1. Collaborative Study Proposal: Renal Cell Cancer in Lynch Syndrome

2. Background Several reports of synchronous or metachronous RCC and CRC Not statistically significant for RCCs overall Significant association with papillary RCC 1 Familial association in population based study 2 Increased risk in 2 registry- based series – SIR 4.7 (1-14) 1 – SIR 11.22 (2.31-32.79) (2 RCC + 1 R pelvis) 2 Mean age at dx: 74 (47-88) yrs Histology: – 4 “adenocarcinoma” 3 – 1 tubulopapillary 4 MSI: 1/5 MSI-H 4,5 IHC: loss in 3 5, no loss in 1 4 1 Thompson et al. 2006; 2 Hemminki and Chen 2004 1 Aarnio et al. 1999; 2 Win et al. 2012; 3 Aarnio et al. 2012; 4 Mongiat-Artus et al. 2006; 5 Gylling et al. 2008 RCC AND CRCRCC IN LS

3. Renal cell carcinomas in Florence LS patients PT (SEX) MUTATIONCANCERS (YRS AT DX) RCC HISTOLOGY MSI STATUSIHC 4 (M)MLH1 c.301G>A p.Gly101Ser -Urether (51) -Colon (61) -Colon (66) -Kidney (67) -Urether (67) Clear cellMSSMLH1- MSH2+ MSH6+ 8 (M)MSH2 Exon 7 deletion -Colon (48) -Kidney (59) Papillary type 2MSSMLH1+ MSH2- MSH6- 9 (F)MLH1 c.2181_2182delCA p.His727fsx5 -Colon (29) -Colon (55) -Kidney (58) Clear cellMSSMLH1- MSH2+ MSH6+

4. PROPOSAL: EVALUATION OF CLINICAL AND MOLECULAR CHARACTERISTICS OF RCC ASSOCIATED WITH LYNCH SYNDROME 1.Age and sex 2.Histology 3.Detection (sympt. /screening/incidental) 4.MSI 5.IHC 6.Tumor DNA for other studies (i.e. VHL mutations, 3p loss, array-CGH) 4-5-6 can be performed in Rome if requested