 3387: Serum VEGF-A may predict prognosis in patients with epithelial ovarian cancer

Objective: Angiogenesis is one of the processes that is critical for the growth, invasion and metastasis of solid tumors, including epithelial ovarian cancer (EOC). The vascular endothelial growth factor (VEGF) family is one of the major pathways involved in tumor angiogenesis. The aim of this study was to determine whether serum levels of these angiogenic factors could be used as biomarkers in patients with EOC. Methods: A total of 133 patients with EOC who were treated at Tottori University Hospital between 2006 and 2014 were enrolled in this study. The study was approved by the Institutional Review Board of the School of Medicine of Tottori University. All patients gave written informed consent before the collection of specimens according to institutional guidelines. Serum samples were collected before initial surgery and levels of VEGF-A, -C and VEGFR1 were analyzed by enzyme-linked immunosorbent assay (ELISA). We evaluated the association between the levels of VEGF-A, -C, and VEGFR1 and clinicopathologic variables. We also determined the mRNA expression VEGF-A, -C, and VEGFR1 by real-time RT-PCR in fresh frozen tumors and the protein expression by immunohistochemical staining in paraffin-embedded tumors from EOC patients. Additionally, serum samples were collected before and after bevacizumab treatment, and levels of angiogenic factors were examined. Results: The mRNA and protein expressions of VEGF-A, -C, and VEGFR1 were strongly observed in the cancer cells. Median levels of serum VEGF-A, -C and VEGFR1 were 284, 4861 and 417 pg/ml, respectively. The levels of VEGF-A ans VEGFR1 in patients at stage III-IV were significantly higher than those in patients at stage I-II. Both histologic subtypes and lymph node involvement were not related to levels of these angiogenic factors. We found a significant positive correlation between VEGF-A levels and the ascitic volume. The overall survival rate was significantly lower in FIGO stage III or IV patients with EOC. We set the cutoff value of these factors at the median levels of each angiogenic factors. The 5-year survival rate for patients with high VEGF-A levels was significantly lower than those with low levels (60.7% vs. 45.5%, P = 0.029). Both VEGFR1 and VEGF-C levels were not related to outcome of patients. Multivariate analysis revealed that serum VEGF-A level and FIGO stage were independent prognostic factors. VEGF-A levels dramatically decreased after treatment with bevacizumab. Conclusion: These results suggest that serum VEGF-A may be a promising prognostic biomarker for EOC. Further study is needed to determine if could be predictive biomarker. Citation Format: Hiroaki Komatsu, Tetsuro Oishi, Hiroaki Itamochi, Mayumi Sawada, Michiko Nonaka, Seiya Sato, Jun Chikumi, Shinya Sato, Muneaki Shimada, Tasuku Harada. Serum VEGF-A may predict prognosis in patients with epithelial ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3387.

Abstract 5298: Serum angiogenic factors may predict prognosis in patients with epithelial ovarian cancer

Objective: Angiogenesis is one of the processes that is critical for the growth, invasion and metastasis of solid tumors, including epithelial ovarian cancer (EOC). The vascular endothelial growth factor (VEGF) family is one of the major pathways involved in tumor angiogenesis, and VEGF expression is activated by hypoxia-inducible factor (HIF)-1α. The aim of this study was to determine whether serum levels of these angiogenic factors could be used as prognostic biomarkers in patients with EOC. Methods: A total of 133 patients with EOC who were treated at Tottori University Hospital between 2006 and 2012 were enrolled in this study. The study was approved by the Institutional Review Board of the School of Medicine of Tottori University. All patients gave written informed consent before the collection of specimens according to institutional guidelines. Serum samples were collected before initial surgery and levels of VEGF-A, -C and HIF-1α were analyzed by enzyme-linked immunosorbent assay (ELISA). We evaluated the association between the levels of VEGF-A, -C, and HIF-1α and clinicopathologic variables. We also determined the protein expression of VEGF-A, -C, and HIF-1α by immunohistochemical staining in paraffin-embedded tumors from EOC patients Results: The protein expressions of VEGF-A, -C, and HIF-1α were strongly observed in the cancer cells. Median levels of serum VEGF-A, -C and HIF-1α were 280, 4866 and 125 pg/ml, respectively. The levels of VEGF-A in patients at stage IV were significantly higher than those in patients at stage I. Both histologic subtypes and lymph node involvement were not related to levels of these angiogenic factors. We found a significant positive correlation between VEGF-A levels and the ascitic volume. The overall survival rate was significantly lower in FIGO stage III or IV patients with EOC. We set the cutoff value of these factors at the median levels of each angiogenic factors. The 5-year survival rate for patients with high VEGF-A levels was significantly lower than those with low levels (61.7% vs. 41.8%, P = 0.0147). Both HIF-1α and VEGF-C levels were not related to outcome of patients. Multivariate analysis revealed that serum VEGF-A level and FIGO stage were independent prognostic factors. Conclusion: These results suggest that serum VEGF-A may be a promising prognostic biomarker for EOC. Citation Format: HIROAKI KOMATSU, Tetsuro Oishi, Hiroaki Itamochi, Akiko Kudoh, Michiko Nonaka, Seiya Sato, Jun Chikumi, Shinya Sato, Muneaki Shimada, Junzo Kigawa, Tasuku Harada. Serum angiogenic factors may predict prognosis in patients with epithelial ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5298. doi:10.1158/1538-7445.AM2015-5298