Molecular Diagnostics in Dual Site Ovarian and Endometrial Cancers. S.J. Ramus¹, K. Elmasry¹, J. Whittaker², Z. Luo³, A. Gammerman³, N. Singh⁴, W.G. McCluggage⁵, A. Ayhan⁶, K. Lu⁷, I.J. Jacobs¹, S.A. Gayther¹. 1) Dept Gynaecological Oncology, University College London, UK; 2) London School of Hygiene & Tropical Medicine, UK; 3) Royal Holloway, University of London, UK; 4) St.Bartholomew`s and The Royal London, UK; 5) Royal Victoria Hospital, Belfast, UK; 6) Seirei Mikatahara Hospital, Japan; 7) MD Anderson Cancer Center, USA.
   Five to eight percent of patients undergoing laparotomy for suspected ovarian malignancies are found to have synchronous tumours of the ovary and endometrium. Patients with dual primary (DP) tumours have a better prognosis than a single primary tumour with metastasis (SPWM). The benefits of a correct diagnosis include the individualisation of patient management, the avoidance of unnecessary treatment and a more accurate prognosis. Currently, the distinction between DP and SPWM involves pathological interpretation and there is often uncertainty when the tumours have the same histological subtype. We have established a collection of 90 synchronous ovarian and endometrial tumours, in which tumour pairs have the same histological subtype. We have developed a molecular genetic test to distinguish between DP and SPWM cases, based on the analysis of microsatellite markers for allelic imbalance and microsatellite instability at 22 microsatellite markers. We compared genetic data with working pathology diagnoses and detailed histopathology review. Of the 39 patients previously diagnosed as DP cases, 31 had the same results for pathology and genetic tests. A further 7 cases were not informative and one case was given a diagnosis of SPWM. Of 25 patients diagnosed as SPWM by pathology, genetic tests identified 17 as SPWM and 3 as not informative. Significantly, 5 cases previously thought to be SPWM by pathology were diagnosed as DP by genetics suggesting these cases may have had more rigorous adjuvant chemotherapy than necessary. There were 26 patients in this study for whom a diagnosis by pathology was uncertain. Genetics analyses diagnosed 20 of these cases as DP, 4 as SPWM and 2 were uninformative. These data indicate that genetic methods can be used as powerful tools to complement existing histopathology for the diagnosis of synchronous cancers.