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A
novel five-antibody immunohistochemical test for subclassification of
lung carcinoma.
Mod Pathol. 2009 Aug;22(8):1032-43
B. Z. Ring2,
R. Seitz1,
R. A. Beck1,
W. Shasteen1, A.
Soltermann3, S.
Arbogast3,
F. Robert4, M. T. Schreeder5, and D. T. Ross2
1 Applied
Genomics, Inc, Huntsville, AL and 2
Burlingame, CA, 3 Universitätsspital
Zürich, Zürich, Switzerland, 4
University of Alabama Birmingham, Birmingham, AL,
5 Clearview
Cancer Center,
Huntsville, AL
Abstract
Malignant epithelial lung carcinoma can be
subclassified by histology
into several tumor types, including adenocarcinoma and squamous cell
carcinoma. The need for a uniform method of classifying lung carcinomas
is growing as clinical trials reveal treatment and side effect
differences associated with histological subtypes. Diagnosis is
primarily performed by morphological assessment. However, the increased
use of needle biopsy has diminished the amount of tissue available for
interpretation. These changes in how lung carcinomas are diagnosed and
treated suggest that the development of improved molecular-based
classification tools could improve patient management.
We used a
551-patient surgical specimen lung carcinoma retrospective cohort from
a regional hospital to assess the association of a large number of
proteins with histological type by immunohistochemistry. Five of these
antibodies, targeting the proteins TRIM29, CEACAM5, SLC7A5, MUC1, and
CK5/6, were combined into one test using a weighted algorithm trained
to discriminate adenocarcinoma from squamous cell carcinoma.
Antibody-based classification on 600 muM tissue array cores with the
five-antibody test was compared to standard histological evaluation on
surgical specimens in three independent lung carcinoma cohorts
(combined population of 1111 patients). In addition, the five-antibody
test was tested against the two-marker panel thyroid transcription
factor-1 (TTF-1) and TP63.
Both the five-antibody test and TTF-1/TP63
panel had similarly low misclassification rates on the validation
cohorts compared to morphological-based diagnosis (4.1 vs 3.5%).
However the percentage of patients remaining unclassifiable by
TTF-1/TP63 (22%, 95% CI: 20-25%) was twice that of the five-antibody
test (11%, 95% CI: 8-13%). The results of this study suggest the
five-antibody test may have an immediate function in the clinic for
helping pathologists distinguish lung carcinoma histological types. The
results also suggest that if validated in prospectively defined
clinical trials this classifier might identify candidates for targeted
therapy that are overlooked with current diagnostic approaches.
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