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8/19/2019 tumori bubrega

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MEDICINSKI FAKULTET UNIVERZITETA U BEOGRADU

INSTITUT ZA PATOLOGIJU

TEMA DIPLOMSKOG RADA:

TUMORI BUBREGA KOD ODRASLIH

Mentor: Doc. dr Sn! Rdo!e"#$ %&odr#$ St'dent: M#(#c V'&no"#$ )*+,-

Beo/rd0 !'n 1-)2.


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SADR3AJ

I UVOD4444444444444444444444444444.. .5

1.1 Anto6#! 7'7re/4444444444444444444444.5

1.2 U(o/ 7'7re/4444444444444444444444445

II TUMORI BUBREGA4444444444444444444444..8

1.) K(9##&c#! S"et9&e Zdr"9t"ene Or/n#;c#!e44444444444

1.1 Odre


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I UVOD

1.1 Anatomija bubrega

B'7re;# 9' rn# or/n# 96eten# ' retroer#tone(no6 ro9tor' n ;dn!e6 ;#d' 7do6en0 9o7e 9trne 6eno/ 9t'7 =' "#9#n# )1./r'dno/ # ).# 1.9(7#n9&o/ r(!en>. De9n# 7'7re/0 ot#9n't !etro60 o9t"(!en !e 6(o n#@e ' odno9' n (e"#. Te@#n 7'7re/ odr9(o/ o"e& !e o&o)*-/. Un'trn! 9trn 9dr@# 7'7re@n# #('9 &o!# "od# ' 7'7re@n' d'(!'0 &ro; &o!# ro(;e&r"n# # (#6n# 9'do"#0 ner"# # 'reter.

Sred !e o&r#"en r#!et(n#6 er#tone'6o60 9 9"# 9trn / o&r'@'!' 7'7re@n 9c#!069n &9'( # #7ro;n &9'(.

S9to!# 9e #; &orte&9 # 6ed'(e. O9no"n 6oro(o& # 'n&c#on(n !ed#n#c 7'7re/ !e neron.S" 7'7re/ 9e 99to!# od re&o 6#((#on neron. Neron 9e 99to!# od 7'7re@no/ te(c=&or'9&'(> # 7'7re@no/ t'7'(. Kor'9&'( 9e 99to!# od /(o6er'( =#n# / 9(et /'9to ;7#!en#&#(r &o!# o"e;'!' erentn' 9 eerentno6 rter#o(o6> # Bo'6no"e &9'(e =99to!# 9e #; r#!et(no/ # "#9cer(no/ (#9t>. B'7re@n# t'7'( #ne ro&9#6(n# t'7'(0 en(eo" et(! # d#9t(n#t'7'(. U(o/ t'7'( !e 9t"rn!e &onne 6o&r$e roce9#6 9orc#!e # 9e&rec#!e.

To&o6 9tren!0 7ro! 'n&c#on(n# neron 9e o9teeno 96n!'!e0 t&o d ' +-./od#n# 6no/#(!'d# #6!' 96o 5- od oetno/ 7ro!.

1. U!oga bubrega

O9no"n 'n&c#! !e or6#rn!e &onne 6o&r$e0 (# ored to/ 7'7re;# #6!' "#e9tr'&' '(o/'' odr@"n!' o6eo9t;e0 9to odr;'6e":

H re/'(c#!' r"note@e "ode # e(e&tro(#t0

H re/'(c#!' c#do 7;ne r"note@e0

H re/'(c#!' rter#!9&o/ r#t#9&0

H #;('#"n!e rod'&t 6et7o(#;6 # tetn# e6#&(#!0

H 9e&rec#!' or6on #td4

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). M(#/#!e" #r6#d 8. B'7re@n &r(#c )). Gorn!# o( )8. P#(e

1. Inter(o7'(rne rter#!e . Ureter )1. Inter(o7'(rn "en ). Bert#n#!e" &o(o6n

2. B'7re@n rter#! +. M( 7'7re@n #c )2. Neron

5. B'7re@n "en ?. F#7ro;n &9'( )5. B'7re@n d'(!*. #('9 )-. Don!# o( )*. Ve(#& 7'7re@n #c

II TUMORI BUBREGA

Ko # 9"e "r9te t'6or0 # t'6ore 7'7re/ 6o@e6o 'oteno ode(#t# n o9no"' n!#o"o/ 7#o(o&o/ onn! n 7en#/ne # 6(#/ne. M(#/n# t'6or# 9' d(e&o e$#0 ' o&"#r' o"e /r'en(;e 9e d"e od/r'e:

). Pr#6rn# t'6or# =t'6or# ore&( 7'7re@no/ ren#6>1. Se&'ndrn# t'6or# = 6et9t;e>.

N!'e9t(#!# t'6or# 7'7re/ odr9(# o9o7 9' &rc#no6# 7'7re@n# $e(#! =RCC ren( ce((crc#no6> # de(e 9e n 9(ede$e n!e$e #9to(o&e odt#o"e: 9"et(o$e(#!9 6'(t#(o&'(rn#c#9t#n#0 #(rn#0 ro6oo7n#0 6ed'(rn# # ne&(9##&o"n#. S"# RCC ot#' od t'7'(rn#e#t(n# $e(#! 7'7re/0 t!. neron.

Krc#no6 7'7re/ #n# 9"e/ 1 9"# &rc#no6 o"e&0 9 odr#(#&e )?-0--- no"# 9('!e"&o!# 9e d#!/no9t#&'!' 9"&e /od#ne. e$e 9e !"(! ' ;e6(!6 ' r;"o!'.

Ve$#n' 6(#/n# neo(;6# 7'7re/ #ne 9ord#n# 9('!e"#0 do& !e o&o 5 &rc#no6 7'7re@n# $e(#! n9(edno # o"e;no !e 9 ered#trn#6 &ncer9 9#ndro6#6. Do 9d 9'o#9n et#r# /("n t# n9(edn# &rc#no6 7'7re/: "on #e( L#nd'0 ered#trn# #(rn# &rc#no6 7'7re/ =PRC>0 B#rt o// D'7e =BD> # &rc#no6 7'7re@n# $e(#!

'dr'@en 9 ered#trno6 (e#!o6#o6to;o6 =LRCC>.

.1 K!a"i#i$a%ija S&et"$e '(ra&"t&ene Organi)a%ije* +i"to!o,$a$!a"i#i$a%ija tumora bubrega

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Tabela 2. TNM klasifikacija

T3M $!a"i#i$a%ija

T r#6rn# t'6or

T r#9'9t"o r#6rno/ t'6or n#!e 't"r


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Krc#no6 7'7re@n# $e(#! =RCC> red9t"(! /r'' 6(#/n#tet &o!# ot#' od e#te( 7'7re@n#&n(#$.

Epidemiološki podaci

RCC #n# re&o ?- 9"# t'6or 7'7re/ odr9(# &o!# 9e !"(!!' od!edn&o &od o7 o(. Nd"ne9to6 6e9t' !e &od 6'&rc0 9d6ne9to6 &od @en =)>. Inc#denc !"(!n! !e9r;6ern #nd'9tr#!9&o! r;"#!eno9t# ;e6(!e0 !e ' Jn' n e9to6 6e9t' ;!edno 9 nonHod/n (#6o6o60 do& !e ' 6n!e r;"#!en#6 ;e6(!6 n e9ne9to6 6e9t' ;!edno 9&rc#no6o6 n;or#n/9. Po!" &rc#no6 !e 6n! ' Ar#c# # A;#!#0 ; r;(#&' od J'@neA6er#&e0 tn#!e Ur'/"!0 /de !e )??*. /od#ne d#!/no9t#&o"n n!"e$# 7ro! no"# 9('!e" 'ce(o6 9"et'. Ze6(! 9 "#9o&o6 9too6 !"(!n! !e # e& Re'7(#&0 /de 9e n /od#n!e6n#"o' ot&r#!e )-H1- no"# 9('!e" n )--0--- 9tno"n#&0 9r;6erno &od o7 o( =1>.

Etiološki faktori

). P'en!e do&;n# # n!e$# &tor r#;#& ; n9tn& RCCH. Met n(#; 18 9t'd#! !e o&;( d 'en!e do"od# do ;n!no/ o"e$n! r#;#& od n9tn& o"e 7o(e9t#.T&od!e0 o&;no !e d re9tn& 'en! do"od# do 96n!en! r#;#& &od o7 o(.Pored 't#c! n n9tn& &rc#no60 red9t"(! # ne;"#9n &tor ; r;"o!';nredo"(o/ &rc#no6 7'7re/ =2>.

1. Go!;no9t or9t BMI =7od 699 #nde> !e o"e;n 9 n9tn&o6 &rc#no6 =5>.2. #erten;#! o"#en &r"n# r#t#9& !e &tor r#;#& ; n9tn& RCCH0 6d t'6or#

7'7re/ 6o/' d o9ee o!"' #erten;#!e. U r#(o/ o"o6e /o"ore 6no/e &oortne #9t'd#!e 9('! # &ontro(e. Kontro( #erten;#!e !e ' &ore(c#!# 9 96n!en!e6 r#;#& =*0 8>

5. A(&oo( 6d 't#c! (&oo( n o!"' &rc#no6 !o '"e& n#!e do"o(!no !9n0

odre


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Prognostički faktori kod karcinoma bubrežnih ćelija

Pro/no9t# &tor# 9' "eo6 &or#9n# ; odre


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9' (o7'(rne /r


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r#9'tn ' 9&oro * o"# t'6or # on /o"or# ' r#(o/ (o#!o! ro/no;#. Ve$# 7ro! 9"et(o$e(#!9RCCH 9dr@# $e(#!e #6'n9&o/ od/o"or0 t!. (#6oc#tn# #(# ne'tro#(n# #n#(trt.

S(#& 5. Krc#no6 ore&( 7'7re@n# $e(#!0 9"et(o$e(#!9 t#0 n'&(ern# /rd'9 ) =o F'r6'>

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S(#& *. Krc#no6 ore&( 7'7re@n# $e(#!0 9"et(o$e(#!9 t#0 n'&(ern# /rd'9 5 =o F'r6'>

Imunohistohemijski profil

Ve$#n o"# t'6or o;#t#"no re/'!e 9 ren( ce(( cr#c#no6 6r&ero6 =RCCHo6> CD)-0e#te(n#6 6e67rn9 6r&ero6 =EMA> # &r7on n#dr;o6 I =)-0 ))>. O7#no 9' o;#t#"n## n n#9&o6o(e&'(9&e c#to&ert#ne AE),AE20 CAM *.1 # &oe&9r#6#r!' "#6ent#n.

7.1b 0i"ti2ni mu!ti!o$u!arni $ar%inom bubre-ni+ e!ija

C#9t#n# 6'(t#(o&'(rn# &rc#no6 7'7re@n# $e(#! 9dr@# "e(# 7ro! c#9t# # 9et# &o!e 9e 99to!e od

6(# /r' 9"et(# $e(#! &o!e 9e ne 6o/' r;(#&o"t# od t'6or9 $e(#! t# 9"et(o$e(#!9&o/RCCH.

Makroskopski izgled

T'6or t##no &r&ter#e r#9'9t"o 7ro!n# 6(# # "e(# c#9t# &o!e 9' #9'n!ene 9ero;no6 #(#e6or/#no6 teno$'0 #7ro;no6 &9'(o6 od"o!ene od o9tt& 7'7re@no/ ren#6. U

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"#e od 1- 9('!e" "#

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I6'no#9toe6#!9 t'6or od/o"r 9"et(o$e(#!9&o6 RCCH'.

7.1% ;a4i!arni $ar%inom bubre-ni+ e!ija

P#(rn# RCC !e 6(#/n# t'6or 7'7re@no/ ren#6 9 #(rno6 #(# t'7'(o#(rno6/r


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Mikroskopski izgled

P#(rn# RCC !e &r&tr#9t#n o 6(#/n#6 e#te(n#6 $e(#!6 &o!e or6#r!' #(rne #(#t'7'(rne 9tr'&t're. e9to 9e 6o/' "#det# c#9te o7(o@ene t'6or9 $e(#!6 &o!e or6#r!' #(rne rod'@et&e &o!# ro6#n#r!' ' ('6en c#9te =)5>. T'6or 9dr@# r;"#!en'

#7ro"9&'(rn' 9tro6' # n&'#n' en'"# 6&ro/ # o(e9tero(9 &r#9t(. Ne&ro;e #e6or/#! 9' e9to r#9'tne &o # /rn'(e e6o9#der#n ' 6&ro/#6. e9to 9e 6o/' n$# #&(c##&o"n# &(&'('9# ' #(6.Po9to!e d" 6oro(o& t# PRCC =)5>:

H T#) t'6or# #6!' #(e re&r#"ene 9(o!e6 t'6or9 $e(#! 9 o9&'dno6 c#to(;6o6H T#1 t'6or#0 t!. n!#o"e $e(#!e0 9' "#e/ n'&(erno/ /rd'90 9 eo;#no#(no6 c#to(;6o6

# 9e'do9trt##&o"n#6 !edr#6.Sr&o6to#dn d#erenc#!c#! !e "#


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S(#& )-. Krc#no6 ore&( 7'7re@n# $e(#!0 #(rn# t#0 6oro(o t# 10n'&(ern# /rd'9 1 =o F'r6'>


Po9to!e 6#n#6(ne #6'no6oro(o&e r;(#&e #;6e


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S(#& )1. Krc#no6 ore&( 7'7re@n# $e(#!0 ro6oo7n# t#0 n'&(ern# /rd'9 1 =o F'r6'>


Sec##no ; d#!/no;' o"o/ t# t'6or !e d#';no c#to(;6t9&o 7o!en!e n (eo"o&o(o#dno /"o@.

7.1e Kar%inom Be!inije&i+ "abirni+ $ana!ia

Krc#no6 Be(#n#!e"# 97#rn# &n(#$ !e 6(#/n# e#te(n# t'6or &o!# n9t!e #; $e(#!Be(#n#!e"o/ 97#rno/ &n(0 &o!# ;!edno 9 'rote(o60 e67r#on(no ore&(o "od# od 'reter#no/ 'o(!&.


O"o !e red& t'6or0 &o!# #n# 6n!e od ) 9"# 7'7re@n# 6(#/n#tet. D'(o e$e 9e !"(! &od6'&rc ';r9t )2H+2 /od#n =1->.

Makroskopski izgled

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T'6or !e o7#no (o&(#;o"n ' centr(no6 de(' 7'7re@no/ ren#6. Ne!9no !e o/rn#en09#"o 7e(e 7o!e0 9 "e(##no6 &o! "r#r 10*H)1c6. Ne t'6or# r9t' t&o d #n"d#r!' 7'7re@n'&r(#c'0 9 6o/'$#6 o(!#6 ne&ro;e # 9te(#tn#6 nod'('9#6.

Mikroskopski izgled

D#!/no; o"o/ t'6or !e te&0 # 7;#r 9e n #9&(!'#"n!' o9t(# t'6or. K(9#n# &rc#no697#rno/ &n( #6 t'7'(rn# #(# t'7'(o#(rn# r9t0 @(e;de &o!e #n#(tr#' 7'7re@n# ren#6 #de;6o(9t#n' 9tro6' =1)>. Ne!9no !e o/rn#en od o&o(no/ t".

S(#& )2. Krc#no6 ore&( 7'7re@n# $e(#!0 Co((ect#n/ d'ct0n'&(ern# /rd'9 1 =o F'r6'>


I6'no#9toe6#!9&e &r&ter#9t#&e 9e re(#$' #;6e


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)).1.Trn9(o&c#!9 &rc#no6 &r&ter#e n#; ne&o(#&o r;(##t# trn9(o&c#! n ro6o;o6' )).10 &o!e re;'(t'!' ';#!o6 TFE2 /en 9 odre.

S(#& )5. Krc#no6 ore&( 7'7re@n# $e(#!0 Trn9(o&c#!9 &rc#no6=9"et(o$e(#!9 t#>


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N!9ec##n#! &r&ter#9t#& &rc#no6 !e o;#t#"no9t n TFE2 rote#n0 ored to/ o&;'!e o;#t#"no9t n CD)- # RCC0 AMACR0 re.

IV BE3IG3I TUMORI BUBREGA

7.1 Angiomio!i4om

An/#o6#o(#o6 !e 7en#/n# 6e;en#6(n# t'6or 9#n!en od 69no/ t"0 "reten9t# /(t6##cn# $e(#! # 7nor6(n# &r"n# 9'do" de7e(# ;#do".


3ene et#r# 't e$e o7o(e"!' od 6'&rc. S6tr 9e d !e t'7ero;n 9&(ero; =TS> rec##t#r!'$# &tor ; n9tn& t'6or =150 1*>. Kod o9o7 9 TS t'6or 9e d#!/no9t#&'!e &odo9o7 9tro9ne do7# 1* 2* /od#n0 do& 9e &od on# 7e; TS !"(! ' ';r9no! do7# 5* **/od#n =150 1*>.

Etiološki faktori

Ver'!e 9e d n/#o6#o(#o6 ';ro&'!e ro(#erc#!' er#"9&'(rn# e#te(n# $e(#! =18>.Me


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Makroskopski izgled

An/#o6#o(#o6 !e 9o(#trn# t'6or0 do7ro o/rn#en0 7e; &9'(e. Bo! t'6or "r#r # ;"#9# od r#9'9t" r;(##t# t". U&o(#&o 9' ' t'6or' r#9'tne 9"e tr# &o6onente0 6o@e od9e$t# n9"et(o$e(#!9 &rc#no6 7'7re@n# $e(#!0 '&o(#&o do6#n#r 96o 6##$n &o6onent0 od9e$

n (e!o6#o6. T'6or 6o@e 7#t# !&o "e(#.

Mikroskopski izgled

K(9#n# #9to(o tr#!9 #n# r#9'9t"o 69no/ t"0 /(t 6##$ # (oe or/n#;o"n# &r"n#9'do" de7e(# ;#do". Grn#c t'6or # ;dr"o/ t" !e otr. Neret&o 9e t'6or 6o@e r;"#t#9'7&9'(rno 9 redo6#nc#!o6 /(t 6##$n# $e(#!.

S(#& )*. An/#o6#o(#o6


An/#o6#o(#o6 !e o;#t#"n n 6e(noc#tne 6r&ere =MB5*0 MB*-0 CD820 t#ro;#n;0Mrt),Me(nA> # n /(t&o 6##$ne 6r&ere =/(t&o 6##$n# &t#n0 &(on#n0 6##$no 9ec##n#&t#n>

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7. ;a4i!arni a(enom bubrega

P#(rn# deno6# 9' t'6or# d#!6etr * 66 #(# 6n!e0 &o!e &r&ter#e #(rn #(# t'7'(rn/r. U9&(o' /enet9 #9#t#"n! &o! 9' r


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S(#& )8. P#(rn# deno6

7. On$o%itom

On&oc#to6 !e 7en#/n# e#te(n# t'6or 7'7re/ 99t"(!en od &r'n# $e(#! 7o/t#6#toondr#!6 # eo;#no#(no6 c#to(;6o6.


On&oc#to6 !e r"# o#9o Z#e( )?51. =2-> /od#ne0 &9n#!e K(e#n # V(en9# =2)>. #n# '&'no* 9"# 7'7re@n# neo(;6# e#t(no/ ore&( =21>. Bro!n #9#t#"n! 9' o&;( d 9e t'6or !"(! ' 9"#6 ';r9t#60 (# 9 #&o6 ' 9ed6o! decen#!# @#"ot. M'&rc# r#7(#@no d" 't e$eo7o(e"!' od @en. e$# 9' 9ord#n# 9('!e"#.

Klinička slika

Kod "e$#ne 7o(e9t rot#e 9#6to6t9 # 9('!no 9e ot&r#!e ' to&' rd#o(o&o/ re/(ed. Md0ne c#!ent# 9e !"(!!' 9 e6t'r#!o60 (7#(no6 69o6 ' 7do6en # 7o(o6 ' &'&o"#6.

Makroskopski izgled

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Z7e(e@eno !e ne&o(#&o 9('!e" ' &o!#6 7'7re;# 9dr@e "e(# 7ro! (e;#! on&oc#to6 9#ro 9e&tro6 6oro(o &r&ter#9t#&0 o't on&oc#to60 7en#/n# ro6en ' t'7'(#606#&roc#9t6 o&o t'6or9 $e(#! #td =22>4

NAPOMENA:

U o"o6 d#(o69&o6 rd'0 #9&(!'#"o ' 9"r' #('9trc#!e nto69&e /r.

V Literatura

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1. Fer( J0 Br F0 P#9n# P0 Prn DM=1--)>. GLOBOCAN 1---: Cncer Inc#dence0Mort(#t nd Pre"(ence Qor(d#de. IARC Pre99: Lon.

2. Prn DM0 Qe(n SL0 Fer( J0 Teo L0 To69 DB =1--2>. Cncer Inc#dence #n F#"eCont#nent9. IARC Sc#ent##c P'7(#ct#on9 No)**. IARC Pre99:Lon.

3. Prn DM0 P#9n# P0 Loe; AD0M9'er E =)??5>. At (e9t one #n 9e"en c9e9 o cncer #9 c'9ed 7 96on/.G(o7( e9t#6te9 or )?+*. Int J Cncer *?:5?5H*-5

4. IARC =1--1>. IARC nd7oo&9 o Cncer Pre"ent#on. Qe#/t contro( nd 9#c( ct#"#t. IARC Pre99: Lon

5. Co Q0 Gr#d(e G0 Fr'6en# JFJr0 Jr"o(6 B =1--->. O7e9#t0 erten9#on0nd ter#9& o dne cncer #n 6en. N En/( J Med 252: )2-*H)2))

6. Gro996n E0 Me99er(# F0 Bo&o V0 Go(d7o'rt U =1--1>. I9 tere n 99oc#t#on 7eteen erten9#on nd cncer 6ort(#t A6 J Med ))1: 5?H5+8.

7. L9 ME0 V'/r#n D =)?+>. Prneo(9t#c 9ndro6e9 #n ernero6. Se6#n Nero( : )12H)2-.

8. S'r#n G0 C9n S0 Go(#o A0 M'r GP =)?+?>. Prneo(9t#c nd 9ero(o/#c9ndro6e9 o ren( denocrc#no6. Se6#n Uro( : )*+H)).

9. Jco79 SC0 Ber/ SI0 L9on RK =)?+->. Sncrono'9 7#(ter( ren( ce(( crc#no6:tot( 9'r/#c( ec#9#on. Cncer 58: 125)H125*

10. McGre/or DK0 K'rn KK0 Co C0 T9o CC0 A( G0 Kr#9nn B0 Ro J0Lec/o J0 Tr'on/ LD =1--)>. D#/no9#n/ r#6r nd 6et9tt#c ren( ce(( crc#no6:te '9e o te 6onoc(on( nt#7od Ren( Ce(( Crc#no6 Mr&er. A6 J S'r/ Pto(1*: )5+*H)5?1.

11. P#t; S0 Mo(( R0 Stor&e( S0 Toene9 Q =)?+>. Ere99#on o #nter6ed#te #(6ent rote#n9 #n 9'7te9 o ren( ce(( crc#no69 nd #n ren( oncocto69. D#9t#nct#ono to c(99e9 o ren( ce(( t'6or9. L7 In"e9t *8: 851H8*2.

12. de( Vecc#o MT0 L;;# S0 Br'n# A0 Mn/#"cc# P0 Ce"en#n# G0 L';# P =)??+>.DNA (o#d ttern #n #((r ren( ce(( crc#no6. Corre(t#on #tc(#n#coto(o/#c( r6eter9 nd 9'r"#"(. Pto( Re9 Prct )?5: 21*H222.

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13. A6#n MB0 Cor(e99 CL0 Ren9 AA0 T#c&oo SK0 K'7'9 J0 Sc'(t; DS =)??>.P#((r =cro6o#(> ren( ce(( crc#no6: #9to6oro(o/#c crcter#9t#c9 nde"('t#on o con"ent#on( to(o/#c ro/no9t#c r6eter9 #n 81 c9e9. A6 J S'r/

Pto( 1): 81)H82*.

14. De('nt B0 E7(e JN =)??>. P#((r ren( ce(( crc#no6: c(#n#coto(o/#cnd #66'no#9toce6#c( 9t'd o )-* t'6or9. Mod Pto( )-: *2H*55.

15. Galatica Z, Kovatich A, Miettinen M (1995). Conitent e!"#eiono$ c%to&e#atin 7 in "a"illa#% #enal cell ca#cino'a. #ol *athol 3+ 205211.

16. Crott TB0 Frro GM0 L#e7er MM =)??*>. Cro6oo7e ce(( ren( crc#no6:c(#n#coto(o/#c( et're9 o *- c9e9. J Uro( )*5: ?85H?8.

17. Toene9 Q0 Stor&e( S0 R'6e(t J0 Mo(( R0 B'6 P0 Qerner S =)?++>.Cro6oo7e ce(( ren( crc#no6 nd #t9 "r#nt9 reort on 21 c9e9. J Pto( )**:1H1+.

18. Per(tHVent'r#n M0 Moc 0 A6#n M0 T67o(# P0 #(e6r#6 S0 M#t9c M0J"#dn J0 Str#c&er 0 Ro J0 A6#n MB =1--)>. Srco6to#d d#erent#t#on #n ren( ce((

crc#no6: 9t'd o )-) c9e9. A6 J S'r/ Pto( 1*: 1*H1+5.

19. Mrt#/non# G0 Pe M0 C#(o9# M0 Br'ne((# M0 Scr A0 Co(to C0 Trdn#co R0Z67on# G0 Bonett# F =1--)>. Pr"(7'6#n #9 con9tnt( ere99ed #n cro6oo7e ren(crc#no6. Mod Pto( )5: 8-H8.

20. Sr#/(e JR0 E7(e JN =)??+>. Co((ect#n/ d'ct crc#no6 o dne. Se6#n D#/nPto( )*: *5H8.

21. R'6e(t J0 Stor&e( S0 Mo(( R0 Scre T0 Toene9 Q =)??)>. Be((#n# d'ctcrc#no6: 'rter e"#dence or t#9 rre "r#nt o ren( ce(( crc#no6. #9toto(o/)+: ))*H)11.

22. Ar/n# P0 Antone9c' CR0 Co't'r#er J0 Fo'rnet JC0 Sc#ot R0 De7#ecHRcter M0'tc#n9on B0 Re'ter VE0 BocconHG#7od L0 T#66on9 CF0 e; N0 Ldn# M =1--1>.

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PRCCHTFE2 ren( crc#no69: 6oro(o/#c0 #66'no#9toce6#c(0 '(tr9tr'ct'r(0 nd6o(ec'(r n(9#9 o n ent#t 99oc#ted #t te t=W)> =)).1WX1)>. A6 J S'r/ Pto(18: )**2H)*88.

23.

Ar/n# P0 Antone9c' CR0 I((e# PB0 L'# M0 T#66on9 CF0 Ne7'r R0 Re'terVE0 Gr"#n AJ0 Pere;HAtde AR0 F(etcer JA0 Bec&#t JB0 Br#d/e JA0 Ldn# M=1--)>. Pr#6r ren( neo(969 #t te ASPLHTFE2 /ene '9#on o ("eo(r 9ot rt9rco6: d#9t#nct#"e t'6or ent#t re"#o'9( #nc('ded 6on/ ren( ce(( crc#no69 oc#(dren nd do(e9cent9. A6 J Pto( )*?: )?H)?1.

24. Kenne(( MJ0 Gro996n B0 Co KJ =)??5>. O'tco6e n(9#9 o 51 c9e9 oren( n/#o6o(#o6. J Uro( )*1: )?++H )??).

25. M'&# M0 Tor#&t C0 Ir# 0 T6# S0 S'/#'r 0 Tn& 0 S&6oto M0

#ro9# S =)??1>. Cr9t((o#d9 #n n/#o6o(#o6. ). A re"#o'9( 'nnot#ced eno6enon o ren( n/#o6o(#o6 occ'rr#n/ t #/ reX'enc. A6 J S'r/ Pto()8: )H)-

26. Bonett# F0 C#oder PL0 Pe M0 Mrt#/non# G0 Bo9# F0 Z67on# G0 Mr#';;# GM=)??2>. Trn97ronc#( 7#o9 #n (6n/#o6o6to9#9 o te ('n/. MB5* ord#/no9#9. A6 J S'r/ Pto( ): )-?1H))-1.

27. E7(e JN0 Qre( K =)??)>. Er( '6n ren( cort#c( e#te(#( neo(9#. Mod

Pto( 5: 5*A.

28. De('nt B0 E7(e JN =)??>. P#((r ren( ce(( crc#no6: c(#n#coto(o/#cnd #66'no#9toce6#c( 9t'd o )-* t'6or9. Mod Pto( )-: *2H*55 .

29. Ree9e AJM0 Q#n9tn(e DP =)?*+>. Te 96(( t'6orH(#&e (e9#on9 o te dne. Br J Cncer )1: *-H*)8.

30.

Z#e( L =)?51>. Z'r Kenntn#9 der Oncocto6e. V#rco9 Arc YA Pto( Ant2-+: 28-H2+1.

31. K(e#n MJ0 V(en9# [J =)?8>. Pro#6( t'7'(r deno69 o dne #t 9oHc((ed oncoct#c et're9. A c(#n#coto(o/#c 9t'd o )2 c9e9 o rre( reortedneo(96. Cncer 2+: ?-8H?)5.

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32. D"#9 CJJr0 Mo9to# FK0 Se9terenn IA0 o CK =)??)>. Ren( oncocto6.C(#n#coto(o/#c( 9t'd o )88 t#ent9. J Uro/en Pto( ): 5)H*1.

33. I9re(# RS0 Q#9e GJ0 Bn9( S0 Gerrd PS0 C9te(( A =)??*>. B#(ter( ren(

oncocto6to9#9 #n t#ent #t ren( #('re. Uro(o/ 58: +2H+*.

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