High level of HSF1 associates with aggressive endometrial carcinoma and suggests potential for HSP90 inhibitors.
BACKGROUND
Recent identification of a specific role of HSF1 in cancer progression has led to new relevance of HSF1 as both a prognostic and a predictive marker. The role of HSF1 in endometrial cancer has so far been unexplored.


METHODS
A total of 823 lesions from endometrial carcinoma precursors, primary tumours and metastases were prospectively collected and explored for HSF1 protein expression in relation to established markers for aggressive disease and survival. Transcriptional alterations related to HSF1 protein level were investigated by microarray analysis for 224 freshly frozen samples in parallel.


RESULTS
High expression of HSF1 protein in endometrial carcinoma is significantly associated with aggressive disease and poor survival (all P-values ≤ 0.02), also among ERα-positive patients presumed to have good prognosis. The HSF1-related gene signatures increase during disease progression and were also found to have prognostic value. Gene expression analyses identified HSP90 inhibition as a potential novel therapeutic approach for cases with high protein expression of HSF1.


CONCLUSIONS
We demonstrate for the first time in endometrial cancer that high expression of HSF1 and measures for transcriptional activation of HSF1 associate with poor outcome and disease progression. The HSP90 inhibitors are suggested as new targeted therapeutics for patients with high HSF1 levels in tumour in particular.
1] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
H
H
Engerud
1] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
I L
IL
Tangen
1] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
A
A
Berg
1] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway [3] Computational Biology Unit, University of Bergen, Bergen, Norway.
K
K
Kusonmano
1] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
M K
MK
Halle
1] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
A M
AM
Oyan
1] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
K H
KH
Kalland
Department of Pathology, Haukeland University Hospital, Bergen, Norway.
I
I
Stefansson
1] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
J
J
Trovik
1] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
H B
HB
Salvesen
1] Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
C
C
Krakstad
D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis; D011379:Prognosis; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D059467:Transcriptome
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors