title: Possible predictors of histopathological response to neoadjuvant chemoradiotherapy for rectal cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Oncology, University of Pécs, Edesanyak street 17, 7624 Pecs, Hungary.
authors.forename: Robert
authors.initials: R
authors.lastname: Farkas
authors.forename: Eva
authors.initials: E
authors.lastname: Pozsgai
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.forename: Andras
authors.initials: A
authors.lastname: Szigeti
authors.forename: Edit
authors.initials: E
authors.lastname: Szigeti
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Laszlo
authors.forename: Andras
authors.initials: A
authors.lastname: Papp
authors.forename: Eva
authors.initials: E
authors.lastname: Gomori
authors.forename: Laszlo
authors.initials: L
authors.lastname: Mangel
authors.forename: Peter O
authors.initials: PO
authors.lastname: Horvath
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Bellyei
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis*; D050888:Heat-Shock Proteins, Small / Q000032:analysis; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D011237:Predictive Value of Tests; D011257:Pregnancy Proteins / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D018013:Receptors, Neuropeptide / Q000032:analysis*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000032:analysis*; D012004:Rectal Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C516258:HEBP2 protein, human; D018841:HSP90 Heat-Shock Proteins; D050888:Heat-Shock Proteins, Small; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D011257:Pregnancy Proteins; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D051057:Proto-Oncogene Proteins c-akt; C048250:somatotropin releasing hormone receptor