The melanoma-associated antigen-A3, -A4 genes: relation
to the risk and clinicopathological parameters in breast
cancer patients
Yousri M. Hussein
•
Amal F. Gharib
•
Rasha L. Etewa
•
Amal S. El-Shal
•
Mohamed Esmat Abdel-Ghany
•
Wael H. Elsawy
Received: 6 November 2010 / Accepted: 10 January 2011 / Published online: 25 January 2011
Ó Springer Science+Business Media, LLC. 2011
Abstract This study aimed to evaluate the clinical reli-
ability and accuracy of two MAGE transcripts (MAGE-A3,
MAGE-A4 mRNA) in the peripheral blood (PB) of patients
with breast cancer (BC), and to evaluate their potential
limits and utility to detect BC. We aimed also to analyze
their relation to clinicopathological characteristics of the
tumor. This study is a prospective, controlled, double-
blinded study conducted on 100 BC women and 100 age-
matched control women. There were 52 patients with
localized breast mass with no evidence of nodal affection
or distant metastases and 48 patients suffering from met-
astatic BC. MAGE-A3 and MAGE-A4 mRNA in the PB
were assayed using reverse transcriptase–polymerase chain
reaction (RT-PCR). None of the control women was
positive for either MAGE-A3, MAGE-A4. In BC women,
positivity for MAGE-A3 in PB was observed in 37 patients
(37%), and MAGE-A4 positivity was observed in 11
patients (11%); with 100% specificity for both transcripts.
The presence of MAGE-A3 was significantly associated
with nodal status (P = 0.009), tumor size (P = 0.009), and
American Joint Committee on Cancer stage (P = 0.009),
whereas MAGE-A4 positivity was significantly associated
with histological grade (P = 0.020). RT-PCR assays of
MAGE-A3 and MAGE-A4 in the PB of BC patients may
have prognostic and predictive implications, and they are
promising specific tumor markers of BC.
Keywords Breast cancer Á MAGE-A3 and MAGE-A4 Á
Neoplasm metastasis
Introduction
Breast cancer (BC) continues to be one of the most com-
mon cancers and a major cause of death among women
worldwide [1]; therefore, early detection is one of the most
critical factors for a favorable outcome [2]. Despite recent
progress in early detection and apparent curative resection,
subsequent development of metastatic spread presents a
major clinical problem, primarily because the occult dis-
semination of cancer cells can occur at an early stage of
carcinogenesis [3]. Tumor cells in peripheral blood (PB)
are capable of clonogenic growth in vitro, thus possibly
participating in recurrence [4]. Few diagnostic tools are
available to identify the patients at risk, and there is a need
for relevant prognostic and predictive factors with proven
clinical utility to assess an individual patient’s risk of
disease recurrence [5, 6].
Various molecular markers including CEA, CK-19, and
Muc1 have been proposed to detect circulating BC cells in
PB. Most of these are poorly specific for tumor cells, and
transcripts are occasionally detected in the blood and
lymph nodes of healthy volunteers [7–11]. Moreover,
breast tumors are composed of heterogenous cells with
different levels of gene expression. Gene expression anal-
ysis provides a potentially easy and noninvasive approach,
and more accurate than existing markers [12]. It has been
suggested that the combination of different markers may
Y. M. Hussein Á A. F. Gharib Á R. L. Etewa (&) Á A. S. El-Shal
Department of Medical Biochemistry, Zagazig University,
Zagazig 44519, Egypt
e-mail: rashalotfi@yahoo.co.uk
M. E. Abdel-Ghany
Department of General Surgery, Al-Azhar University,
Cairo, Egypt
W. H. Elsawy
Department of Clinical Oncology and Nuclear Medicine,
Zagazig University, Zagazig 44519, Egypt
123
Mol Cell Biochem (2011) 351:261–268
DOI 10.1007/s11010-011-0734-4