35
Immunocytochemistry
im m u n o sta in s
m id g u t
carcinoid tu m o rs
and foreg ut
and
h in d g u t neuroend ocrine tu m o rs to a lesser extent, w h ic h makes
it a m arker o f m id g u t orig in.
A n a lg o rith m ic approach to effusions w ith m etastatic carci-
n o m a is illustra ted in Fig. 3 5 .9 . Figures 3 5.1 0-3 5.14 illustra te
the u tility o f these m arkers in various m etastatic settings.
Breast Cytology
Therap ies fo r breast c arcinom a are changing ra p id ly in con-
cert w ith o u r increasing u n d e rsta n d in g o f th e m o le c u la r
e v o lu tio n o f th e disease. A lth o u g h th e diagnosis o f breast
c arcinom a b y lig h t m icroscop y is a re la tiv e ly s tra ig h tfo rw a rd
task fo r th e surgical p a th o lo g ist, th era p eu tic dem ands are
re s u ltin g in increasing dem ands o n th e p a th o lo g ist to cor-
rec tly diagnose th e specific types o f breast c arcinom a so th a t
a p p ro p ria te a n c illa ry p rog nostic and p red ictive tests w ill be
p e rfo rm e d fo r a p p ro p ria te therapy. T he b roa d categories o f
ductal and lo b u la r carcinom as o f th e breast represent the
m a jo rity o f breast carcinom as, b u t there are s trik in g d iffe r-
ences in m o rp h o lo g y, m o le c u la r a lte ra tio n s, and tre a tm e n t
strategies fo r each category. T h e d iag nostic d is c rim in a tio n o f
ductal versus lo b u la r neop lasm s is im p o rta n t in m a n y cir-
cum stances fo r th era p eu tic reasons. Indeed, th e diagnosis
o f breast c arcinom a in m etastatic sites rem a in s a sig n ific a n t
challenge, even today.
E-cadherin and p120 Catenin
T h e E-cadherin c om p lex is com posed o f th e tra nsm em b ran e E-
cadherin p ro te in and alpha, beta, gam m a, and p120 catenins,
w h ic h anc ho r th e E-cadherin p ro te in to th e cytop lasm ic actin
fila m e n ts. T he catenins are n o rm a lly located at th e ju n c tio n
o f th e cytoplasm and in te rn a l aspect o f th e cell m em brane,
w h ere th e y lin k w ith th e actin cytoskeleton. T h e y sho w a v a ri-
ety o f c e llu la r m o le c u la r a b n o rm a litie s th a t m ay re su lt in the
F ig . 3 5 .9 A lg o rith m ic a pp ro a ch fo r effusions w ith m e ta sta tic carcinom a.
CK, cyto ke ra tin; GCDFp, gross cystic disease flu id p ro te in ; TTF, th y ro id
tra n scrip tio n factor; W t, W ilm s' tu m o r.
absence o f E-cadherin, w h ic h is n o t detectable im m u n o h is to -
chem ically, characteristic o f lo b u la r neoplasm s. W e and others
have recently stud ied th e catenin m o le c u la r com p onents o f
th e E -c a d h e rin -c a te n in com p lex and have discovered a char-
acteristic cytop lasm ic re d is trib u tio n o f th e catenins in lo b u la r
neop lasia.70,71 In a d d itio n to th e loss o f im m u n o d e te c ta b le E-
cadherin in lo b u la r neoplasia, a m o st characteristic a b n o rm a l-
ity in lo b u la r neop lasia is th e d iffu se re lo c a liza tio n o f p120
catenin th ro u g h o u t th e cytoplasm , w h ic h yield s a d iffu se cyto-
p lasm ic p120 im m u n o s ta in in g pattern. In contrast, ductal n eo -
plasia retains th e m em b rane im m u n o s ta in in g p attern o f p120,
reflecting th e n o rm a l c o n stru c tio n o f th e E-cadherin com plex,
a lth o u g h ductal carcinom as m ay s h o w reduced m em b rane
im m u n o s ta in in g o f th e E -cadherin c om p lex com ponents. D if-
fuse signet rin g carcinom as o f stom ach and rectum m ay also
sho w p120 cytop lasm ic im m u n o s ta in in g , since th e y to o lack
E -cad herin.71 Figures 35.15 and 35.16 illu s tra te th e u tility o f
E -cadherin and p120 im m u n o s ta in s in th e p rim a ry as w e ll as
m etastatic setting in F N A b iop sy o f breast masses as w e ll as
a x illa ry ly m p h nodes.
Immunocytochemistry for Targeted Therapies
Im m u n oc ytoc he m istry is becom ing an im p o rta n t ad juvant fo r
targeted therapies such as ritu x im a b fo r C D 20-p ositive ly m p h o -
mas, cetuxim ab (E rb itux) fo r epiderm al g row th factor receptor
(EG FR )-positive head and neck and colon cancers, trastuzu-
m ab (H ercep tin) fo r H er2-p ositive breast cancers, and im a tin ib
(Gleevec) fo r g astrointestinal strom al tu m o rs (GISTs).
CD117
C -kit (C D 117) gene m u ta tio n s are characteristically seen in
GISTs and are dem onstrated b y IH C as increased p rotein expres-
sio n on surgical specimens. C -k it p rotein expression can be
exam ined in cytology specimens, b u t it is critical fo r 10% fo r-
m a lin to be the p rim a ry fixative. Few studies have successfully
p erform ed the IC C on cell b loc k m aterial, asp iration specimens,
and air-dried as w e ll as stained (R om anow sky-stained) slides
(Fig. 35.1 7 ). C -k it m u ta tio n a l analysis is also show n in th e same
study o n cell b loc k m ate ria l.72
HER2/neu
A p p roxim a te ly 1 5 -2 0 % o f invasive breast carcinom as express
H E R 2/neu, and th is is associated w ith p o or prognosis. Trastu-
zum ab, a hum an ize d m o n o c lo n a l a ntib od y directed against
the extracellular d o m a in o f H er2 p rotein, has been show n to
sig n ific an tly increase com plete pathologic response after ad ju-
van t chem otherapy. Therefore it is im p o rta n t fo r the lab o rato ry
to assess H ER 2 status o n b o th histo lo g ic as w e ll as cytologic
specimens fo r m anagem ent o f these patients. H E R 2 /n eu p rotein
expression b y IC C can be p erform ed on cell blocks, b u t p rim a ry
fo rm a lin fix a tio n is m and atory (Fig. 35.1 8 ).
C hrom og enic in s itu h yb rid iz a tio n (C IS H ) is a recent m ethod
w h ere in the H E R 2 /n eu gene copies are detected b y a silver reac-
tio n and visualized b y lig h t microscopy. A stud y th a t evaluated
the C ISH on ThinPrep-processed fine-needle aspirate specimens
fo u n d a good concordance between C ISH p erform ed o n liq u id -
based cytology specimens as com pared w ith paraffin-em bedded
tissue specimens.73,74
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