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Possible predictors of histopathological response to neoadjuvant chemoradiotherapy for rectal cancer

  • Robert Farkas
  • Eva Pozsgai
  • Andrew V. Schally
  • Andras Szigeti
  • Edit Szigeti
  • Zoltan Laszlo
  • Andras Papp
  • Eva Gomori
  • Laszlo Mangel
  • Peter O. Horvath
  • Szabolcs Bellyei
Original Paper

Abstract

Purpose

The response to neoadjuvant chemoradiotherapy (CRT) varies greatly in patients suffering from locally advanced rectal cancer. Our aim was to correlate the response to CRT with the pre-treatment expression of heat shock protein 90 (Hsp90), small heat shock protein 16.2 (sHsp 16.2), phospho-Akt (p-Akt), growth hormone–releasing hormone receptor (GHRH-R) and heme-binding protein 2 (SOUL) in order to try to identify one or more as a predictive marker.

Materials and methods

Sixty-nine patients receiving combined CRT for locally advanced rectal cancer were examined retrospectively. Surgical resection was carried out 6–9 weeks following CRT. The histopathological response to neoadjuvant treatment was determined according to the modified Mandard score. Using immunohistochemistry, we investigated the relationship between the expression of the five cited proteins in the pre-operative samples as well as various clinical parameters and the histopathological regression of the tumors.

Results

Thirty-one patients (48%) were good responders, and 33 patients (52%) were found to respond poorly to neoadjuvant therapy. Among patients undergoing surgery 7 weeks following CRT, there were significantly more good responders than among patients who underwent surgery sooner (63% vs. 37%). High levels of expression of GHRH-R and Hsp90 were shown to be significantly correlated with minor or absent histological regression.

Conclusions

GHRH-R and Hsp90 were found to be independent predictive factors of histopathological response to neoadjuvant RCT. Since GHRH-R antagonists and Hsp90 inhibitors are currently being tested as potential anticancer agents, our study implies the possible elaboration of an effective and individualized treatment of poor responders.

Keywords

Neoadjuvant chemoradiotherapy Rectal cancer Hsp90 GHRH-R Predictive marker of tumor regression Prediction of response 

Notes

Acknowledgments

This work was supported by a grant from the Hungarian Science Foundation 68469, by Research Grants from the Ministry of Health (2006–2008; 01/270) and by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences and Research Grants from AOKKA-34039-1004/2010.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Robert Farkas
    • 1
  • Eva Pozsgai
    • 2
  • Andrew V. Schally
    • 3
  • Andras Szigeti
    • 1
  • Edit Szigeti
    • 2
  • Zoltan Laszlo
    • 1
  • Andras Papp
    • 4
  • Eva Gomori
    • 5
  • Laszlo Mangel
    • 1
  • Peter O. Horvath
    • 4
  • Szabolcs Bellyei
    • 1
  1. 1.Department of OncologyUniversity of PécsPecsHungary
  2. 2.Department of Biochemistry and Medical ChemistryUniversity of PécsPecsHungary
  3. 3.Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and EducationMiamiUSA
  4. 4.Department of SurgeryUniversity of PécsPecsHungary
  5. 5.Department of PathologyUniversity of PécsPecsHungary

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