Fig. 25.75 (A) Ductal carcinoma, nuclear grade I, demonstrating the
uniform appearance of the tumor cells with minimum enlargement; round,
small, smooth nuclear membrane; and uniform fine chromatin distribution
with no nucleoli (Papanicolaou x LP). (B) Ductal carcinoma, nuclear
grade II, characterized by larger hyperchromatic nuclei with small nucleoli
and some anisonucleosis (Papanicolaou x HP).
Hormone Receptor Determinations in Fine-Needle
Aspirates of the Breast
T he d e te rm in a tio n o f ER and PR status o f breast carcinom as is
n o w a standard practice in evaluating the h o rm o n a l depend-
ence o f breast carcinom a. Between 55 and 60% o f ER-positive
tu m o rs respond to h o rm o n a l therapy, whereas few er th a n 10%
o f negative tu m o rs respond.423-425 C urrently, IH C has become
the m eth od o f choice fo r d e term in in g the ER and PR status.425
N u m erous studies have dem onstrated th a t h o rm o n e receptors
can be evaluated on FN A specimens and cytology im p rin ts
w ith excellent c orrelation w ith the surgical p atholog y status
(Fig. 25.7 8 ).425-433 B oth fo rm a lin -fix e d and Papanicolaou-stained
(C arnoy-fixed) slides yie ld s im ila r results provided th a t antigen
retrieval was applied.434,435 A n N C I-sponsored consensus con-
ference "d e te rm ine d th a t evaluation o f prognostic and predic-
tive factors in FN A specimens o f p rim a ry breast cancer should
be largely confined to patients w h o w ill undergo neoad juvant
chem otherap y before surgery, and th e n o n ly i f CNB samples are
n o t availab le."290 T he current recom m end ation b y the College
o f A m erican Pathologists is to rep o rt ER -staining results as the
percentage o f p ositive nuclei, since the response to h o rm o n a l
therapy correlates w ith the level o f ER expression, and n o t just
Fig. 25.76 Aspirate of a locally advanced breast cancer revealing
nuclear grade III features including considerable variation in nuclear size
and shape of the tumor cells (Diff-Quik x LP).
lis tin g the results as p ositive o r negative.436 Im age analysis has
proven useful in cases o f b o rd e rlin e ER staining .437-439
In m etastatic breast carcinom a, assessment o f ER and PR is
c lin ic a lly useful because m etastatic deposits can be negative fo r
receptors w h en the p rim a ry tu m o r was p ositive o r vice versa.423
Also, ER and PR expression can also change sig n ific an tly after
preoperative chem otherapy.363,440 In contrast, H E R 2 /n eu status
is stable and n o t m od ified b y chem otherapy, therefore repeat
testing o f H ER2 is n o t needed.441
A m p lific a tio n o f the H E R 2/neu gene is the m ost im p o rta n t
genetic alteration associated w ith h u m a n breast cancer.442 Because
the clinical response to trastuzum ab (H erceptin) is best in patients
whose tum ors are positive by fluorescence in situ h yb rid iza tion
(FISH ) o r strongly positive b y IH C analysis, the current recom -
m ended approach is to use the IH C m ethod as a screening test
w ith FISH perform ed after IH C analysis, especially in the 2+ IH C
cases.443,444 Studies showed th a t H E R 2/neu oncogene am plifica-
tio n can be detected in b o th cytologic and surgical specimens,
w ith equal results.435,445-447 A rchival D iff-Q u ik-sta in ed smears o r
smears fixed w ith FISH fixatives are suitable fo r FISH analysis.448,449
Som e investigators recom m end FISH studies as the first-line anal-
ysis, because cytology m aterial can be lim ite d and m em branous
staining o f H E R 2/neu in FN A preparation is d iffic u lt to interpret.
Therefore, FISH testing is believed to be m ore reliable than IH C
analysis in cytology specimens.435,450 However, in one study, core
biopsy specimens and corresponding touch preparations showed
identical results, establishing the re lia b ility o f the use o f cytol-
ogy specimens in the evaluation o f HER2 gene a m p lific atio n.451
C hrom ogen in situ h yb rid iza tio n has been perform ed on b o th
surgical and cytology specimens w ith successful results.452,453
D N A analysis using flo w cytom etry o r image cytom etry can
be p erform ed o n FN A b iopsy specimens,454-456 a lthoug h the
value o f D N A analysis as an independent prognostic factor in
breast carcinom a has n o t been firm ly established.456 O th e r pos-
sible prognostic studies th a t have been perform ed on breast
FN A specimens include K i6 7 .457
The Breast FNA cytology Report
The N C I-sponsored conference advocated a u n ifo rm approach to
the perform ance and rep orting o f breast FN A biopsy.290 G uide-
lines fo r perform ance o f FN A o r core biopsies on palpable and
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