Expression of “Spot 14” (THRSP) predicts disease free survival in invasive breast cancer: immunohistochemical analysis of a new molecular marker
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Most breast cancers are “lipogenic”, defined by high fatty acid synthase (FAS) content and dependence on fatty acid synthesis for growth and survival. S14 (Spot 14; THRSP) is a nuclear protein that activates genes required for fatty acid synthesis. The S14 gene is amplified in ~15% of breast cancers, but clinical correlates of its expression were unknown. We analyzed 131 breast cancers by immunohistochemistry for S14 and FAS. Staining was graded 0, 1, or 2+, and scores were correlated with traditional tumor markers, histological features, and outcome. S14 and FAS staining were related to tumor size (p=0.05 for S14, p=0.038 for FAS), but not to stage. S14 but not FAS scores correlated with tumor grade in both DCIS (p=0.003) and invasive cases (p<0.001). Invasive cases (pooled node − and +) with weak S14 staining (n=21) showed no recurrence over 3000 d follow-up, including 10 cases with lymph node involvement, whereas 32% of 67 strongly-staining tumors recurred (log rank p<0.0001). S14 scores did not cosegregate with sex steroid receptors, Her2/neu, or cyclin D1. Low level S14 expression is associated with prolonged disease-free survival in invasive cases, including those with nodal metastasis. High-level expression of S14 identifies a subset of high-risk breast cancers that is not specified by analysis of sex steroid receptors, Her2/neu, or cyclin D1, and provides a molecular correlate to histologic features that predict recurrence.
Keywordschromosome 11q13 gene amplification lipogenesis tumor markers
ductal carcinoma in situ
fatty acid synthase
fluorescent in situ hybridization
polymerase chain reaction
thyroid hormone-responsive spot 14 protein
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We thank Dr. Vincent Memoli for consultation regarding immunohistochemistry, Ms. Maudine Waterman for performing the immunostaining, and Drs. Murray Korc and Mark Schneider for critical readings of the manuscript.
Grant support. NIH RO1 DK 058961 (to W.B.K.), and U.S. Department of Defense grant DAMD17–03-1-0544 (to W.B.K.).
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