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35AF e 36AF Avaliacao Prognostica-copia 2
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Avaliao prognstica das
neoplasias
Prof. Ana FlixFaculdade de Cincias Mdicas30 de Novembro de 2015
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PROGNSTICO
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Prognstico
Diagnstico"
Tipo histolgico" Diferenciao
Estadiamento" Marcadores de prognstico
Consequncias do crescimentotumoral Leso e condio pre"malignas
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Prognstico
Diagnstico"
Tipo histolgico" Diferenciao
Estadiamento"
Marcadores de prognstico
Consequncias do crescimentotumoral Leso e condio pre"malignas
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TIPO HISTOLGICO
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Melanoma maligno
Leiomiosarcoma
Carc pavimento celular Carcinoma ductal
Linfoma no Hodgkin
GIST
Carc. neuroendcrino
Linfoma Hodgkin
Seminoma
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Tipohistolgicosegundo a
classificao daOMS
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Tipo histolgico
Categorias de prognstico#dependentes do tipo histolgico e estdio $
Bom #80$aos 5 anos % Intermdio Mau #
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Carcinoma do endomtrio &
tipos histolgico e o prognstico !"#$ !$&$' $' (')*&"$'
+,&$-()."/"&( !"#
%&'()'*+,-'*. !/#
0,1+(23*4(2( 56#
0(.$'$ 789:8#
123435' 635.5' :! 9 /"#
7,&"8(.(,6"5&$ (
9('&"8(.(,6"5&$6;#
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COMO SE IDENTIFICA O
TIPO HISTOLGICO?
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Tipo histolgico
Observao microscpica #cito ehistologia$em coloraes de rotina e em casosseleccionados dever ser complementada com:
imunohistoqumica"
Tumores pouco diferenciados"
Metstases reveladoras" Deteco de molculas com valor prognstico e
teraputico
diagnstico molecular"
Linfomas/leucemias; e Sarcomas; etc" Prognstico"
Doena mnima
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Caso clnicoHomem, 63 anos com
queixas de rouquidoh 1 ano recorre aomdico por dispneia eperda de peso de 10kgnos ltimos meses.Refere hbitos
tabgicos e alcolicosdesde sempre.No exame objectivo
mau estado geral
emagrecimentoacentuado
perda de massasmusculares
tumor com 4 cm nalaringe
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Imunohistoqumica Microscopia electrnica
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DIAGNSTICOCarcinoma pavimento celular, tipo sarcomatide
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MARCADORES IMUNO"
FENOTPICOS
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Melanoma maligno
Leiomiosarcoma
Carc pavimento celular Carcinoma ductal
Linfoma no Hodgkin
GIST
Carc. neuroendcrino
Linfoma Hodgkin
Seminoma
Cito-queratinas Cito-queratinas Cromogranina
Sinaptofisina
Vimentina
DesminaActina
CD45
CD20CD3
CD15
CD30CD20
pS100HMB45
CD117CD34
CD117PLAP
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MARCADORES EM
MICROSCOPIAELECTRNICA
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Melanoma maligno
Leiomiosarcoma
Carc pavimento celular Carcinoma ductal
Linfoma no Hodgkin
GIST
Carc. neuroendcrino
Linfoma Hodgkin
Seminoma
DesmossomasFil. intermdios
LumesDesmossomas
Fil. intermdios
Grnulosneuro-
endcrinos
Fil. finos
Fil. intermdios!
Melanossomas
!
!!
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MARCADORES
MOLECULARES
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Melanoma maligno
Leiomiosarcoma
Carc pavimento celular Carcinoma ductal
Linfoma no Hodgkin
GIST
Carc. neuroendcrino
Linfoma Hodgkin
Seminoma
! Status geneerBB2
!
! !
! cKit iso12
Marcadorescromossmicosclonalidade
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DO INFORMAO DE
ALVOS E DE RESPOSTA TERAPUTICA
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Melanoma maligno
Leiomiosarcoma
Carc pavimento celular Carcinoma ductal
Linfoma no Hodgkin
GIST
Carc. neuroendcrino
Linfoma Hodgkin
Seminoma
! Status geneerBB2
! !
BRAF, cKIT cKit, PDGF,Succinil
!
!
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:(;$34,$3$?"(' @(65-( 8(5'"@3(
A6$') 5,& $3( ?(,$-( D ?(,$-(
?
+,
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Journal of Pathology
J Pathol2010;220: 307315
Published online17 November 2009 in Wiley InterScience
(www.interscience.wiley.com)DOI:10.1002/path.2636
Invited Review
Does massively parallel DNA resequencing signify the endof histopathology as we know it?
Samuel AJR Aparicio1,2,3* and David G Huntsman2,3
1Molecular Oncology, BC Cancer Agency, 675 W10th Avenue, Vancouver V5Z 1L3, Canada2Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver V5Z 1L3, Canada3Department of Pathology, University of British Columbia, G227-2211 Wesbrook Mall, Vancouver, BC V6T 2B5 Canada
*Correspondence to:Samuel AJR Aparicio, MolecularOncology, BC Cancer Agency,675 W10th Avenue, VancouverV5Z 1L3, Canada.E-mail: [email protected]
No conflicts of interest weredeclared.
Received: 1 September 2009
Revised: 23 September 2009
Accepted: 26 September 2009
Abstract
Next-generation DNA sequencing devices have revolutionized cancer genomics by bringing
whole genome resequencing of patients tumours within practical and economic reach.
We present an overview of the techniques involved and review early results from the
resequencing of cancer genomes. The possible impacts of whole-genome and trancriptome
resequencing in clinical cancer research and the practice of pathology are discussed.
Copyright 2009 Pathological Society of Great Britain and Ireland. Published by John
Wiley & Sons, Ltd.Keywords: DNA sequencing; mutational heterogeneity; cancer genome; transcriptome;tissue sampling; mutational landscape; tumour evolution
"/
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"6
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Table 1
Some milestones in the clinical research of circulating cell-free DNA in the blood.
Year Event
1948 Discovery of cell-free DNA in blood
1965 Circulating DNA as a possible factor in oncogenesis
19661973 Detection of high levels in patients with systemic lupus erythematosus, rheumatoid arthritis, leukemia, and other diseases
1972/1975 Methodical aspects of determining in normal plasma samples1977 Detection of increased values in cancer patients depending on tumor stage and treatment
1989 Evidence of similar characteristics between circulating DNA and tumor DNA in cancer patients
19941999 Evidence of further tumor-related genetic alterations in circulating DNA
1997 Presence of fetal DNA in plasma of pregnant women
1998 Description of plasma DNA chimerism after transplantation
20002010 Circulating DNA in diagnosis and prognosis of numerous diseases (tumors, trauma, heart infarction, stroke etc.)
2010 Oncogenic transformation of cultured cells by circulating DNA in plasma
Biopsia lquida
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L:GMANIG0B
9"'
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AB0
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F+NRSG0I D 9+M7F7!7NF
Benign tumorAn abnormal proliferation ofcells driven by at least onemutation in an oncogene ortumor suppressor gene.These cells are not invasivewhich distinguishes themfrom malignant cells.
Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW.Cancer genome landscapes.Science. 2013 Mar 29;339(6127):1546-58.
Malignant tumor
An abnormal proliferation of cellsdriven by mutations in oncogenesor tumor suppressor genes thathas already invaded theirsurrounding stroma.
It is impossible to distinguish an isolated benign tumor cell from
an isolated malignant tumor cell. This distinction can be made
only through examination of tissue architecture.
"!
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DIFERENCIAO
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Graduao da diferenciao dasneoplasias malignas
Grau de semelhana com o tecido
normal Caractersticas das clulas
Pleomorfismo
Dimenses dos ncleos
Actividade mittica
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Diferenciao
normal
G1
G3
G2
Semelhana com onormal %morfo"
funcional
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Anaplasia
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Mitoses
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grau de diferenciao
definido pelo grau de semelhanado tumor com o tecido que lhe dorigem
pode ser subdividido em: "bem, mdio ou pouco diferenciado" Graus 1, 2 e 3 #eventualmente 4$
"
baixo grau e alto grau" ou, em casos especficos, tem um
sistema prprio
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exemplos
adenocarcinoma do clon e recto" Baixo e Alto grau
adenocarcinoma do endomtrio " Grau 1, 2 e 3
adenocarcinoma da prstata" Gleason
H critrios especficos para cada neoplasia
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Adenocarcinoma do endomtrio
Grau 1 a 5% e de 50% de
reas slidas
Avaliao da morfologia de ncleos por fazer up gradings
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score combinado de GleasonAdenocarcinoma da prstata
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score combinado de Gleason
3
Adenocarcinoma da prstata
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score combinado de Gleason
3
4
3+4=7
Adenocarcinoma da prstata
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3+4=7 4+3=7!
o predomnio de
reas de grau
histolgico 4 pode
retirar a indicao
operatria
Adenocarcinoma da prstata
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Prognstico
Diagnstico" Tipo histolgico"
Diferenciao
Estadiamento
Marcadores de prognstico
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ESTADIAMENTO
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Estadiamento
Avaliao clnica de pacientes com neoplasiaincide sobre a
Extenso local e disseminao tumoral
" Histria e exame fsico " Estudo analtico #bioqumico, hormonal,$"
Estudo imagiolgico " ESTUDO ANTOMO"PATOLGICO
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T Tumor
N Gnglios linfticos
M Metstases a distncia
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Crescimento invasivo do Adenocarcinoma
do clon
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Estadiamento
De acordo com os elementosT - Tumor
N - Gnglios linfticosM Metstases a distncia
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ADENOCARCINOMA DO
ENDOMTRIO
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Prognstico
Diagnstico" Tipo histolgico"
Diferenciao
Estadiamento
Marcadores de prognstico
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Marcadores de prognstico
Vrios tipos de elementos clnico emorfolgicos que so teis paraestimar grupos de doentes com umaevoluo clnica e que so utilizadosna seleco da teraputica
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OUTROS PARAMETROS
MORFOLGICOS DEPROGNSTICO
Carcinoma endometriide do endomtrio
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Factores de prognstico
com utilidadecomprovada
Tipo celular
Grau histolgico
Invaso vascularlinftica
Estdio da FIGO
p53 Ploidia tumoral
marcadores com utilidadeprovvel
Receptores deestrognios
Bcl2 Ki67 ErbB2
Densidademicrovascular
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Dados morfolgicos #que no entram noestadiamento na maioria dos tumores%
ex. Invaso linfo&vascular
Factor de prognstico independente da presena demetstases em gnglios linfticos
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Marcadores tumorais#ver tabela Robbins%
Protenas indicadoras da presena
de tumorescom possibilidade deserem usadas no diagnsticoe naorientao teraputica
SEROLGICOS
IMUNOHISTOQUMICOS
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IsoenzimasAntignios onco-fetais
Marcadores tumorais
" alfa"fetoprotena" antignio carcino"
embrionrio
" fosfatase cida prosttica" NSE
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Hormonas
Marcadores tumorais
" Tiroglobulina" Calcitonina" HCG " Catecolaminas
Mucinas
Ca 125
Ca 19-9
Ca 15-3
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Marcadores tumorais
Protenas especficas
" Imunoglobulinas" Antignio
especfico daprstata #PSA$
Figado
PSA
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Marcadores tumorais
Marcadores moleculares
"
Amplificao de genes
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Marcadores tumorais
ndice de proliferao Receptores hormonais Expresso de alvos
teraputicos Doena residual mnima
ERBB2 - CISH
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CARCINOMA DA MAMAexemplo
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Biomarcadores prognstico e de orientaoteraputica com utilidade comprovada
Tipo histolgico Grau histolgico Invaso vascular
linftica
Estdio ganglionar axilar a distncia
Receptores deestrognios eprogesterona
ERBB2
Utilidade em gruporestricto Ki"67
SEM utilidade comprovada em uso clnico h mais de 5anos mas onde so depositadas grandes esperanas Testes moleculares tipo Oncotype DX test ; MammaPrint test
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CARCINOMA DA MAMA
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com utilidade comprovada
Tipo histolgico Grau histolgico Invaso vascular
linftica Estdio
ganglionar axilar a distncia
Receptores deestrognios eprogesterona
ERBB2 Utilidade em grupo
restricto
Ki"67
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Outros
Oncotype DX test
Em casos seleccionados Custo aproximado 3000&
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RECIDIVA
Manifestao de novo de uma neoplasia maligna apstratamento e aps um perodo de tempo durante o qual aneoplasia no era detectvel
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PROGRESSONeoplasia maligna em disseminao ou agravamento local
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Tipos de recidiva
Local / Regional
No mesmo local Em gnglios
linfticos loco"
regionais
A distncia
Noutra localizao /rgo
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Como se avalia o risco de recidiva?
diferente em todos os doentes Depende de factores de prognstico
No possvel garantir a cura
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Sobrevivncia
Avalia"se habitualmente:" Taxa de sobrevivncia aos 5 anos" Taxa de sobrevivncia relativa
" Na comparao com a populao sem doena
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Caractersticas clnicas das neoplasias
efeitos dos tumores sobre o hospedeiro" Efeitos locais" Efeitos a distncia
Sndromes paraneoplsicas
Caquexia Metstases
causas de morte em doentes com neoplasia
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Efeitos das neoplasias benignas
Pela sua localizao N de tumores
Produo hormonal Alteraes gastro"intestinais Tamanho
Torso e enfarte
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Efeitos das neoplasias benignas
Pela sua localizao Adenomas pituitrio
comprimem a pituitria normale o quiasma ptico
Craniofaringiomas comprimem
e invadem o hipotlamo Mixoma auricular %bloqueia a
circulao intra"cardaca Meningiomas comprimem o
crebro Quistos colides bloqueiam o
fluxo do liquor
Adenomas pleomrficos
comprimem o nervo facial
MENINGIOMA
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Efeitos das neoplasias benignas
N de tumores Lipomas na "adiposis
dolorosa
Tumores neurais no
Sndrome de VonRecklinghausen's; Hamartomas na
esclerose tuberosa,etc.$
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Produo hormonal
Adenomas dapituitria, adrenais,
insulinomas,vipomas, reninomas,outros$
Alteraes gastro"intestinais
Hemorragia Obstruo
Intussuspeco Perda de potssio
Efeitos das neoplasias benignas
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Efeitos das neoplasias benignas
Tamanho cistadenomas
mucinosos do ovriocom 20 kg, etc.
Torso e enfarte tumores do ovrio
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Efeitos das neoplasias malignas
Invaso das estruturas normais e/ou
" Leso cerebral e herniao"
Edema pulmonar
"
Fracturas sseas" Trombocitopenia, granulocitopenia, anemia" Hemorragia #trombocitopenia e invaso vascular$"
Obstruo do ansas gastro"intestinais" Derrame peural
"
lceras e fstulas" Caquexia"
..
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Sndrome paraneoplsica
Podem ser a 1 manifestao de umaneoplasia
Podem provocar problemas clnicosgraves e letais Podem simular doena disseminada#metstases$e perturbar o raciocnio
para a teraputica
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Sndrome paraneoplsica
Sinais e sintomas no relacionadosdirectamente com a progresso localou a distncia da neoplasia
Sinais e sintomas no relacionadoscom secreo tumoral
ocorre em cerca de 10(
dosdoentes portadores de neoplasiamaligna
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Efeitos das neoplasias malignas
Sndromes paraneoplsicas" Febre" Sndrome de CUSHING" Virilizao " Feminizao" Hiponatrmia
"
Hipoglicmia
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Efeitos dos tumores malignos
" Sndrome carcinide #flushing, asma ediarreia$
" Policitmia"
Trombocitose " Anemia hemoltica auto"imune" Sndrome de hiperviscosidade " Neuropatia perifrica" Miastenia gravis
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Causas de morte por neoplasia
PNEUMONIA uma das causas mais frequentes de morteem pacientes com cancro. NEUTROPENIA #invaso da MO por clula sneoplsicas$ IMMUNOSUPPRESSO NO ESPECFICA OBSTRUO DAS VIAS EREAS #derrame pleural,
acamado$ ATELECTASIAS por dificuldade em tossir, acumulao de
secrees com colapso alveolar e infeco ASPIRAO de alimentos e de VMITO NARCTICOS suprimem o estmulo respiratrio
SPSIS#habitualmente bacilos gram#"$com choque #no facilmente identificvel uma origem da infeco %pulmo,bexiga, tumor necrosado$
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Causas de morte por neoplasia
HEMORRAGIA#crebro, intestino, outro local$ comum
em pacientes com trombocitopnia #invaso da MO$ TROMBOEMBOLISMO PULMONAR#acamados e
alguns pacientes ambulatrios$
FALNCIA RENAL #infiltrao tumoral, obstruoureteral$
SNDROMES PARANEOPLSICAS DOENA IATROGNICA espervel em doentes que
foram submetidos a cirurgia, radioterapia e quimioterapiamesmo se forem curados Ann. Int. Med. 111: 411, 1989
SUICDIO E a EUTANSIA
Menos comuns so: falncia de rgos como o fgado,tamponamento cardaco, etc.
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Sndrome da lse tumoral
A morte celular em massa pode levar morte dos doentes #tipos$" Hipercalimia
Paragem cardaca
" Hiperfosfatmia" Hiperuricmia
Insuficincia renal crnica
" Hipocalcmia
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REGRESSO
ESPONTNEA
1 em cada 140 000 casos #?$
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Regresso espontnea de tumores
Hemangioma em crianas" 2,6(dos recm nascidos" Incio s 2 a 4 semanas" Regresso ocorre pelos 10
anos#80"90($" Mecanismo
desconhecido
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Regresso tumoral
Carcinomas de clulas renais Neuroblastoma
Melanoma maligno Coriocarcinoma Hepatocarcinoma Carcinoma da bexiga
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Neuroblastoma
Sistema nervososimptico" Neuroblastoma" Ganglioneuroblastoma"
Ganglioneuroma
Mecanismos"
Diferenciao Hipometilao do ADN Diminuio da actividade da
telomerase
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Melanoma maligno
Primrio pode regredir" Estudo de 5000 melanomas malignos
2,2 casos em 1000 com regresso total do
primrio
Mecanismo" Imunolgico #CD4+$
World J. Surg. 19, 352-358, 19 95
WORLD
Journal of
SURGERY
9 995 by the Soci~t~
International e de Chirurgie
Spontaneous Regression of Human Melanoma/Nonmelanoma Skin Cancer:
Association with Infiltrating CD4 T Cells
Gary M. Halliday, Ph.D, Anita Patei, M.B., B.S., Michelle J. Hunt, M.B., B.S., M.Med.,
Frances J. Tefany, M.B., B.S., M.Med., Ross St.C. Barnetson, M.D.
Department o f Dermatology, University of Sydney, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales 2050,
Australia
Abstract. Spontaneous re gression occurs in some human malignant
melanomas a nd basal cell carcinomas (BCCs). We have compared the
cellular infiltra te in regressing and nonregressing tumors in order to
analyze the mechanism by which regression occurs. Regressing primary
melanomas and BCCs were infiltrated with a larger number of CD4*, but
no CD8 +, T lympho c~es t han were seen in nonregressing tumors. The
number of interleukin 2 receptor-positive (eariy activation marker) but
not transferrin receptor-posi tive ( intermediate ac tivation marker ~ T cells
was increased, indic ating that the infiltrating T cells were activated. Large
numbers of Langerhans cells, macrophages , and other class II major
histocompatibi lity complex (MHC)-expre ssing cell s were present but were
no increased in the regressing tumors. There were no detectable B
lymphoeytes, and the regressing tumor cells displaye d levels of HLA-DR
expressio n similar to those of the nonregressing tumors. Compari son of
sqnamous cell carcinoma (SCCs) with keratoacanthomas (KAs), which
are likely to be a spontaneously r egressing form of SCC, also showed
increased i nfiltration of activat ed CD&-, but not CD8 +, T cells within the
KA. A murine ultraviol et ((W)-induced squamous tumor that spontane-
ously regresses when transplanted into immunocompeten t syngeneic mice
was also infiltrated with incr eased numbers of activated CD&-, but not
CD8 +. T cells prior to and during rejection. These results i ndicate that
spontaneous regressi on of human skin tumors is likely to be immunolog-
ically mediated, and that CD4 + T lymphocytes seem to mediate this
regression.
There is Considerable experimental evidence that skin tumors can
induce effective immune responses in mice. Epithelial skin tumors
[1] and melanomas [2] are able to immunize syngeneic mice
against subsequent Challenge with the same tumor line. Addition-
ally, some ultraviolet UV) light-induced skin tumors in mice,
which grow progressively in immunosuppressed hosts, regress
when transplanted into syngeneic immunocompet ent mice. This
result implies that the immun e system is responsible for this tumor
regression [1, 3]. As transplantation experiments cannot be per-
formed in humans, evidence that the immune syst em plays a role
in controlling the growth of human tumors is less direct. The
antigen MAGE-1, which i capable of causing rejection of human
melanomas, has been clon ed [4]. This antigen, associated with
HLA-A1, is recognized by cytotoxic T lymphocytes, which are
capable of destroying MAGE-l-posit ive tumor cells [5]. Studies of
Correspondence to G. Halliday, Ph.D.
cellular infiltrates and other markers of immunologic activation,
as well as isolation of cytotoxic lymphocytes from patients,
suggests that the immune system at least limits growth of human
melanomas and n onmelanoma skin cancers [6, 7].
Analogous to the UV-induced regressor tumors in mice, a
number of human skin tumors regress spontaneously. Most
studies on the role of the immune system in controlling human
skin cancers have used progressively growing tumor material,
where tumor growth is outpacing tumor destruction. In contrast,
tumor cell death exceeds tumor growth in regressing human
tumors, providing valuable material for analysis of the biologic
process that can lead to tumor destruction. Lit tle is known about
spontaneously regressing human skin tumors. We have been
studying spontaneous regression of human primary malignant
melanoma [8], basal cell carcinomas BCCs) [9], and keratoacan-
thomas KAs) [10] over the past 5 years, and here we contrast and
review these findings.
It has been recognized for a number of years that some human
melanomas regress spontaneously. Spontaneously regressing hu-
man melanomas are infiltrated with large numbers of lymphocytic
cells [11], and cytotoxic T cell clones have been est ablished from
a regressing melanoma [12], suggesting that regression may be
immunologically mediated. The prognos tic significance of mela-
noma regression, however, remains obscure as metastasis still
occurs in these patients [13, 14]. Melanoma regression could often
escape detection and hence may be more common than is
reported. It is also likely that within a regressing lesion individual
tumor cells progress and change their tumor antigens so they
cannot be recognized by the ongoing immune response. These
cells may therefore survive regression and form metastases. BCCs
also spontaneously regress, although this subject has undergone
even less study than melanoma regression. BCCs are more
numerous in immunosuppressed patients [15], and regressing
BCCs are infiltrated with large numbers of inflammatory cells
[16], suggesting that the i mmune response may play a role in
regression of BCCs.
Keratoacantho ma is another example of a regressing human
skin tumor. KAs can be compared with squ amous cell carcinomas
SCCs), which generally run a progressive course that leads
Clnical data
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i l i l i
ill l i l i li l i l i illi
l li li i i l i il i l i
li i i i i li i li i i l i i l i l i
i i i l i i i ill l i i
i li i i I l li i l i l
li i l li i l i ili I i i i i li i l i ili
l l i i i l i i
li i l l i li i i l i l
Good et al. Genome Biology 2014, 15:438Organizing knowledge to enable personalization of medicine in cancer
Tissue
Increase value
AP report
Clinical decision
;!
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LESO E CONDIO PRE"
MALIGNA
Precursores clnicos
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provavelmente
todas as neoplasias desenvolvem"se apartir" condio e leso pr"maligna"
neoplasias benignas " outras
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leso pr&malignacondio pr&maligna
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condio pr&maligna
condio pr"maligna uma doenaque condiciona risco aumentado dedesenvolvimento de uma neoplasiamaligna
uma condio pr"maligna umantecedente ou um precursor temporal
de neoplasia maligna
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condio pr&maligna
no"hereditria" hiperplasia do endomtrio" colite ulcerosa
"
metaplasia pavimentosa do brnquio " metaplasia de Barrett" cirrose heptica" gastrite atrfica
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condio pr&maligna
hereditria" PAF "polipose adenomatosa familiar
#APC$" HNPCC "sndrome de Lynch" MEN "neoplasia endcrina mltipla
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condio pr&maligna
RISCO aumentado dedesenvolvimento de neoplasiamaligna
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leso pr&maligna
leso pr"maligna uma leso oualterao histolgica que antecede odesenvolvimento de uma neoplasiamaligna = DISPLASIA
a leso pr"maligna o antecedentelocal ou o precursor lesional de
malignidade
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condio =precursor temporal
leso = precursor lesional
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colite ulcerosa
Doena inflamatria crnicaintestinal
Processo inflamatrio recurrente, de etiopatogenia
desconhecida, limitado ao clon e recto commanifestaes extra&intestinais
Homem 44
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Homem, 44anos
Episdios dediarreia commuco esangue
Desconfortoabdominal
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Inflamao activa
Inflamao quiescente
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durao da doena" < 10 anos #
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leso pr&maligna
displasia
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displasia
termo impreciso mas PRTICO alteraes celulares muito irregulares que
ultrapassam a hiperplasia mas ainda no
so suficientes para serem chamadas deneoplasia
nos epitlios, h um grau de displasia quese mistura com o carcinomain situ
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CONDIO PR"MALIGNA
LESO PR"MALIGNA
NEOPLASIA INVASIVA
#METAPLASIA DE BARRETT$
#DISPLASIA EM METAPLASIA DE BARRETT$
#ADENOCARCINOMA$
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NEOPLASIAS BENIGNAS
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OUTRAS LESES
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outras
restos embrionrios" rim" maxilar
leses inflamatrias crnicas"lceras crnicas da pele " osteomielite e fistulizao
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