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Histochemistry and Cell Biology

, Volume 138, Issue 1, pp 141–154 | Cite as

The C-terminal fragment of the immunoproteasome PA28S (Reg alpha) as an early diagnosis and tumor-relapse biomarker: evidence from mass spectrometry profiling

  • Rémi Longuespée
  • Charlotte Boyon
  • Céline Castellier
  • Amélie Jacquet
  • Annie Desmons
  • Olivier Kerdraon
  • Denis Vinatier
  • Isabelle Fournier
  • Robert Day
  • Michel SalzetEmail author
Original Paper

Abstract

This study reports on the C-terminal fragment of the 11S proteasome activator complex (PA28 or Reg alpha), a novel ovarian-specific biomarker of early and late stages of ovarian cancer (OVC) relapse, in patient biopsies after chemotherapy. A total of 179 tissue samples were analyzed: 8 stage I, 55 stage III–IV, 10 relapsed serous carcinomas, 25 mucinous carcinomas and 12 borderline and 68 benign ovarian tissue samples. This fragment was detected by MALDI mass spectrometry profiling in conjunction with a novel extraction method using hexafluoroisopropanol (1,1,1,3,3,3-hexafluoro-2-propanol; HFIP) solvents for protein solubilization and by immunohistochemistry using a specific antibody directed against the C-terminal fragment of PA28. Due to its specific cellular localization, this fragment is a suitable candidate for early OVC diagnosis, patient prognosis and follow-up during therapy and discriminating borderline cancers. Statistical analyses performed for this marker at different OVC stages reflect a prevalence of 77.66 ± 8.77 % (with a correlation coefficient value p < 0.001 of 0.601 between OVC and benign tissue). This marker presents a prevalence of 88 % in the case of tumor relapse and is detected at 80.5 % in stage I and 81.25 % ± 1.06 in stage III–IV of OVC. The correlation value for the different OVC stages is p < 0.001 of 0.998. Taken together, this report constitutes the first evidence of a novel OVC-specific marker.

Keywords

Ovarian cancer MALDI imaging Biomarker Relapse Diagnostic Mass spectrometry 

Notes

Acknowledgments

This study was supported by grants from the Agence Nationale de la Recherche (ANR PCV to IF), Institut du Cancer (INCA to IF), Institut de Recherche en Santé du Canada (ISRC to MS & RD), Ministère du Développement Économique de l’Innovation et de l’Exportation (MDEIE to R.D), Fonds de recherche du Québec-Santé (FRQS to R.D), C.H.R. U. Lille (to CB) and Région Nord-Pas de Calais (to RL). R.D. is a member of the Centre de Recherche Clinique Etienne-Le Bel (Sherbrooke, QC, Canada).

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Rémi Longuespée
    • 1
    • 4
  • Charlotte Boyon
    • 1
    • 2
  • Céline Castellier
    • 1
    • 2
  • Amélie Jacquet
    • 1
    • 2
  • Annie Desmons
    • 1
  • Olivier Kerdraon
    • 3
  • Denis Vinatier
    • 1
    • 2
  • Isabelle Fournier
    • 1
  • Robert Day
    • 4
  • Michel Salzet
    • 1
    Email author
  1. 1.Laboratoire de Spectrométrie de Masse Biologique Fondamentale et AppliquéeUniversité Nord de France, EA 4550, Université de Lille 1, Cité ScientifiqueVilleneuve D’AscqFrance
  2. 2.Hôpital Jeanne de Flandre, Service de Chirurgie Gynécologique, CHRU LilleLille CedexFrance
  3. 3.Laboratoire d’Anatomie et de Cytologie Pathologiques, CHU LilleLille CedexFrance
  4. 4.Institut de Pharmacologie de SherbrookeUniversité de SherbrookeSherbrookeCanada

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