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Metastasis-Associated Gene Identified and May Prove Useful as Marker for Relapse

Metastasis-Associated Gene Identified and May Prove Useful as Marker for Relapse

HOUSTON—A gene that has been labeled metastasis-associated gene appears to
be related to poor disease-free survival. Investigators at Baylor College of
Medicine in Houston have produced a polyclonal antibody to
metastasis-associated tumor antigen (MTA1)-specific isotopes that may prove
useful as a prognostic marker for recurrence.

"We previously reported that markers D14S62 and D14S521 detect loss of
heterozygosity (LOH) at significantly higher rates in node-negative relative to
node-positive primary cancers (68% vs 24%; P = .001). "We have since
determined that, in addition to a presumptive tumor suppressor gene, these LOH
events encompass a metastasis-related gene (MTA1)," explained Peter O’Connell,
MD, formerly of Baylor University and now at the Medical College of Virginia in
Richmond.

MTA1 has homology to the nuclear receptor co-repressor 1 gene and is a
subunit of the nuclear remodeling and histone deacetylation complex. MTA1 is
mapped to the same gene locus, specifically the 14qter LOH metastatic locus.

An immunohistochemical assay was developed for the MTA1-specific antibody to
test formalin-fixed, paraffin-embedded archival tissue from 1,000 primary
breast tumors and control tissues with long-term follow-up in the Baylor tissue
bank.

MTA1 expression, according to immunohistochemistry staining, was positively
correlated with progesterone and estrogen receptor positivity, but was not
correlated with traditional risk factors of relapse, including lymph node
positivity, tumor size, and S phase, Dr. O’Connell reported.

"Our question then became, since MTA1 is unrelated to traditional risk
factors, is MTA1 measuring something new?" he said.

The investigators conducted a multivariate analysis of disease-free and
overall survival in 997 patients, but since strong treatment effects were seen
for chemotherapy and endocrine therapy, the current analysis was restricted to
patients who were node-negative and therefore received no treatment after
surgery.

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