Jason D. Wright

Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression.

Recurrent karyotypic abnormalities are a characteristic feature of cervical cancer (CC) cells, which may result in deregulated expression of important genes that contribute to tumor initiation and progression. To examine the role of gain of the long arm of chromosome 20 (20q), one of the common chromosomal gains in CC, we evaluated CC at various stages of progression using single nucleotide polymorphism (SNP) array, gene expression profiling, and fluorescence in situ hybridization (FISH) analyses. This analysis revealed copy number increase (CNI) of 20q in >50% of invasive CC and identified two focal amplicons at 20q11.2 and 20q13.13 in a subset of tumors. We further demonstrate that the acquisition of 20q gain occurs at an early stage in CC development and the high‐grade squamous intraepithelial lesions (HSIL) that exhibit 20q CNI are associated (P = 0.05) with persistence or progression to invasive cancer. We identified a total of 26 overexpressed genes as consequence of 20q gain (N = 14), as targets of amplicon 1 (N = 9; two genes also commonly expressed with 20q gain) and amplicon 2 (N = 6; one gene also commonly expressed with 20q gain). These include a number of functionally important genes in cell cycle regulation (E2F1, TPX2, KIF3B, PIGT, and B4GALT5), nuclear function (CSEL1), viral replication (PSMA7 and LAMA5), methylation and chromatin remodeling (ASXL1, AHCY, and C20orf20), and transcription regulation (TCEA2). Our findings implicate a role for these genes in CC tumorigenesis, represent an important step toward the development of clinically significant biomarkers, and form a framework for testing as molecular therapeutic targets.

Contemporary management of endometrial cancer.

The treatment of endometrial cancer has changed substantially in the past decade with the introduction of a new staging system and surgical approaches accompanied by novel adjuvant therapies. Primary surgical treatment is the mainstay of therapy but the effectiveness and extent of lymphadenectomy has been challenged, and its acceptance as a routine procedure varies by country. The role of radiation has evolved and chemotherapy has been incorporated, either alone or combined with radiation, to treat the many patients in whom cancer recurs because of a tumour outside the originally radiated pelvic and lower abdominal area. Use of traditional adjuvant chemotherapeutics has been challenged in clinical trials of new agents with improved side-effect profiles. Novel agents and targeted therapies are being investigated. Research into genetic susceptibility to endometrial cancer and the potential genetic aberrations that might translate into therapeutic interventions continues to increase. Substantial global variability in the treatment of endometrial cancer has led to examination of long-accepted norms, which has resulted in rapidly changing standards. International cooperation in clinical trials will hasten progress in treatment of this ubiquitous cancer.

Comparative Performance of the 2009 International Federation of Gynecology and Obstetrics' Staging System for Uterine Corpus Cancer.

OBJECTIVE: To perform a population-based analysis comparing the performance of the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) staging systems. METHODS: Women with endometrioid adenocarcinoma of the uterus treated between 1988 and 2006 and recorded in the Surveillance, Epidemiology, and End Results database were analyzed. Women were classified based on 1988 and 2009 FIGO staging systems. Major changes in the 2009 system include: 1) classification of patients with stage IA and IB tumors as stage IA; 2) elimination of stage IIA; and 3) stratification of stage IIIC into pelvic nodes only (IIIC1) or paraaortic nodal (IIIC2) involvement. Survival and use of adjuvant therapy were analyzed. RESULTS: A total of 81,902 women were identified. Based on the 1988 staging system, survival for stage IA was 90.7% (95% confidence interval [CI], 90–91%) compared with 88.9% (95% CI 88–89%) for IB tumors. In the 2009 system, survival was 89.6% (95% CI 89–90%) for stage IA and 77.6% (95% CI 76–79%) for stage IB. The survival for FIGO 1988 stage IIA was superior to stage IC, whereas in the 2009 system, survival for stage II was inferior to all stage I patients. The newly defined stage IIIC substages are prognostically different. Survival for stage IIIC1 was 57.0% (95% CI 54–60%) compared with 49.4% (95% CI 46–53%) for stage IIIC2. CONCLUSION: The 2009 FIGO staging system for uterine corpus cancer is highly prognostic. The reduction in stage I substages and the separation of stage III will further clarify important prognostic features. LEVEL OF EVIDENCE: III

Bevacizumab combination therapy in recurrent, platinum-refractory, epithelial ovarian carcinoma: A retrospective analysis.

The study was undertaken to determine the safety and efficacy of the monoclonal, antivascular endothelial growth factor antibody bevacizumab in combination with cytotoxic chemotherapy for women with platinum‐refractory ovarian cancer.

Utility of parametrectomy for early stage cervical cancer treated with radical hysterectomy

Removal of the parametrial soft tissue is recommended for patients with cervical cancer undergoing radical hysterectomy. Parametrectomy results in significant morbidity. The objective of the study was to determine factors predictive of parametrial tumor spread and to define a subset of patients at low risk for parametrial disease.

Comparative Effectiveness of Robotic Versus Laparoscopic Hysterectomy for Endometrial Cancer

PURPOSE Use of robotics in oncologic surgery is increasing; however, reports of safety and efficacy are from highly experienced surgeons and centers. We performed a population-based analysis to compare laparoscopic hysterectomy and robotic hysterectomy for endometrial cancer. PATIENTS AND METHODS The Perspective database was used to identify women who underwent a minimally invasive hysterectomy for endometrial cancer from 2008 to 2010. Morbidity, mortality, and cost were evaluated using multivariable logistic and linear regression models. RESULTS We identified 2,464 women, including 1,027 (41.7%) who underwent laparoscopic hysterectomy and 1,437 (58.3%) who underwent robotic hysterectomy. Women treated at larger hospitals, nonteaching hospitals, and centers outside of the northeast were more likely to undergo a robotic hysterectomy procedure, whereas black women, those without insurance, and women in rural areas were less likely to undergo a robotic hysterectomy procedure (P < .05 for all). The overall complication rate was 9.8% for laparoscopic hysterectomy versus 8.1% for robotic hysterectomy (P = .13). The adjusted odds ratio (OR) for any morbidity for robotic hysterectomy was 0.76 (95% CI, 0.56 to 1.03). After adjusting for patient, surgeon, and hospital characteristics, there were no significant differences in the rates of intraoperative complications (OR, 0.68; 95% CI, 0.42 to 1.08), surgical site complications (OR, 1.49; 95% CI, 0.81 to 2.73), medical complications (OR, 0.64; 95% CI, 0.40 to 1.01), or prolonged hospitalization (OR, 0.85; 95% CI, 0.64 to 1.14) between the procedures. The mean cost for robotic hysterectomy was

Racial disparities for uterine corpus tumors: changes in clinical characteristics and treatment over time.

10,618 versus

Prognostic significance of adenocarcinoma histology in women with cervical cancer

8,996 for laparoscopic hysterectomy (P < .001). In a multivariable model, robotic hysterectomy was significantly more costly (

Center of excellence for placenta accreta

1,291; 95% CI,

Comparative Effectiveness Research in Oncology Methodology: Observational Data

985 to