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Page 1: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Sandro Francavilla

Tumori Germinali Tumori Germinali

Del TesticoloDel Testicolo

EuropeanTraining Centre for Clinical Andrology

Università dell’Aquila

Focus on Endocrine Neoplasia, Roma, Luglio 2010

Page 2: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

McGlynn, J Clin Oncol 2005

GCTE’ il tumore maschile più diffuso nelle fascia di età tra i 15 ed i 45 anni

EPIDEMIOLOGIA

Page 3: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Rejpert-De-Meyts, Ann NY Acad Sci1120, 2007

GCT EPIDEMIOLOGIA

Page 4: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

TESTIS CANCER INCIDENCE RATE IN EUROPE

Differenze etnico-geografiche-fattori ambientali ?-fattori genetici ?

Page 5: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

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 theirCountry of origin, whereas the second generation (born in Sweden)Had a similar risk to native Swedes

ENVIRONMENTAL EFFECT

?

Page 6: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Maternal risk factors

Cook, Int J Epidemiol 38, 2009

GCT EPIDEMIOLOGIA

Page 7: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Peng, Plos One 4, 2009

Subfertility and GCTs risk

RR

Cryptorchidism RR: 2-10 fold

GCT EPIDEMIOLOGIA

Page 8: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

GENETIC FACTORS

DIFFERENT INCIDENCE IN DIFFERENT ETHNIC GROUPS

WHITE POPULATION (USA AND SOUTH ENGLAND) 5 fold HIGHER riskIN RESPECT TO BLACK POPULATION

?

Page 9: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

BROTHER: 8 fold risk

Sharing common:genetic factorsintra 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

Page 10: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Copyright restrictions may apply. Crockford, G. P. et al. Hum. Mol. Genet. 2006 15

GENETIC FACTORS

Page 11: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Candidate gene approach:Candidate gene approach:gene-environment interaction:-AR (CAG)n -ESR1-P450 genesGerm cell development (mouse model)-DND1-PDE11A

Search for GENETIC FACTORSSearch for GENETIC FACTORS

K. Krausz, Univ. Firenze

Page 12: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

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

Page 13: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

POTENTIAL GENETIC FACTORS INVOLVED IN TGCTsPOTENTIAL GENETIC FACTORS INVOLVED IN TGCTs

ESR1ARP450

Modified from Chanock, Nat. Genet. 2009

12p

4q

Page 14: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

The migratory pathway of primordial germ cells

OCT4; AP PGCs

Francavilla. J Submicr Cytol Path 1990

Page 15: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Rejpert-De-Meyts, Ann NY Acad Sci1120, 2007

Marcatori di PGCs

Francavilla. J Submicr Cytol Path 1990

Page 16: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

OCT-3/4

Seminoma

Marcatori di PGCs

AP-2Y

CIS

Page 17: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,
Page 18: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

WHO

Horwich, Lancet, 367, 2006

Page 19: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Horwich, Lancet, 367, 2006

Page 20: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

J Urol, 180, 2008

Page 21: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,
Page 22: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

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

Page 23: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Rischio Neoplasia

Seminoma

Non Seminoma

Rischio CVD

Page 24: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Risk for second Cancer &/orCVD

Chirurgia

Radio Ter

Chemio

Page 25: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Urology, 67, 2006

SEMINOMI STADIO I : SORVEGLIANZA

Page 26: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

SEMINOMI : STADI II

CHT in caso di N multipli ed in prossimità del rene Krege S Europ Urol 2008

6 aaRFS

Ricadute globali 0-15%Ricadute nel volume irradiato 0-2%OS > 99%II B 89% Classen JJ Clin Oncol 2003

II A 95%

Page 27: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,
Page 28: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

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

Page 29: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

CRIO 3 MESI 6 MESI 24 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

**

Atipie 66.8±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

Page 30: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

CRIO 3 MESI 6 MESI 24 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

Atipie 64.6±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

Page 31: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

LA RIPRESA DELLA SPERMATOGENESI

DOPO TERAPIA

NON E’ FUNZIONE

DELLA QUALITÀ DEI PARAMETRI SEMINALI

PRE-TERAPIA

Page 32: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,
Page 33: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Tumori Germinali Del TesticoloTumori Germinali Del Testicolo

E’ il tumore maschile più diffuso tra i 15 ed i 45 anni

ENVIRONMENTAL EFFECT

?GENETIC FACTORS

Origina da PGCs

Elevata Sopravvivenza

Rischio per Seconda Neoplasia & CVD

Rischio per Infertilità Irreversibile

Page 34: Sandro Francavilla Tumori Germinali Del Testicolo European Training Centre for Clinical Andrology Università dellAquila Focus on Endocrine Neoplasia, Roma,

Csilla Krausz Università di Firenze

Loredana Gandini Università di Roma “La Sapienza”


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