Gene expressions and copy numbers associated with metastatic phenotypes of uterine cervical cancer

BACKGROUND: A better understanding of the development of metastatic disease and the identification of molecular markers for cancer spread would be useful for the design of improved treatment strategies. This study was conducted to identify gene expressions associated with metastatic phenotypes of locally advanced cervical carcinomas and investigate whether gains or losses of these genes could play a role in regulation of the transcripts. Gene expressions and copy number changes were determined in primary tumors from 29 patients with and 19 without diagnosed lymph node metastases by use of cDNA and genomic microarray techniques, respectively. RESULTS: Thirty-one genes that differed in expression between the node positive and negative tumors were identified. Expressions of eight of these genes (MRPL11, CKS2, PDK2, MRPS23, MSN, TBX3, KLF3, LSM3) correlated with progression free survival in univariate analysis and were therefore more strongly associated with metastatic phenotypes than the others. Immunohistochemistry data of CKS2 and MSN showed similar relationships to survival. The prognostic genes clustered into two groups, suggesting two major metastatic phenotypes. One group was associated with rapid proliferation, oxidative phosphorylation, invasiveness, and tumor size (MRPS23, MRPL11, CKS2, LSM3, TBX3, MSN) and another with hypoxia tolerance, anaerobic metabolism, and high lactate content (PDK2, KLF3). Multivariate analysis identified tumor volume and PDK2 expression as independent prognostic variables. Gene copy number changes of the differentially expressed genes were not frequent, but correlated with the expression level for seven genes, including MRPS23, MSN, and LSM3. CONCLUSION: Gene expressions associated with known metastatic phenotypes of cervical cancers were identified. Our findings may indicate molecular mechanisms underlying development of these phenotypes and be useful as markers of cancer spread. Gains or losses of the genes may be involved in development of the metastatic phenotypes in some cases, but other mechanisms for transcriptional regulation are probably important in the majority of tumors

PREDICTORS OF SURVIVAL IN PATIENTS WITH RECURRENT OVARIAN CANCER UNDERGOING SECONDARY CYTOREDUCTIVE SURGERY BASED ON AN INTERNATIONAL COLLABORATIVE ANALYSIS

PREDICTORS OF SURVIVAL IN PATIENTS WITH RECURRENT OVARIAN CANCER UNDERGOING SECONDARY CYTOREDUCTIVE SURGERY BASED ON AN INTERNATIONAL COLLABORATIVE ANALYSIS R.-Y. Zang1, P. Harter2, D.S. Chi3, J. Sehouli4, R. Jiang1, C.G. Tropé5, A. Ayhan6, G. Cormio7, Y. Xing8, K. Wollschlaeger9, E.I. Braicu4, C.A. Rabbitt3, H. Oksefjell5, W.-J. Tian1, C. Fotopoulou4, J. Pfisterer10, A. du Bois2, J.S. Berek11 1Ovarian Cancer Program, Department of Gynecologic Oncology, Fudan University Cancer Hospital, Shanghai, China, 2Department of Gynecology & Gynecologic Oncology, HSK, Dr. Horst Schmidt Klinik, Wiesbaden, Germany, 3Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 4Department of Gynecology, Charité Medical University of Berlin, Berlin, Germany, 5Division of Gynecology and Obstetrics, Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway, 6Department of Obstetrics and Gynecology, Baskent University Faculty of Medicine, Ankara, Turkey, 7Department of Gynecology, Obstetrics and Neonatology, University of Bari, Bari, Italy, 8Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 9Department of Gynecology and Obstetrics, University of Magdeburg, Magdeburg, 10Department of Gynecology and Obstetrics, Hospital Solingen, Solingen, Germany, 11Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA, USA Background: This study aims to identify prognostic factors and to develop a risk model predicting survival in patients undergoing secondary cytoreductive surgery (SCR) for recurrent epithelial ovarian cancer. Methods: Individual data of 1,100 patients with recurrent ovarian cancer of a progression-free interval at least 6 months who underwent SCR were pooled analyzed. A simplified scoring system for each independent prognostic factor was developed according to its coefficient. Internal validation was performed to assess the discrimination of the model. Results: Complete SCR was strongly associated with the improvement of survival, with a median survival of 57.7 months, when compared to 27.0 months in those with residual disease of 0.1-1cm and 15.6 months in those with residual disease of >1cm, respectively (P< 0.0001). Progression-free interval (< 23.1 months vs. >=23.1 months, hazard ratio (HR),1.72; score: 2), ascites at recurrence (present vs. absent, HR, 1.27; score: 1), extent of recurrence (multiple vs. localized disease, HR, 1.38; score: 1) as well as residual disease after SCR (R1 vs. R0, HR, 1.90, score: 2; R2 vs. R0, HR,3.0, score: 4) entered into the risk model. Conclusion: This prognostic model may provide evidence to predict survival benefit from secondary cytoreduction in patients with recurrent ovarian cancer