__  __    __   __  _____      _            _          _____ _          _ _ 
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Ant&iacute;geno Prost&aacute;tico Espec&iacute;fico
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<p style="text-align: justify;"><span class="content">Ant&iacute;geno
Prost&aacute;tico Espec&iacute;fico n&atilde;o &eacute;
uma prova sorol&oacute;gica muito precisa para c&acirc;ncer de
pr&oacute;stata, pois a sensibilidade e especificidade
n&atilde;o s&atilde;o muito boas, especialmente na faixa
intermedi&aacute;ria entre 4,1 a 10,0 ng/mL.<span id="more-231"></span></span></p>
<p style="text-align: justify;"><span class="content">1.
INTRODU&Ccedil;&Atilde;O</span></p>
<p style="text-align: justify;">O
desenvolvimento da an&aacute;lise automatizada de P.S.A. e o
resultado de rotina usando o soro do P.S.A. &eacute;
particularmente respons&aacute;vel para o recente aumento no
diagn&oacute;stico de c&acirc;ncer de pr&oacute;stata.</p>
<p style="text-align: justify;">Embora
ainda n&atilde;o tenha sido aprovado pelo F.D.A. para o
diagn&oacute;stico do c&acirc;ncer de pr&oacute;stata, o
P.S.A. est&aacute; sendo amplamente usado como uma modalidade de
diagn&oacute;stico e a Sociedade Americana de C&acirc;ncer e
Associa&ccedil;&atilde;o Urol&oacute;gica Americana
t&ecirc;m recomendado o uso anual da
determina&ccedil;&atilde;o de rotina do P.S.A.</p>
<p style="text-align: justify;">O
P.S.A. &eacute; usado n&atilde;o somente para o
diagn&oacute;stico de homens assintom&aacute;ticos para
c&acirc;ncer de pr&oacute;stata, mas tamb&eacute;m para
monitorar os resultados de cirurgias essenciais, terapia de
radia&ccedil;&atilde;o, de priva&ccedil;&atilde;o de
andr&oacute;genos e tratamento do c&acirc;ncer
refrat&aacute;rio de pr&oacute;stata.</p>
<p style="text-align: justify;">Diante
deste cen&aacute;rio cl&iacute;nico, a efic&aacute;cia da
terapia pode ser exatamente monitorada pela mudan&ccedil;a na
superf&iacute;cie do soro do P.S.A., advindo de valor
pr&eacute;-terap&ecirc;utico. Em adi&ccedil;&atilde;o,
o P.S.A. tem mostrado valor progn&oacute;stico precedendo o
resultado de cirurgia essencial e terapia de
radia&ccedil;&atilde;o.</p>
<p style="text-align: justify;">Apesar
da sua utilidade, o uso do P.S.A. permanece controverso. Em todas as
aplica&ccedil;&otilde;es, incluindo a sua
signific&acirc;ncia depois de cirurgia essencial, onde sua
for&ccedil;a sup&otilde;e-se seria de maneira nenhuma
controversa, h&aacute; discord&acirc;ncias em como o P.S.A.
poderia ser usado e interpretado. O uso e a
interpreta&ccedil;&atilde;o do soro P.S.A. permanece
controverso porque o P.S.A. n&atilde;o &eacute; um marcador de
c&eacute;lulas cancerosas da pr&oacute;stata, e sim um marcador
de c&eacute;lulas epiteliais da pr&oacute;stata. Portanto,
carece de especificidade.</p>
<p style="text-align: justify;">O
P.S.A. pode estar aumentado no soro devido a algum estado
patol&oacute;gico que induzir&aacute; a sa&iacute;da do
P.S.A. at&eacute; o soro. Esses estados incluem prostatites
cr&ocirc;nica e aguda, comumente associadas com hiperplasia
prost&aacute;tica benigna (HPB), obstru&ccedil;&atilde;o
ductal comumente vista em HPB e em algumas
manipula&ccedil;&otilde;es cir&uacute;rgicas da
pr&oacute;stata, incluindo bi&oacute;psia,
ressec&ccedil;&atilde;o e examina&ccedil;&atilde;o
vigorosa. O P.S.A. no soro pode estar diminu&iacute;do por algum
fen&ocirc;meno que inibe a fun&ccedil;&atilde;o celular
normal.</p>
<p style="text-align: justify;">A
produ&ccedil;&atilde;o do P.S.A. est&aacute; sob controle
andr&oacute;geno (testosterona, dihidrotestosterona, receptores de
andr&oacute;geno) e, alguma perturba&ccedil;&atilde;o de
seu mecanismo regulat&oacute;rio, pode escurecer a
superf&iacute;cie do soro de P.S.A.</p>
<p style="text-align: justify;">Alguns
fatores s&atilde;o capazes de afetar a
regula&ccedil;&atilde;o andr&oacute;gena, incluindo
absor&ccedil;&atilde;o de estr&oacute;genos, terapia
farmacol&oacute;gica (inibidores da 5-a-redutase, inibidores
competitivos de receptores de andr&oacute;genos e inibidores de
horm&ocirc;nio luteinizante) e disfun&ccedil;&atilde;o
testicular de envelhecimento. Em adi&ccedil;&atilde;o,
transforma&ccedil;&atilde;o maligna pode diminuir a
produ&ccedil;&atilde;o de P.S.A. Como c&eacute;lulas
diferenciadas, suas habilidades para produzir prote&iacute;nas
respons&aacute;veis por fun&ccedil;&otilde;es normais das
c&eacute;lulas podem diminuir. Esta
observa&ccedil;&atilde;o &eacute; verdadeira para
c&acirc;ncer de pr&oacute;stata, a qual pode demonstrar somente
fraca colora&ccedil;&atilde;o imunohistoqu&iacute;mica
positiva para P.S.A.</p>
<p style="text-align: justify;">Por
estas raz&otilde;es, o soro do P.S.A. &eacute; um imperfeito
marcador de tumor e, ainda assim, &eacute; provavelmente o melhor
marcador de tumor que conhecemos. Uma das maiores
limita&ccedil;&otilde;es da interpreta&ccedil;&atilde;o
do P.S.A. ocorre secundariamente para a
contribui&ccedil;&atilde;o vari&aacute;vel da hiperplasia
prost&aacute;tica benigna para a superf&iacute;cie do soro. Em
geral, c&acirc;ncer &eacute; incomum &agrave;
regi&atilde;o normal do soro (i.e. &pound; 40 ng/mL) e comum a
regi&otilde;es abaixo de 10,0 ng/mL. &Eacute; entre 4,1 e 10,0
ng/mL que hiperplasia prost&aacute;tica benigna e c&acirc;ncer
de pr&oacute;stata coexistem, mas com uma incid&ecirc;ncia de
aproximadamente 80-85% e 15-20%, respectivamente.</p>
<p style="text-align: justify;">A
aplica&ccedil;&atilde;o final do P.S.A. &eacute; em
determinar que epit&eacute;lio na pr&oacute;stata
n&atilde;o &eacute; de tipo prost&aacute;tico. Isto se tem
demonstrado recentemente ser de grande utilidade pr&aacute;tica em
confirmar o diagn&oacute;stico de duas
prolifera&ccedil;&otilde;es n&atilde;o
neopl&aacute;sicas que poderia envolver pr&oacute;stata e ser
confundida com adenocarcinoma prost&aacute;tico, especificamente
adenoma nefrog&ecirc;nico da uretra e hiperplasia
meson&eacute;frica.</p>
<p style="text-align: justify;">Embora
estes diagn&oacute;sticos sejam inicialmente suspeitados na
examina&ccedil;&atilde;o do esfrega&ccedil;o da
hematoxilina-eosina, &eacute; proveitoso na base
confirmat&oacute;ria do desempenho da
colora&ccedil;&atilde;o para P.S.A., porque quando negativos,
eles suportam o diagn&oacute;stico do adenoma
nefrog&ecirc;nico. De maneira similar, foi recentemente documentado
que hiperplasia meson&eacute;frica envolveria a pr&oacute;stata
e poderia levar a erro no diagn&oacute;stico de adenocarcinoma
prost&aacute;tico. Embora, novamente o diagn&oacute;stico
&eacute; suspeitado na base de rotineiros esfrega&ccedil;os
coloridos, colora&ccedil;&otilde;es negativas do
epit&eacute;lio linear dos t&uacute;bulos
meson&eacute;fricos para P.S.A. jogam uma parte na
confirma&ccedil;&atilde;o do diagn&oacute;stico.</p>
<p style="text-align: justify;">2.
DIAGN&Oacute;STICO LABORATORIAL</p>
<p style="text-align: justify;">2.1.
M&eacute;todo 1 &ndash; Pesquisa Imunol&oacute;gica do
P.S.A. no Soro:</p>
<p style="text-align: justify;">O
P.S.A. &eacute; uma prote&iacute;na com atividade
enzim&aacute;tica e &eacute; encontrado no soro de duas formas:
na forma livre e complexado com anti-proteases.</p>
<p style="text-align: justify;">Quando
elevadas concentra&ccedil;&otilde;es de P.S.A. s&atilde;o
encontradas no soro, h&aacute; possibilidade de hipertrofia
prost&aacute;tica e/ou c&acirc;ncer de pr&oacute;stata. No
soro, a atividade proteol&iacute;tica do P.S.A. &eacute;
inibida pela a-1-quimiotripsina, a-2-macroglobulina e outras
prote&iacute;nas de fase aguda.</p>
<p style="text-align: justify;">&Eacute;
secretado pelas c&eacute;lulas epiteliais das gl&acirc;ndulas
hep&aacute;ticas. A a-1-quimiotripsina &eacute; a maior forma
de complexa&ccedil;&atilde;o do P.S.A., cuja forma livre
&eacute; a menor fra&ccedil;&atilde;o no soro.</p>
<p style="text-align: justify;">A
padroniza&ccedil;&atilde;o dos
imunoensaios do P.S.A. &eacute; necess&aacute;ria. Os
benef&iacute;cios
dessa padroniza&ccedil;&atilde;o s&atilde;o os seguintes:</p>
<p style="text-align: justify;">-
os resultados ser&atilde;o uniformes
e permitir&atilde;o que pacientes sejam
&ldquo;testados&rdquo; por
diferentes ensaios e laborat&oacute;rios.</p>
<p style="text-align: justify;">-
pesquisa significativa em c&acirc;ncer de pr&oacute;stata pode
ser utillizada por permitir a compara&ccedil;&atilde;o de dados
cl&iacute;nicos e estudos cl&iacute;nicos com o uso de
diferentres ensaios de P.S.A.</p>
<p style="text-align: justify;">Muitos
fatores contribuem para os problemas de
padroniza&ccedil;&atilde;o, dentre os quais est&atilde;o os
seguintes:</p>
<p style="text-align: justify;">-
P.S.A. isoformas usadas para produzir anticorpos anti-P.S.A.</p>
<p style="text-align: justify;">-
reatividade espec&iacute;fica dos anticorpos. Os anti-P.S.A. podem
possuir diferentes reatividades e afinidades pelas v&aacute;rias
formas de P.S.A. livre ou complexadas.</p>
<p style="text-align: justify;">Resultado:</p>
<p style="text-align: justify;">A
concentra&ccedil;&atilde;o de P.S.A. &eacute; diretamente
proporcional &agrave; do anticorpo anti-P.S.A. usado.</p>
<p style="text-align: justify;">C&acirc;ncer
de pr&oacute;stata &eacute; incomum &agrave;
regi&atilde;o normal do soro, ou seja, &pound; 40 ng/mL.</p>
<p style="text-align: justify;">Valores
entre 4,1 e 10,0 ng/mL,
coexistem hiperplasia prost&aacute;tica benigna (80 &ndash;
85%) e
c&acirc;ncer de pr&oacute;stata (15 &ndash; 20%).</p>
<p style="text-align: justify;">2.2.
M&eacute;todo 2 &ndash; Forma&ccedil;&atilde;o de
Manchados Imunohistoqu&iacute;micos para P.S.A.:</p>
<p style="text-align: justify;">T&eacute;cnica:</p>
<p style="text-align: justify;">Peda&ccedil;os
de epit&eacute;lio de pr&oacute;stata colocados em uma
l&acirc;mina, formam manchados em presen&ccedil;a de anticorpos
anti-P.S.A., devido a rea&ccedil;&atilde;o deste com o P.S.A.,
coloridos por hematoxilina-eosina.</p>
<p style="text-align: justify;">Resultado:</p>
<p style="text-align: justify;">Quando
h&aacute; forma&ccedil;&atilde;o de manchados coloridos no
epit&eacute;lio, a rea&ccedil;&atilde;o indica que as
c&eacute;lulas retiradas da pr&oacute;stata s&atilde;o da
pr&oacute;stata, levantando a hip&oacute;tese de
diagn&oacute;stico de c&acirc;ncer prost&aacute;tico,
descartando hip&oacute;teses de neoplasias que envolvem a
pr&oacute;stata, adenoma nefrog&ecirc;nico da uretra e
hiperplasia meson&eacute;frica.</p>
<p style="text-align: justify;">Essa
t&eacute;cnica serve, portanto,
para diferenciar c&acirc;ncer de pr&oacute;stata dessas outras
neoplasias envolvendo a pr&oacute;stata.</p>
<p style="text-align: justify; font-weight: bold;">Observa&ccedil;&atilde;o:</p>
<p style="text-align: justify;">Esse
m&eacute;todo n&atilde;o &eacute;
espec&iacute;fico, para diagn&oacute;stico de c&acirc;ncer
de
pr&oacute;stata, uma vez que P.S.A. &eacute; marcador do
epit&eacute;lio de pr&oacute;stata e n&atilde;o da
gl&acirc;ndula em
si. Al&eacute;m disso, quando se trata de c&acirc;ncer de
pr&oacute;stata, a rea&ccedil;&atilde;o &eacute; fraca,
devido a
altera&ccedil;&otilde;es de s&iacute;ntese de
prote&iacute;nas pelas
c&eacute;lulas malignas, podendo haver um falso-negativo.</p>
<p style="text-align: justify;"><strong>Valores
de refer&ecirc;ncia</strong></p>
<p style="text-align: justify;">Os
resultados do teste de PSA referem o n&iacute;vel de PSA detectado
no sangue. Os resultados s&atilde;o referidos em nanograma por
mililitro (ng/ml) no sangue. As refer&ecirc;ncias s&atilde;o as
seguintes:</p>
<ul style="text-align: justify;">
  <li>0 a 2,5 ng/ml &eacute;
considerado um valor baixo</li>
  <li>2.6 a 9,9 ng/ml &eacute;
considerado um valor ligeiro a moderado</li>
  <li>10 a 19,9 ng/ml &eacute;
considerado um valor moderadamente elevado</li>
  <li>20 ng/ml ou mais
&eacute; considerado um valor significativamente elevado</li>
</ul>
<p style="text-align: justify;">N&atilde;o
h&aacute; um valor espec&iacute;fico para se dizer que um
n&iacute;vel de PSA &eacute; normal ou anormal. Contudo, quanto
maior o n&iacute;vel de PSA, maior &eacute; a probabilidade de
cancro estar presente. V&aacute;rios factores podem causar a
flutua&ccedil;&atilde;o de n&iacute;veis de PSA. Quando os
n&iacute;veis de PSA sobem com o tempo, outros testes
poder&atilde;o ser necess&aacute;rios.</p>
<p style="text-align: justify;">REFER&Ecirc;NCIAS
BIBLIOGR&Aacute;FICAS</p>
<p style="text-align: justify;">1.
COHIN, R. et al. <span style="font-weight: bold;">Diagnostic
imunopathology</span>.
2.ed. New York: Rawen Press,&nbsp;1994. 2600 p.</p>
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