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Diagnostic and prognostic utility of molecular markers in synchronous bilateral breast carcinoma
Journal article   Open access   Peer reviewed

Diagnostic and prognostic utility of molecular markers in synchronous bilateral breast carcinoma

Reda S Saad, Krista L Denning, Sydney D Finkelstein, Yulin Liu, Telma C Pereira, Xiaoqi Lin and Jan F Silverman
Modern pathology, v 21(10), pp 1200-1207
Oct 2008
DOI: https://doi.org/10.1038/modpathol.2008.35
PMID: 18469799
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1038/modpathol.2008.35View
Published, Version of Record (VoR)Open Access (Publisher-Specific),  Open

Abstract

Aged Aged, 80 and over Biomarkers, Tumor - metabolism Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Carcinoma, Ductal, Breast - genetics Carcinoma, Ductal, Breast - metabolism Carcinoma, Ductal, Breast - secondary DNA Mutational Analysis Female Genetic Markers - genetics Humans Loss of Heterozygosity Lymphatic Metastasis Mastectomy Microsatellite Repeats Middle Aged Neoplasms, Multiple Primary - genetics Neoplasms, Multiple Primary - metabolism Neoplasms, Multiple Primary - pathology Prognosis Receptor, ErbB-2 - metabolism Receptors, Steroid - metabolism
Histologic criteria have a limited role in determining whether the synchronous bilateral breast carcinomas represent two primaries or a metastasis to the contralateral breast. We studied the molecular analysis of synchronous bilateral breast carcinoma and whether they are originating from a single or different clone. We examined 17 patients with breast carcinoma, including 12 patients with synchronous bilateral carcinomas and control group of 5 infiltrating ductal carcinomas with regional lymph node metastases. Mutations were quantitatively determined to detect loss of heterozygosity (LOH) and microsatellite size alterations for a broad panel of 15 markers, involving 10 chromosomes using polymerase chain reaction. The carcinomas were classified as de novo or metastasis based on three levels of concordance: (1) marker-affected tumors were considered concordant if 50% or more of the same markers were mutated, (2) same gene copy affected, and (3) temporal sequence of mutation acquisition. In synchronous bilateral breast carcinoma patients, molecular analysis showed discordant mutations in all cases, supporting the diagnosis of de novo bilateral primary breast carcinomas. In patients with lymph node metastases, the primary breast carcinoma and metastases shared the same mutations, revealing a metastatic lesion. In conclusion, the application of molecular technology may play an important role for the differential diagnosis of dual primary carcinomas vs a metastatic breast cancer to contralateral breast. In this study, synchronous bilateral breast cancers represent two independent primaries rather than metastatic events.

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26 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Pathology
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