Skip to main content
SpringerLink
Log in

Gland Size Is Associated With Changes in Gene Expression Profiles in Sporadic Parathyroid Adenomas

  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Sporadic parathyroid adenomas (SPAs) are benign neoplasms responsible for most cases of primary hyperparathyroidism (pHPT). The molecular pathways responsible for the variations in clinical severity of pHPT are unknown. We studied gene expression profiles in patients with SPAs and pHPT to determine associations between these changes and clinical parameters.

Methods

We selected 10 patients with solitary SPAs and nonfamilial, non-MEN1 pHPT treated with surgery from 2001 to 2003. Pathologic and clinical data were reviewed. At operation, tissues from SPAs were frozen in liquid nitrogen; total RNA was obtained from sections, and the diagnosis was confirmed with hematoxylin and eosin staining. Control normal parathyroid RNA was age- and sex-matched. RNA was amplified, labeled, and hybridized to a microarray of 22,272 human oligonucleotides. Cluster analysis of gene expression, analysis of expression ratios, and comparison of clinical parameters were performed.

Results

All patients were cured; all specimens were consistent with SPAs. K means clustering divided the 10 patients into 2 distinct 5-patient gene expression groups by using uncentered correlation based on gene subgrouping. Of the clinical parameters, only the mean gland volume was significantly different between group 1 (390 ± 160 mm3) and group 2 (1080 ± 615 mm3; P = .032 by Mann-Whitney test). Seventy-five genes were significantly upregulated or downregulated (with a ratio of <.33 or >3) compared with controls. These genes included the v-fos viral oncogene homolog and six calcium ion-binding signaling proteins.

Conclusions

Differential expression of a few critical genes may contribute to differences in gland volume in SPAs. A better understanding of these pathways may help to define the pathophysiology of pHPT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig 1

Similar content being viewed by others

References

  1. S Miedlich K Krohn R Paschke (2003) ArticleTitleUpdate on genetic and clinical aspects of primary hyperparathyroidism Clin Endocrinol 59 539–54 Occurrence Handle10.1046/j.1365-2265.2003.t01-1-01755.x Occurrence Handle1:CAS:528:DC%2BD3sXpsF2ju7s%3D

    Article  CAS  Google Scholar 

  2. PP Schachter S Ayesh T Schneider M Laster A Czerniak A Hochberg (2002) ArticleTitleExpression of kinase genes in primary hyperparathyroidism: adenoma versus hyperplastic parathyroid tissue Surgery 132 1094–9 Occurrence Handle10.1067/msy.2002.128614 Occurrence Handle12490860

    Article  PubMed  Google Scholar 

  3. A Stojadinovic A Hoos A Nissan et al. (2003) ArticleTitleParathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis Hum Pathol 34 54–64 Occurrence Handle10.1053/hupa.2003.55 Occurrence Handle12605367

    Article  PubMed  Google Scholar 

  4. LM Staudt (2002) ArticleTitleGene expression profiling of lymphoid malignancies Annu Rev Med 53 303–18 Occurrence Handle10.1146/annurev.med.53.082901.103941 Occurrence Handle1:CAS:528:DC%2BD38Xitl2mtrY%3D Occurrence Handle11818476

    Article  CAS  PubMed  Google Scholar 

  5. MJ Vijver ParticleVan de YD He LJ van’t Veer et al. (2002) ArticleTitleA gene-expression signature as a predictor of survival in breast cancer N Engl J Med 347 1999–2009 Occurrence Handle10.1056/NEJMoa021967 Occurrence Handle12490681

    Article  PubMed  Google Scholar 

  6. A Schulze J Downward (2001) ArticleTitleNavigating gene expression using microarrays—a technology review Nat Cell Biol 3 E190–5 Occurrence Handle10.1038/35087138 Occurrence Handle1:CAS:528:DC%2BD3MXmtFens7k%3D Occurrence Handle11483980

    Article  CAS  PubMed  Google Scholar 

  7. G Sauter R Simon (2002) ArticleTitlePredictive molecular pathology N Engl J Med 347 1995–6 Occurrence Handle10.1056/NEJMp020155 Occurrence Handle12490679

    Article  PubMed  Google Scholar 

  8. R Simon MD Radmacher K Dobbin LM McShane (2003) ArticleTitlePitfalls in the use of DNA microarray data for diagnostic and prognostic classification J Natl Cancer Inst 95 14–8 Occurrence Handle1:CAS:528:DC%2BD3sXitlOntrY%3D Occurrence Handle12509396 Occurrence Handle10.1093/jnci/95.1.14

    Article  CAS  PubMed  Google Scholar 

  9. TR Golub DK Slonim P Tamayo et al. (1999) ArticleTitleMolecular classification of cancer: class discovery and class prediction by gene expression monitoring Science 286 531–7 Occurrence Handle10.1126/science.286.5439.531 Occurrence Handle1:CAS:528:DyaK1MXmvVOhu7g%3D Occurrence Handle10521349

    Article  CAS  PubMed  Google Scholar 

  10. LD Miller P Long L Wong S Mukherjee LM McShane ET Liu (2002) ArticleTitleOptimal gene expression analysis by microarrays Cancer Cell 2 353–61 Occurrence Handle10.1016/S1535-6108(02)00181-2 Occurrence Handle1:CAS:528:DC%2BD38Xptlalur4%3D Occurrence Handle12450790

    Article  CAS  PubMed  Google Scholar 

  11. S Raychaudhuri PD Sutphin JT Chang RB Altman (2001) ArticleTitleBasic microarray analysis: grouping and feature reduction Trends Biotechnol 19 189–93 Occurrence Handle10.1016/S0167-7799(01)01599-2 Occurrence Handle1:CAS:528:DC%2BD3MXisF2nurY%3D Occurrence Handle11301132

    Article  CAS  PubMed  Google Scholar 

  12. J Eberwine (1996) ArticleTitleAmplification of mRNA populations using aRNA generated from immobilized oligo(dT)-T7 primed cDNA Biotechniques 20 584–91 Occurrence Handle1:CAS:528:DyaK28XitFelsL0%3D Occurrence Handle8800675

    CAS  PubMed  Google Scholar 

  13. AL Feldman NG Costouros E Wang et al. (2002) ArticleTitleAdvantages of mRNA amplification for microarray analysis Biotechniques 33 906–12 Occurrence Handle1:CAS:528:DC%2BD38XnvFGrtLk%3D Occurrence Handle12398200

    CAS  PubMed  Google Scholar 

  14. E Wang LD Miller GA Ohnmacht ET Liu FM Marincola (2000) ArticleTitleHigh-fidelity mRNA amplification for gene profiling Nat Biotechnol 18 457–9 Occurrence Handle10.1038/74546 Occurrence Handle1:CAS:528:DC%2BD3cXis1GlsLo%3D Occurrence Handle10748532

    Article  CAS  PubMed  Google Scholar 

  15. AE Grigoriadis ZQ Wang MG Cecchini et al. (1994) ArticleTitleC-fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling Science 266 443–8 Occurrence Handle1:CAS:528:DyaK2cXmslyisr8%3D Occurrence Handle7939685

    CAS  PubMed  Google Scholar 

  16. AE Grigoriadis ZQ Wang EF Wagner (1995) ArticleTitleFos and bone cell development: lessons from a nuclear oncogene Trends Genet 11 436–41 Occurrence Handle10.1016/S0168-9525(00)89142-8 Occurrence Handle1:CAS:528:DyaK2MXptVant7g%3D Occurrence Handle8578600

    Article  CAS  PubMed  Google Scholar 

  17. C Dony P Gruss (1987) ArticleTitleProto-oncogene c-fos expression in growth regions of fetal bone and mesodermal web tissue Nature 328 711–4 Occurrence Handle10.1038/328711a0 Occurrence Handle1:STN:280:DyaL2s3oslarsw%3D%3D Occurrence Handle3614378

    Article  CAS  PubMed  Google Scholar 

  18. SG Isler S Schenk I Bendik et al. (2001) ArticleTitleGenomic organization and chromosomal mapping of SPARC-like 1, a gene down regulated in cancers Int J Oncol 18 521–6 Occurrence Handle1:CAS:528:DC%2BD3MXhsFGltrg%3D Occurrence Handle11179481

    CAS  PubMed  Google Scholar 

  19. CS Lin T Park ZP Chen J Leavitt (1993) ArticleTitleHuman plastin genes. Comparative gene structure, chromosome location, and differential expression in normal and neoplastic cells J Biol Chem 268 2781–92 Occurrence Handle1:CAS:528:DyaK3sXhs1ahtbk%3D Occurrence Handle8428952

    CAS  PubMed  Google Scholar 

  20. JF Tait M Sakata BA McMullen et al. (1988) ArticleTitlePlacental anticoagulant proteins: isolation and comparative characterization of four members of the lipocortin family Biochemistry 27 6268–76 Occurrence Handle10.1021/bi00417a011 Occurrence Handle1:CAS:528:DyaL1cXls1Gqsro%3D Occurrence Handle2975506

    Article  CAS  PubMed  Google Scholar 

  21. M Streit L Riccardi P Velasco et al. (1999) ArticleTitleThrombospondin-2: a potent endogenous inhibitor of tumor growth and angiogenesis Proc Natl Acad Sci U S A 96 14888–93 Occurrence Handle10.1073/pnas.96.26.14888 Occurrence Handle1:CAS:528:DC%2BD3cXhtFanug%3D%3D Occurrence Handle10611308

    Article  CAS  PubMed  Google Scholar 

  22. K Komatsu K Murata M Kameyama et al. (2002) ArticleTitleExpression of S100A6 and S100A4 in matched samples of human colorectal mucosa, primary colorectal adenocarcinomas and liver metastases Oncology 63 192–200 Occurrence Handle10.1159/000063812 Occurrence Handle1:CAS:528:DC%2BD38XntFegtLk%3D Occurrence Handle12239456

    Article  CAS  PubMed  Google Scholar 

  23. HL Hsieh BW Schafer JA Cox CW Heizmann (2002) ArticleTitleS100A13 and S100A6 exhibit distinct translocation pathways in endothelial cells J Cell Sci 115 3149–58 Occurrence Handle1:CAS:528:DC%2BD38XmsFaku7g%3D Occurrence Handle12118070

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Surgery Branch, National Cancer Institute, Building 10, Room 4W-5940, 10 Center Drive, Bethesda, Maryland, 20892

    Jennifer E. Rosen MD, Nick G. Costouros MD, Dominique Lorang PhD, A. Lee Burns MD, H. Richard Alexander MD, James F. Pingpank MD & Steven K. Libutti MD

  2. Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892

    Monica C. Skarulis BA, Craig Cochran BA, Stephen J. Marx MD & Allen M. Spiegel MD

Authors
  1. Jennifer E. Rosen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nick G. Costouros MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dominique Lorang PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Lee Burns MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Richard Alexander MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Monica C. Skarulis BA
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Craig Cochran BA
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. James F. Pingpank MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stephen J. Marx MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Allen M. Spiegel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Steven K. Libutti MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steven K. Libutti MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rosen, J.E., Costouros, N.G., Lorang, D. et al. Gland Size Is Associated With Changes in Gene Expression Profiles in Sporadic Parathyroid Adenomas. Ann Surg Oncol 12, 412–416 (2005). https://doi.org/10.1245/ASO.2005.03.103

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/ASO.2005.03.103

Keywords

Search

Navigation