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

A RISK MODEL FOR SECONDARY CYTOREDUCTIVE SURGERY IN RECURRENT OVARIAN CANCER: AN EVIDENCE-BASED PROPOSAL FOR PATIENT SELECTION

Background: To develop a risk model for predicting complete secondary cytoreductive surgery (SCR) in patients with recurrent ovarian cancer. Methods: Individual data of 1075 patients with recurrent ovarian cancer undergoing SCR from seven world-wide centers were pooled and analyzed. The risk model was developed based on the factors impacting on SCR surgical outcome. Additional data on 117 patients who were not included in the development of the model were used for external validation and to assess the discrimination of the model. Results: Of the 1075 patients, 434 (40.4%) underwent complete resection. Complete secondary cytoreduction was associated with six variables: FIGO stage (OR=1.32, 95%CI: 0.97-1.80), residual disease after primary cytoreduction (OR=1.69, 95%CI: 1.26-2.27), progression-free interval (OR=2.27, 95%CI: 1.71-3.01), ECOG performance status (OR=2.23, 95%CI: 1.45-3.44), CA125 (OR=1.85, 95%CI: 1.41-2.44) and ascites at recurrence(OR=2.79, 95%CI: 1.88-4.13). These variables were entered into the risk model and assigned scores ranging from 0 to 11.9. Patients with total scores of 0-4.7 were categorized as the low risk group, in which the proportion of complete cytoreduction was 53.4% compared to 20.1% in the high risk group (OR=4.55, 95%CI: 3.43-6.04). In external validation, the sensitivity and specificity was 83.3% and 57.6%, respectively. Area under the curve of the receiveroperating characteristics for predicting complete SCR was 0.68 (95%CI: 0.60-0.79). Conclusions: This model and scoring system may well predict the outcome of SCR and could potentially be useful in future clinical trials to determine which patients with recurrent ovarian cancer should have SCR as part of their management

A risk model for secondary cytoreductive surgery in recurrent ovarian cancer: An evidence-based proposal for patient selection.

Background: To develop a risk model for predicting complete secondary cytoreductive surgery (SCR) in patients with recurrent ovarian cancer. Methods: Individual data of 1075 patients with recurrent ovarian cancer undergoing SCR from seven world-wide centers were pooled and analyzed. The risk model was developed based on the factors impacting on SCR surgical outcome. Additional data on 117 patients who were not included in the development of the model were used for external validation and to assess the discrimination of the model. Results: Of the 1075 patients, 434 (40.4%) underwent complete resection. Complete secondary cytoreduction was associated with six variables: FIGO stage (OR=1.32, 95%CI: 0.97-1.80), residual disease after primary cytoreduction (OR=1.69, 95%CI: 1.26-2.27), progression-free interval (OR=2.27, 95%CI: 1.71-3.01), ECOG performance status (OR=2.23, 95%CI: 1.45-3.44), CA125 (OR=1.85, 95%CI: 1.41-2.44) and ascites at recurrence(OR=2.79, 95%CI: 1.88-4.13). These variables were entered into the risk model and assigned scores ranging from 0 to 11.9. Patients with total scores of 0-4.7 were categorized as the low risk group, in which the proportion of complete cytoreduction was 53.4% compared to 20.1% in the high risk group (OR=4.55, 95%CI: 3.43-6.04). In external validation, the sensitivity and specificity was 83.3% and 57.6%, respectively. Area under the curve of the receiveroperating characteristics for predicting complete SCR was 0.68 (95%CI: 0.60-0.79). Conclusions: This model and scoring system may well predict the outcome of SCR and could potentially be useful in future clinical trials to determine which patients with recurrent ovarian cancer should have SCR as part of their management

Maximal cytoreductive effort in epithelial ovarian cancer surgery

The surgical management of advanced epithelial ovarian cancer involves cytoreduction, or removal of grossly-evident tumor. Residual disease after surgical cytoreduction of ovarian cancer has been shown to be strongly associated with survival. The goal of surgery is "optimal" surgical cytoreduction, which is generally defined as residual disease of 1 cm or less. However, the designation of "optimal" surgical cytoreduction has evolved to include maximal surgical effort and no gross residual disease. In order to achieve this, more aggressive surgical procedures such as rectosigmoidectomy, diaphragm peritonectomy, partial liver resection, and video-assisted thoracic surgery are reported and increasingly utilized in the surgical management of advanced ovarian cancer. The role of maximal surgical effort also extends to the recurrent setting where the goal of surgery should be complete cytoreduction. Patient selection is important in identifying appropriate candidates for surgical cytoreduction in the recurrent setting. The purpose of this article is to review the role of maximum surgical effort in primary and recurrent ovarian cancer