These consensus statements were developed by the European Society for Medical Oncology (ESMO) and the European Society of Gynaecological Oncology (ESGO) and are published jointly in the Annals of Oncology and the International Journal of Gynecological Cancer. The two societies nominated participants who attended the consensus conference and co-authored the final manuscript. ‡ See Appendix for members of the ESMO-ESGO Ovarian Cancer Consensus Conference Working Group. The development of guidelines recommendations is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based recommendations in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO-ESGO consensus conference on ovarian cancer was held on 12-14 April 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage disease and recurrent disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO-ESGO consensus conference, together with a summary of evidence supporting each recommendation.
BACKGROUND It was demonstrated previously that the Snail family of transcription factors and Smad‐interacting protein 1 (Sip1) regulate E‐cadherin and matrix metalloproteinase 2 (MMP‐2) expression, cellular morphology, and invasion in carcinoma. For the current study, the authors analyzed the relation between the expression of Snail, Slug, and Sip1; the expression of MMP‐2 and E‐cadherin; and clinical parameters in patients with metastatic ovarian and breast carcinoma. METHODS One hundred one fresh‐frozen, malignant effusions from patients who were diagnosed with gynecologic carcinomas (78 ovarian carcinomas and 23 breast carcinomas) were studied for mRNA expression of Snail, Slug, Sip1, MMP‐2, and E‐cadherin using reverse transcriptase‐polymerase chain reaction analysis. Snail mRNA and E‐cadherin protein expression levels also were studied in ovarian carcinoma effusions using in situ hybridization and immunocytochemistry. The results were analyzed for possible correlation with clinicopathologic parameters in both tumor types. RESULTS E‐cadherin mRNA expression was lower in breast carcinoma (P = 0.001), whereas Snail expression was higher (P = 0.003). The Snail/E‐cadherin ratio (P < 0.001) and the Sip1/E‐cadherin ratio (P = 0.002) were higher in breast carcinomas. Sip1 mRNA expression (P < 0.001) and Slug mRNA expression (P < 0.001) were correlated with the expression of MMP‐2 in ovarian carcinomas. The Sip1/E‐cadherin ratio was higher in primary ovarian carcinomas at the time of diagnosis compared with postchemotherapy ovarian carcinoma effusions (P = 0.003), higher in Stage IV tumors compared with Stage III tumors (P = 0.049), and higher in pleural effusions compared with peritoneal effusions (P = 0.044). In a univariate survival analysis of patients with ovarian carcinoma, a high Sip1/E‐cadherin ratio predicted poor overall survival (P = 0.018). High E‐cadherin mRNA expression predicted better disease‐free survival (P = 0.023), with a similar trend for a low Slug/E‐cadherin ratio (P = 0.07). High Snail mRNA expression predicted shorter effusion‐free survival (P = 0.008), disease‐free survival (P = 0.03), and overall survival (P = 0.008) in patients with breast carcinoma. CONCLUSIONS Transcription factors that regulate E‐cadherin were expressed differentially in metastatic ovarian and breast carcinoma. Snail may predict a poor outcome in patients who have breast carcinoma metastatic to effusions. E‐cadherin expression generally was conserved in effusions from patients with ovarian carcinoma, but the subset of patients with postulated Sip1‐induced repression of this adhesion molecule had a significantly worse outcome. This finding was in agreement with the stronger suppression of E‐cadherin by Snail and Sip1 in breast carcinoma effusions, a clinical condition associated with extremely poor survival. Cancer 2005. © 2005 American Cancer Society.
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