Flow Cytometric DNA Analysis of Invasive Carcinomas ... · 1790 Flow Cytometric DNA Analysis of Invasive Carcinomas using FNAs at pathological exam. The median age of the patients
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Vol. 4, 1789-1795, July 1998 Clinical Cancer Research 1789
Flow Cytometric DNA Analysis of Invasive Carcinomas Detected by
Screening Mammography: Use of Specimen Mammography-guided
Fine-Needle Aspirates
Paul C. Stomper,’ James R. DeBloom II,
Ellis Levine, Rose Marie Budnick, and
Carleton C. StewartDivision of Diagnostic Imaging [P. C. S.], Department of Medicine
[E. L.], and Department of Flow Cytometry, Division of Pathology[R. M. B., C. C. S.], Roswell Park Cancer Institute, School ofMedicine and Biomedical Sciences, State University of New York atBuffalo, and Department of Natural Sciences, Roswell Park Divisionof State University of New York at Buffalo [J. R. D.], Buffalo, NewYork 14263
ABSTRACTClinical studies of flow cytometric DNA analysis of
breast carcinoma are often limited by the lack of fresh tissue
samples from smaller, nonpalpable carcinomas. In addition,
most studies measuring DNA in the current literature focus
on larger palpable masses that may have less relevance to
the smaller, nonpalpable lesions. A prospective study of flow
cytometric DNA analysis of in vitro specimen mammogra-
phy-guided fine-needle aspirates (FNAs) of 103 consecutive
nonpalpable invasive carcinomas detected by screening
mammography was performed to determine efficacy and
explore associations with mammographic and pathological
features. For 62 (60%) lesions for which DNA analysis on
both FNA and standard tissue incision samples was per-
formed, there was excellent (89%) agreement for ploidy
determinations (K = 0.77) and poor agreement for S-phase
therapy in node-negative breast cancer patients have increased
the need for better prognostic assessment for these early lesions.
DNA ploidy and S-phase percentage are among the prognostic
markers that are being evaluated for invasive breast carcinomas.
Prior clinical studies suggest that S-phase percentage has greater
prognostic significance than does aneuploidy (1-19). However,
clinical studies of flow cytometric DNA analysis are often
limited by the lack of fresh tissue samples from smaller invasive
carcinomas detected by screening mammography, resulting in a
lack of understanding of the prognostic significance of this test
in an increasingly relevant group of patients.
We have been performing flow cytometric DNA analysis
on specimen mammography-guided FNAs2 of lesions within
excised breast specimens after wire localization and surgical
excision of clinically occult lesions detected by mammography
(20, 21). To our knowledge, there is little information in the
literature regarding flow cytometric DNA analysis of clinically
occult invasive breast carcinomas using this technique of pro-
curement of mammographic lesion-specific fresh cell samples.
There are also little published data regarding mammographic
and pathological associations with flow cytometric DNA anal-
ysis features of screening-detected nonpalpable invasive breast
carcinomas.
This prospective pilot study was undertaken to determine
the DNA ploidy and S-phase percentage of specimen mammog-
raphy-guided FNAs of screening mammography-detected inva-
sive carcinomas by flow cytometry and to explore associations
between mammographic and pathological features with ploidy
and S-phase percentages.
Received 3/5/98; revised 4/7/98; accepted 4/28/98.The costs of publication of this article were defrayed in part by the
payment of page charges. This article must therefore be hereby markedadvertisement in accordance with 18 U.S.C. Section 1734 solely toindicate this fact.
I To whom requests for reprints should be addressed, at Division ofDiagnostic Imaging, Roswell Park Cancer Institute, Elm and CantonStreets, Buffalo, NY 14263. Phone: (716) 845-5796; Fax: (716) 845-8796; E-mail: [email protected].
MATERIALS AND METHODS
The study group consists of 103 consecutive patients who
underwent biopsies of clinically occult lesions detected by
screening mammography that showed invasive breast carcinoma
2 The abbreviations used are: FNA, fine-needle aspirate; DCIS, ductal
a For stellate masses, the central mass diameter was used.b NS, not significant.C Pathological tumor size was difficult to assess for three lesions.d Values shown are for 64 patients who underwent axillary node dissection.e Receptor assays were not performed on I 8 lesions.
DNA analysis of in vivo stereotactic FNA and in vitro FNA
of frozen tissue samples of nonpalpable breast carcinomas has
been performed using microspectrophotometry (27, 28). DNA
flow cytometry has been performed on paraffin-embedded tis-
sue and fresh tissue samples, needle aspirates, or scrapings from
larger tumors that were palpable at clinical or pathological exam
(5, 18, 20, 29-35). We and other investigators prefer fresh
tissue, rather than paraffin-embedded tissue, because the fixa-
tion process may render the analysis less accurate (36-38).
Aside from the advantages of providing mammographic lesion-
specific fresh cell samples for clinically occult lesions, the
1794 Flow Cytometric DNA Analysis of Invasive Carcinomas using FNAs
between DNA analysis and mammographic features increase
our understanding of the mammographic features of early inva-
sive carcinomas. We feel that this technique of mammographic
lesion-specific fresh cell procurement is easy to perform, and
that the flow cytometric DNA analysis data obtained can stratify
early invasive breast carcinomas and could be incorporated into
larger clinical trials to ultimately determine the prognostic sig-
nificance of the findings.
ACKNOWLEDGMENTS
We gratefully acknowledge Karin Brady for invaluable assistance
in data management and preparation of the manuscript and Les Blu-menson for statistical analysis.
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