Flow Cytometric DNA Analyses of Benign Breast Lesions ... · analysis of invasive breast carcinoma, and there are several reports of DNA analysis of ductal carcinoma in situ (5, 7-14).
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Vol. 4, 1543-1547, June 1998 Clinical Cancer Research 1543
Flow Cytometric DNA Analyses of Benign Breast Lesions Detected
by Screening Mammography
Paul C. Stomper,’ James R. DeBloom II,
Rose Marie Budnick, and Carleton C. Stewart
Division of Diagnostic Imaging [P. C. S.l and Department of Flow
Cytometry [R. M. B.. C. C. S.], Roswell Park Cancer Institute. Schoolof Medicine and Biomedical Sciences, State University of New Yorkat Buffalo, and Department of Natural Sciences, Roswell Park
Division of the State University of New York at Buffalo [J. R. D.J,
Buffalo, New York 14263
ABSTRACT
There is little information regarding flow cytometricDNA analyses of benign breast lesions. This prospective
study consists of mammographic and pathological correla-
tion of DNA flow cytometric analyses of specimen mammog-raphy-guided fine-needle aspirates (FNAs) of 189 consecu-tive benign breast lesions and 114 FNAs of adjacent normal
tissue as a control. Clinical follow-up was also performed.
Aneuploidy was detected in 14 of 189 (7%) benign lesion
specimen mammography-guided FNAs and in only 1 of 114
(0.9%) FNAs of adjacent normal tissue (P = 0.01). Aneu-ploidy was detected in two (33%) benign intramammarylymph nodes compared with four (12%) benign lesions withatypia, one benign lesion (3%) with hyperplasia, four benign
lesions (10%) with adenosis, and three (4%) other benign
lesions (P = 0.01). There were no significant associationsbetween DNA content and S-phase percentage and patientage, mammographic appearance, or extent. During a me-
dian follow-up of 40 months (range, 6-84 months), 2 of 13
(15%) patients with aneuploid benign lesions developed ip-
silateral breast carcinoma compared with 5 of 175 (3%)patients with diploid benign lesions (odds ratio, 6.18; 95%
confidence interval, 1.08-35.56). Our data suggest that ane-uploidy, which is detected in a variety of benign breast
lesions, may be associated with a higher risk of development
of breast carcinoma. The combined techniques of specimenmammography-guided fine-needle aspiration and flow cy-tometry provide a practical translational research method
for the study of benign breast disease.
INTRODUCTION
The increased utilization of screening mammography has
led to increased numbers of either excisional or percutaneous
Received 1/5/98; revised 3/20/98: accepted 3/23/98.The costs of publication of this article were defrayed in part by the
payment of page charges. This article must therefore be hereby marked
advertisement in accordance with I 8 U.S.C. Section 1734 solely to
indicate this fact.
I To whom requests for reprints should be addressed, at Division ofDiagnostic Imaging, Roswell Park Cancer Institute, Elm and Carlton
Streets, Buffalo, NY 14263. Phone: (716) 845-5796; Fax: (716) 845-
“ P = 0.014 comparing the aneupboid rate of intramammary lymph nodes with all other diagnoses.b Atypia/LCIS, hyperplasia, andC Intramammary lymph nodes and other benign lesions.
RESULTS
Flow cytometrie DNA analysis of specimen mammogra-
phy-guided FNAs was possible on 189 consecutive clinically
occult benign lesions that underwent excision prompted by
screening mammography. Fourteen of 189 (7%) benign lesions
contained ancuploidy. The median S-phase percentage of the
study group was 2.0; the lower 33rd percentile S-phase percent-
age was � 1.6, and the higher 33rd percentile S-phase percent-
age was �4.1 (Table 1).
DNA analysis of specimen mammography-guided FNAs in
adjacent normal mammographic tissue with benign histological
findings showed aneupboidy in only 1 of 1 14 (0.9%) eases
within the study. As shown in Table 2, the aneuploid rate in the
normal tissue control group was significantly lower than that of
the benign lesions (P = 0.01).
Associations between clinical and mammographic features
and DNA analyses of the benign lesions are shown in Table 3.
DNA content and S-phase percentage showed no significant
associations with patient age, mammographie appearance, and
mammographic soft tissue or calcification extent.
Associations between histological diagnoses and DNA
analyses of the benign lesions are shown in Table 4. Benign
histological diagnoses included nonproliferative benign lesions
fine-needle aspiration, because multiple tests can be performed
simultaneously on the same low number of cells.
In conclusion, DNA flow cytometry can be performed
successfully on specimen mammography-guided FNAs of mam-
mography-detected lesions that prove to be benign at biopsy.
Our pilot study data suggest that aneuploidy, which is seen in a
variety of benign breast lesions, is associated with a higher
short-term risk of development of ipsilaterab breast carcinoma
than benign lesions with diploidy. The combined techniques of
specimen mammography-guided FNA and flow cytometry pro-
vide a practical translational research method for the further
study and molecular and genetic risk assessment of benign
breast disease.
ACKNOWLEDGMENTS
We gratefully acknowledge Karin Brady for invaluable assistance
in data management and preparation of this manuscript and Les Blu-
menson for statistical analysis.
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1998;4:1543-1547. Clin Cancer Res P C Stomper, J R DeBloom, 2nd, R M Budnick, et al. detected by screening mammography.Flow cytometric DNA analyses of benign breast lesions