Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

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  • Slide 1
  • Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Universit dellAquila Focus on Endocrine Neoplasia, Roma, Luglio 2010
  • Slide 2
  • McGlynn, J Clin Oncol 2005 GCT E il tumore maschile pi diffuso nelle fascia di et tra i 15 ed i 45 anni EPIDEMIOLOGIA
  • Slide 3
  • Rejpert-De-Meyts, Ann NY Acad Sci1120, 2007 GCT EPIDEMIOLOGIA
  • Slide 4
  • TESTIS CANCER INCIDENCE RATE IN EUROPE Differenze etnico- geografiche -fattori ambientali ? -fattori genetici ?
  • Slide 5
  • Immigration studies indicate potential environmental factors acting during fetal life ENVIRONMENTAL EFFECT (Hemminki, 2002: Danish migrating in Sweden) Comparison of testis cancer incidence between first and second generations The first generation immigrants retained the incidence as in their Country of origin, whereas the second generation (born in Sweden) Had a similar risk to native Swedes ENVIRONMENTAL EFFECT ?
  • Slide 6
  • Maternal risk factors Cook, Int J Epidemiol 38, 2009 GCT EPIDEMIOLOGIA
  • Slide 7
  • Peng, Plos One 4, 2009 Subfertility and GCTs risk RR Cryptorchidism RR: 2-10 fold GCT EPIDEMIOLOGIA
  • Slide 8
  • GENETIC FACTORS DIFFERENT INCIDENCE IN DIFFERENT ETHNIC GROUPS WHITE POPULATION (USA AND SOUTH ENGLAND) 5 fold HIGHER risk IN RESPECT TO BLACK POPULATION ?
  • Slide 9
  • BROTHER: 8 fold risk Sharing common: genetic factors intra uterine environmental factors FATHER: 4 fold risk Sharing common: -genetic factors FAMILIARITY for Testis cancer (Testicular Germ Cell Tumor,TGCT) is the STRONGEST RISK FACTOR
  • Slide 10
  • Copyright restrictions may apply. Crockford, G. P. et al. Hum. Mol. Genet. 2006 15 GENETIC FACTORS
  • Slide 11
  • Candidate gene approach: gene-environment interaction: -AR (CAG)n -ESR1 -P450 genes Germ cell development (mouse model) -DND1 -PDE11A Search for GENETIC FACTORS K. Krausz, Univ. Firenze
  • Slide 12
  • Chromosome 12 Chromosome analyses cDNA microarray analyses Rodriguez,Oncogene, 22, 2003 Chromosome number in the triploid range and shows specific chromosomal gains at chromosomne 7, 8, 12, 21 and X, and Losses at 11, 13, 18 80% TGCT
  • Slide 13
  • POTENTIAL GENETIC FACTORS INVOLVED IN TGCTs ESR1 AR P450 Modified from Chanock, Nat. Genet. 2009 12p 4q
  • Slide 14
  • The migratory pathway of primordial germ cells OCT4; AP PGCs Francavilla. J Submicr Cytol Path 1990
  • Slide 15
  • Rejpert-De-Meyts, Ann NY Acad Sci1120, 2007 Marcatori di PGCs Francavilla. J Submicr Cytol Path 1990
  • Slide 16
  • OCT-3/4 Seminoma Marcatori di PGCs AP-2Y CIS
  • Slide 17
  • Slide 18
  • WHO Horwich, Lancet, 367, 2006
  • Slide 19
  • Slide 20
  • J Urol, 180, 2008
  • Slide 21
  • Slide 22
  • Second Cancers in pts with testis cancer (S & NS) who survive > 10 yrs RR (95% CI) Connective Tissue 4.0 (2.3-6.3) Stomach 4.0 (3.2-4.8) Pancreas 3.6 (2.8-4.6) Mesothelioma 3.4 (1.7-5.9) Bladder 2.7 (2.2-3.1) Colon 2.0 (1.7-2.5) Esophagus 1.7 (1.0-2.6) Lung 1.5 (1.2-1.7) Tumor (solid) RR (95% CI) derived from Travis LB et Al, J Natl Cancer Inst 2005 ;97:1354
  • Slide 23
  • Rischio Neoplasia Seminoma Non Seminoma Rischio CVD
  • Slide 24
  • Risk for second Cancer &/or CVD Chirurgia Radio Ter Chemio
  • Slide 25
  • Urology, 67, 2006 SEMINOMI STADIO I : SORVEGLIANZA
  • Slide 26
  • SEMINOMI : STADI II CHT in caso di N multipli ed in prossimit del rene Krege S Europ Urol 2008 6 aa RFS Ricadute globali 0-15% Ricadute nel volume irradiato 0-2% OS > 99% II B 89% Classen JJ Clin Oncol 2003 II A 95%
  • Slide 27
  • Slide 28
  • 166 pazienti PAZIENTI IN AZOOSPERMIA DOPO CHEMIOTERAPIA 3 cicli PEB PAZIENTI IN AZOOSPERMIA DOPO RADIOTERAPIA dose totale 2600 cGy 3%6%12%34%37% 24 Mesi 12 Mesi 9 Mesi 6 Mesi 3 Mesi 6%9%19%26%4% 24 Mesi 12 Mesi 9 Mesi 6 Mesi 3 Mesi
  • Slide 29
  • CRIO3 MESI6 MESI24 MESI Tot/ejac.83.6 78.3 10.9 15.2 ***23.6 33.8 ***146.8 101.4 ** Mot.rett.31.6 16.9 11.8 12.8 **14.5 17.4 *41.4 14.0 ** Atipie66.8 13.3 85.2 13.8 ***84.4 16.4 ***62.7 7.7 ns PARAMETRI SEMINALI PRE E POST CHEMIOTERAPIA TUMORI TESTICOLARI Modificato da: Gandini et al. 2006
  • Slide 30
  • CRIO3 MESI6 MESI24 MESI Tot/ejac.115.9 110.1 30.0 51.9 **25.1 46.1 ***111.2 81.1 ns Mot.rett.33.2 16.0 17.8 16.3 ***15.9 19.2 **39.6 13.1 ns Atipie64.6 15.8 80.5 15.8 ***80.1 22.1 ***62.4 12.8 ns PARAMETRI SEMINALI PRE E POST Radioterapia TUMORI TESTICOLARI Modificato da: Gandini et al. 2006
  • Slide 31
  • LA RIPRESA DELLA SPERMATOGENESI DOPO TERAPIA NON E FUNZIONE DELLA QUALIT DEI PARAMETRI SEMINALI PRE-TERAPIA
  • Slide 32
  • Slide 33
  • Tumori Germinali Del Testicolo E il tumore maschile pi diffuso tra i 15 ed i 45 anni ENVIRONMENTAL EFFECT ? GENETIC FACTORS Origina da PGCs Elevata Sopravvivenza Rischio per Seconda Neoplasia & CVD Rischio per Infertilit Irreversibile
  • Slide 34
  • Csilla Krausz Universit di Firenze Loredana Gandini Universit di Roma La Sapienza

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