35
Immunocytochemistry
b u t n o t lu n g adenocarcinom a. C love r and associates fo u n d rare,
w eak s ta in in g fo r c yto ke ra tin -5 /6 in 4 o f 27 lu n g adenocarci-
nom as w ith th e D 5 /1 6 B 4 a n tib o d y clone,43 whereas O rd onez
fo u n d focal s ta in in g in 6.5% o f n o n p u lm o n a ry adenocarci-
nom as and d iffuse cytop lasm ic s ta in in g in a ll m esotheliom as
and squam ous cell carcinom as.44 T he s e n s itiv ity and specifi-
c ity o f th is sta in to d istin g u ish m a lig n a n t m e s o th e lio m a fro m
ad enocarcinom a in p leu ral e ffusions is 9 0 -1 0 0 % .45 However,
th is m a rke r is o f n o value to d iffe re n tia te m a lig n a n t m esothe-
lio m a fro m m etastatic p u lm o n a ry squam ous cell carcinom a.
It is im p o rta n t to keep in m in d th a t certain breast m alignancies
express c yto ke ra tin -5 /6 as w e ll. G iven these data, cytokera tin-
5 /6 is useful to id e n tify e p ith e lio id m a lig n a n t m e so th e lio m a
and
reactive
m e so th e lia l
cells
fro m
adenocarcinom a.
A h is to ry o f th e p rim a ry carcinom a helps in in te rp re ta tio n o f
th is stain.
Wilms' Tumor Gene Product
W ilm s ' tu m o r gene (W T 1) is a tu m o r suppressor gene present
o n chrom osom e 11. It was first reported as a candidate fo r m a in
gene im p lic a tio n in the developm ent o f W ilm s ' tu m o r. The
im m u n o h isto c h e m ic a l expression o f W T1 was dem onstrated
in various neoplasm s. A m a jo rity o f e p ith e lio id m esotheliom as
and a sm all percentage o f sarcom atoid m esotheliom as express
W T1. Strong im m u n o re a c tivity fo r W T1 is dem onstrated in
desm oplastic sm all ro u n d cell tu m o rs.45 W T1 represents an
effective m arker fo r m esotheliom as in cell b loc k preparations
and can aid in its d istin c tio n fro m p u lm o n a ry adenocarcinom a.
C a u tio n sho uld be exercised w h en th e m etastatic carcinom a is
o f ovarian o rig in, since a strong nuclear p o s itiv ity is also seen in
reactive m esothelial cells.
D2-40
D 2 -40 was in itia lly reported to be a m arker fo r lym p h atic
e n d o th e liu m b u t was fo u n d to be expressed b y benign as w e ll as
neoplastic m esothelial cells. D 2-40, lik e W T 1, is em erging as a
sensitive m arker b u t lacks specificity due to reported expression
in certain adenocarcinom as.46,47
GLUT-1
Recently, G LU T-1, a m em b er o f th e fa m ily o f glucose tra n -
sp orter (G LU T) iso fo rm s, w h ic h fa c ilita te th e e n try o f g lu -
cose in to cells, has been fo u n d to be expressed in a va rie ty
o f m alignancies. Im m u n o h is to c h e m ic a l G LUT-1 expression
d em onstrated b y lin e a r plasm a m em b rane sta in in g , som e-
tim e s w ith cytop lasm ic sta in in g , is a sensitive and specific
im m u n o h is to c h e m ic a l m a rke r e nab ling d iffe re n tia l diagnosis
o f reactive m e so th e lia l cells fro m m a lig n a n t m e so th e lio m a ,
b u t it c an no t d isc rim in a te m a lig n a n t m e s o th e lio m a fro m lu n g
carcinom a.48,49
Non Mesothelial (Adenocarcinoma) Markers
T he highest se n sitivity fo r adenocarcinom as can be achieved
w ith the staining c o m b in a tio n o f negative m esothelial m arkers
and p o s itiv ity fo r any adenocarcinom a m arkers (BG-8, M O C -31,
Ber-EP4, CEA, o r B72.3).
MOC-31
M O C-31 is a m on oc lo na l antib od y th a t has recently become
com m ercially available th a t recognizes an epithelial-associated,
transm em brane glycop rotein o f 40 kDa. Squam ous cell carci-
nom as, adenocarcinom as, and sm all-cell carcinom as show a
m em brane-staining pattern. The u tility o f th is m arker to d istin -
guish adenocarcinom a fro m m esothelial cells has been reported
b y few studies.49-52 The sen sitivity and specificity o f this m arker in
these studies has been reported to be between 78 and 100%. In the
literature, the rep orting o f M O C-31 expression in m esotheliom as
is contradictory, ranging fro m 0 to 88% ; however, the n um b er o f
cases in these studies were sm all. In a recent study b y Y aziji et al.,
M O C-31 was id en tifie d am ong five n o n m e soth elial m arkers in
a d d itio n to BG-8 to d isting uish e p ith e lio id m esothe liom a fro m
adenocarcinom a.40 The expression in reactive m esothelial cells
is less than 2% as reported by various studies. M O C-31 repre-
sented an effective m arker fo r m etastatic carcinom a in cell b lock
preparations and also aids in d isting uishing between benign and
m alig n an t m esothelial cells in these tum ors.
BG-8
The role o f A B H b lo o d antigens in tu m o r metastasis and in solid
tu m o rs has been addressed, w ith the Lewis Y antigen precursor
postulated as playing a ro le in tu m o r spread. BG-8, an antib od y
against Lewis antigen, has been show n in tissue specimens as
w e ll as cell b loc k specimens to have a sen sitivity and specificity
o f 86% and 90% in d iffe re n tia ting adenocarcinom a fro m epi-
th e lio id m esothe liom a .36 A recent study b y Y a ziji et al. evaluat-
ing 12 antibod ies fo r d isting uishing e p ith e lio id m esothe liom a
fro m adenocarcinom a id en tifie d BG-8 and M O C-31 due to th e ir
h ig h specificity, m aking th em o p tim a l m arkers to p ositively
id e n tify adenocarcinom a.40 BG-8 shows a cytoplasm ic staining
pattern o f the adenocarcinom a cells; however, caution is needed
w ith th is stain, as a sm all percentage o f isolated m esothelial
cells can show a nonspecific p ositive reaction.36
Ber-EP4
Ber-EP4 was first introd uced b y Latzka and coworkers as a m o n o -
clonal a ntib od y th a t reacts w ith tw o glycoproteins th a t are on
the surface as w e ll as in the cytoplasm o f e p ith elial cells and
do n o t react w ith m esothelial cells to a sig nificant degree. The
ro le o f Ber-EP4 in e p ith elial m alignancies has been reported in
the lite rature b y several studies, w ith a sen sitivity and specificity
up to 100%. It has the advantage o f h ig h sen sitivity and ease
o f in te rp re ta tio n because o f the h ig h percentage o f tu m o r cells
stained, characteristic m em branous staining, and lack o f cross-
reaction w ith background in fla m m a to ry cells. C a u tio n m ust be
exercised, because isolated m esothelial cells m ay stain.53-55
Monoclonal CEA
C arcinoem b ryonic antigen is a 180-kD a glycop rotein th a t is
50% carbohydrate. There are m an y antibod ies available to a
variety o f epitopes. It is a h ig h ly sensitive m arker fo r adenocarci-
nom as and is therefore used w id e ly in e ffu sion cytology due to
its a b ility to disting uish adenocarcinom a fro m reactive as w e ll as
m a lig n a n t m esothelial cells. A substantial n um b er o f adenocar-
cinom as stain strong ly fo r CEA. CEA a ntib od y in effusion cytol-
ogy has a lo w se n sitivity (55 % ) and a hig h specificity (10 0% ).54
1053
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