Immunohistochemical expression of VEGF predicts response to platinum based chemotherapy in patients with epithelial ovarian cancer.

PURPOSE: For patients with epithelial ovarian cancer (EOC) cytoreduction, with a combination of taxane and platinum, is the standard of care. Despite this, approximately 50% of patients with advanced disease will relapse and moreover 15-20% of cases of EOC are resistant to platinum based chemotherapy. Vascular Endothelial Growth Factor (VEGF), an angiogenic factor, is associated with poor prognosis. This study was undertaken to examine whether there is an association between VEGF-A expression in the tumour of EOC patients and their response to platinum based chemotherapy. METHODS: The study cohort consisted of 66 patients with advanced stage EOC (FIGO III-IV). Ovarian cancer tissue was analysed for VEGF-A expression immunohistochemically. Protein expression was measured and correlated, with platinum sensitivity and overall patient survival. RESULTS: Median age of patients was 53 years, 45 patients had platinum sensitive disease (68%), the remaining patients being platinum resistant (32%). Of the platinum resistant group, 18 (86%) patients had high VEGF score compared to only 1 (2%) with high VEGF score in the platinum sensitive group. Median survival was 11 months in the patient group with high VEGF score versus 32 months in that cohort with low VEGF score. VEGF expression was significantly inversely correlated with overall survival (P < 0.0001). CONCLUSION: We demonstrated that tumours of patients with platinum resistant EOC exhibit higher levels of VEGF expression compared to the platinum sensitive group. VEGF in EOC, may be of clinical and therapeutic relevance and suggests a role for first line anti-angiogenic therapy.

Prognostic significance of intratumoral vascular endothelial growth factor as a marker of tumour angiogenesis in epithelial ovarian cancer.

OBJECTIVES: The aim of this study was to examine the prognostic significance of vascular endothelial growth factor (VEGF) in epithelial ovarian cancer (EOC). METHODS: Surgical specimens of 105 patients with primary EOC FIGO Stages 1 to 4, who underwent surgical staging, were investigated. Expression of VEGF was evaluated by immunohistochemical staining using related monoclonal antibodies. The correlation of this data with survival and established prognostic factors such as histological grade, FIGO stage and residual tumour status was evaluated. Multivariate analysis and correlation tests were performed. RESULTS: The results of VEGF expression were correlated with clinicopathological variables and overall survival. No correlation between the VEGF expression and clinicopathological factors was identified. However, VEGF expression was found to be significantly correlated to survival, and a prognostic factor independent of the stage of disease and residual tumour status (p < 0.0001). CONCLUSION: High intratumoral VEGF expression, a marker of angiogenesis, appeared to be an independent prognostic factor for overall survival in women with EOC. Angiogenic evaluation of patients with EOC may play a role in predicting a subgroup of patients with aggressive disease. These patients could be the target of front-line molecular targeted therapy with anti-angiogenic agents.

Strategies for endometrial screening in the Lynch syndrome population: a patient acceptability study.

Lynch syndrome is an autosomal dominant syndrome accounting for 2-5% of all colorectal cancer. In addition, women with Lynch syndrome have a substantially increased risk of developing endometrial cancer particularly pre-menopausally when symptom detection is more difficult. Current recommendations are that screening for endometrial cancer be offered to women identified to be at risk. The aim of the study was to assess the relative patient acceptability of the available screening modalities. A survey of the perception of the associated pain or discomfort associated with different screening modalities was conducted. Transvaginal ultrasonography was associated with less discomfort than hysteroscopy or Pipelle biopsy, and would be the single test of choice for the majority. There was no significant difference between the pain scores for hysteroscopy and Pipelle biopsy. Issues relating to test acceptability specific to this population are described. Patient acceptability of screening modalities should form an integral part of studies assessing the effectiveness of endometrial screening in the Lynch syndrome population.

Views of BRCA gene mutation carriers on preimplantation genetic diagnosis as a reproductive option for hereditary breast and ovarian cancer.

BACKGROUND: In May 2006, the UK Human Fertilization and Embryology Authority (HFEA) approved use of preimplantation genetic diagnosis (PGD) for lower penetrance, late onset cancer susceptibility syndromes such as hereditary breast and ovarian cancer (HBOC). This is the first report on views of BRCA gene mutation carriers on use of PGD for HBOC. METHODS: Between December 2005 and February 2006, a postal survey of BRCA mutation carriers attending a Familial Cancer Clinic was undertaken. RESULTS: Of 102 women sent questionnaires, 52 (51%) responded. Thirty-nine (75%) felt it was acceptable to offer PGD for HBOC. Fifteen (37.5%) of 40 who had completed their families would personally have considered PGD if it had been available. Only one of seven (14%) contemplating a future pregnancy would consider PGD. Eighteen (35%) wrote extensively about their concerns including increasing availability of effective treatment and good quality of life. CONCLUSIONS: The majority of BRCA gene mutation carriers are supportive of offering PGD to others, thus endorsing the HFEA decision. However, most women would not consider it personally. Concerns raised highlight the need for regular HFEA reviews of the licensing criteria, as HBOC may cease to be a "serious life threatening illness" in the future.