SO23: Renal cell carcinoma in Lynch Syndrome: a preliminary report from a Mallorca group collaborative study

Martina Calicchia1, Toni Seppala2, Jukka-Pekka Mecklin3, Frederick J Hes4, Maartje Nielsen4, Gareth D Evans5, Elke Holinski-Feder6, Monika Morak6, Brigitte Royer-Pokora7, Marta Pineda8, Gabriel Capella8, Lone Sunde9, Christina Therkildsen10, Pål Møller11, Emanuela Lucci-Cordisco1, Maurizio Genuardi1.

1 – Institute of Medical Genomics, Catholic University Faculty of Medicine, Rome, Italy. 2 – Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland. 3 – Department of Education and Science, Central Finland Health Care District, Jyväskylä, and University of Eastern Finland, Finland. 4 – Department of Clinical Genetics, Leiden University Medical Center, RC Leiden, The Netherlands. 5 – Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK. 6 – Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, and Medizinisch Genetisches Zentrum, Munich, Germany. 7 – Medical Faculty, Institute of Human Genetics and Anthropology, Heinrich-Heine University , Düsseldorf , Germany. 8 – Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Spain. 9 – Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark. 10 – HNPCC Register, Clinical Research Center, Copenhagen University Hospital, Hvidovre, Denmark. 11 – Research Group Inherited Cancer, Department of Medical Genetics, and Department of Tumour Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Norway.


Lynch syndrome (LS) is associated with increased risk of several extraintestinal cancers, including urothelial cancer. It is not clear whether LS patients are also at increased risk of renal cell carcinoma (RCC).


In order to determine if there is a link between RCC and LS, we have started a collaborative European study to collect information on the clinical, pathological, molecular and immunohistochemical characteristics of RCC associated with LS.


So far, data on 35 cases have been accrued, with the following results: 17 males, 18 females; mean age at diagnosis 60 years (range 45-78); involved gene: 10 MSH2, 19 MLH1, 5 MSH6, 1 PMS2; histology: 24 clear cell, 3 papillary type 1, 2 papillary type 1, 1 papillary type not specified; 10 cases tested for MSI, of these 7 were MSS and 3 MSI-H; all 11 cases tested for MMR protein immunohistochemistry showed loss of MMR protein signals: 6 MLH1 or MLH1/PMS2, 3 loss of MSH2/MSH6, and 2 loss of MSH6 only.


These results indicate that RCC arising in the context of LS is associated with evidence of MMR disruption (immunohistochemical loss variably associated with MSI). Further data submissions and collaborations are encouraged.