2008 Summer Meeting - Leeds - The Pathological Society of Great ...

O33Molecular Genetic Profiling of Ovarian Clear CellAdenocarcinomasDSP Tan 1,2 ,MIravani 1 , B Mahler-Araujo 1 , MBK Lambros 1 ,R Natrajan 1 ,NTamber 1 , K Fenwick 1 ,AMackay 1 , C Jameson 3 ,A Williams 4 ,WG McClugage 5 ,MEl-Bahrawy 6 , A Ashworth 1 ,SB Kaye 2 , JS Reis-Filho 11 The Breakthrough Breast Cancer Research Centre, Institute of CancerResearch, London, 2 Section of Medicine, Institute of Cancer Research,Royal Marsden Hospital, Sutton, Surrey, 3 Department of Pathology RoyalMarsden Hospital, London, 4 Department of Pathology, University ofEdinburgh, Edinburgh, 5 Department of Pathology, Royal Group ofHospitals Trust, Belfast, 6 Imperial College School of Medicine,Hammersmith Hospital, LondonOvarian clear cell adenocarcinomas (OCCAs) are relatively resistant toplatinum-based chemotherapy and associated with a poorer prognosis whencompared to other subtypes of ovarian cancer. Hence, the identification oftherapeutic targets for OCCAs would be invaluable. To characterise themolecular genetic profiles of OCCAs and identify potential therapeutic targets,the genetic profiles of 52 OCCA tumours were analysed using a 32K tiling-pathmicroarray CGH (aCGH) platform. Genome-wide aCGH analysis revealed thatOCCAs could be classified into “simplex” (62%), “complex” (23%) and“amplifier” (15%). Recurrent amplifications (in >20% of OCCAs) included1p36.32, 8q24.21, 8q24.3, 10q26.3, 17q25.3, 19p13.3, 20q13.33, and 21q22.3.Of particular interest is a region of recurrent amplification on 20q13.33 with afrequency of 50%. The smallest region of overlap within this amplicon maps toa 543kb region on chromosome 20q13.33 between 61178kb to 61721kb andincludes YTHDF1, BIRC7, ARFGAP1, COL20A1, EEF1A2, PTK6, SRMS,PDIP1 and GMEB2. We are currently optimising in house generatedchromogenic in situ hybridisation probes to validate this amplicon in a largerseries of OCCAs. Amplification and overexpression of PTK6 has beendescribed in high-grade serous ovarian carcinomas and is associated with a poorprognosis, while expression of the antiapoptotic BIRC7/Livin gene is associatedwith chemoresistance in renal clear cell carcinomas. Our study provides the firsthigh-resolution molecular genetic analysis of OCCA tumours and identifiesputative amplicon drivers that may be exploited as therapeutic targets.O34Pure Salivary Duct Carcinomas Can Be Classified IntoLuminal, Her2 and Basal-Like PhenotypesSDi Palma 1 , A Skalova 2 ,MUngari 3 , A Sandison 4 , R Simpson 5 ,C Marchio 6 , JS Reis-Filho 61 Department of Pathology, Royal Surrey County Hospital, PGMS,University of Surrey, Guildford, Surrey, 2 Department of Pathology,Medical Faculty Hospital, Charles University, Plzen, Czech Republic,3 Department of Pathology, Spedali Civili Brescia, Italy, 4 Department ofHistopathology, Imperial College Healthcare Trust, Charing CrossHospital, London, 5 Department of Pathology, Royal Devon and ExeterHospital, Exeter, Devon, 6 The Breakthrough Breast Cancer ResearchCentre, Institute of Cancer Research, LondonSalivary duct carcinomas and invasive ductal carcinomas of the breast havesimilar morphological features. It has recently been demonstrated that invasivebreast cancers can be subclassified into luminal, HER2 and basal-like cancersand that these groups have distinct molecular characteristics and clinicalbehaviour. The aim of this study was to apply an immunohistochemical panelpreviously validated for breast cancer to determine whether salivary ductcarcinomas could also be classified into these similar molecular groups (i.e.luminal, HER2 and basal-like). 27 pure salivary duct carcinomas were reviewedby one of the authors, typed and graded according to the WHO classification,and stained with antibodies against oestrogen receptor (ER), androgen receptor(AR), HER2, epidermal growth factor receptor (EGFR) and cytokeratin (Ck)5/6. Cases were classified as of HER2 phenotype if they expressed HER2 3+.HER2 negative cases were classified as of ‘luminal’ phenotype if positive forER or AR. Cases that lacked HER2, ER/ AR and expressed EGFR and/or Ck5/6 were considered of ‘basal-like’ phenotype. Cases lacking all markers wereconsidered of indeterminate phenotype. 15% were of HER2 phenotype, 70%were of luminal phenotype, 3% were of basal-like phenotype and 11% were ofindeterminate phenotype. In a way akin to breast cancer, salivary ductcarcinomas can also be classified according to the molecular subgroups. Mostimportantly, we report for the first time the existence of a subgroup of puresalivary duct carcinomas that have the typical immunohistochemical profile of‘basal-like’ carcinomas.86 Summer Meeting (194 th ) 1–4 July 2008 Scientific Programme