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Breast Cancer Research and Treatment

, Volume 98, Issue 2, pp 231–240 | Cite as

Expression of “Spot 14” (THRSP) predicts disease free survival in invasive breast cancer: immunohistochemical analysis of a new molecular marker

  • Wendy A. Wells
  • Gary N. Schwartz
  • Peter M. Morganelli
  • Bernard F. Cole
  • Jennifer J. Gibson
  • William B. Kinlaw
Preclinical study

Summary

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.

Keywords

chromosome 11q13 gene amplification lipogenesis tumor markers 

Abbreviations

DCIS

ductal carcinoma in situ

ER

estrogen receptor

FAS

fatty acid synthase

FISH

fluorescent in situ hybridization

PCR

polymerase chain reaction

PgR

progesterone receptor

S14

spot 14

THRSP

thyroid hormone-responsive spot 14 protein

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Notes

Acknowledgements

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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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Wendy A. Wells
    • 1
    • 2
  • Gary N. Schwartz
    • 2
    • 3
  • Peter M. Morganelli
    • 2
    • 4
  • Bernard F. Cole
    • 2
    • 5
  • Jennifer J. Gibson
    • 2
    • 5
  • William B. Kinlaw
    • 2
    • 3
    • 6
  1. 1.Department of PathologyDartmouth Medical SchoolLebanonUSA
  2. 2.Norris Cotton Cancer CenterDartmouth Medical SchoolLebanonUSA
  3. 3.Department of MedicineDartmouth Medical SchoolLebanonUSA
  4. 4.US Department of Veterans AffairsVA HospitalWhite River Jct.USA
  5. 5.Department of Community and Family MedicineDartmouth Medical SchoolLebanonUSA
  6. 6.Department of Pathology, Division of endocrinology and metabolismDartmouth Medical SchoolLebanonUSA

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