title: Stromal expression of heat-shock protein 27 is associated with worse clinical outcome in patients with colorectal cancer lung metastases.
abstract: BACKGROUND
  Pulmonary metastases are common in patients with primary colorectal cancer (CRC). Heat-shock protein 27 (Hsp27) is upregulated in activated fibroblasts during wound healing and systemically elevated in various diseases. Cancer-associated fibroblasts (CAFs) are also thought to play a role as prognostic and predictive markers in various malignancies including CRC. Surprisingly, the expression of Hsp27 has never been assessed in CAFs. Therefore we aimed to investigate the expression level of Hsp27 in CAFs and its clinical implications in patients with CRC lung metastases.
  
  
  METHODS
  FFPE tissue samples from 51 pulmonary metastases (PMs) and 33 paired primary tumors were evaluated for alpha-SMA, CD31, Hsp27 and vimentin expression by immunohistochemistry and correlated with clinicopathological variables. 25 liver metastases served as control group. Moreover, serum samples (n=10) before and after pulmonary metastasectomy were assessed for circulating phospho-Hsp27 and total Hsp27 by ELISA.
  
  
  RESULTS
  Stromal expression of Hsp27 was observed in all PM and showed strong correlation with alpha-SMA (P<0.001) and vimentin (P<0.001). Strong stromal Hsp27 was associated with higher microvessel density in primary CRC and PM. Moreover, high stromal Hsp27 and αSMA expression were associated with decreased recurrence-free survival after pulmonary metastasectomy (P=0.018 and P=0.008, respectively) and overall survival (P=0.031 and P=0.017, respectively). Serum levels of phospho- and total Hsp27 dropped after metastasectomy to levels comparable to healthy controls.
  
  
  CONCLUSIONS
  Herein we describe for the first time that Hsp27 is highly expressed in tumor stroma of CRC. Stromal α-SMA and Hsp27 expressions correlate with the clinical outcome after pulmonary metastasectomy. Moreover, serum Hsp27 might pose a future marker for metastatic disease in CRC.
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
authors: Thomas
authors: T
authors: Schweiger
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
authors: Christoph
authors: C
authors: Nikolowsky
authors: Department of General Surgery, Medical University of Vienna, Vienna, Austria.
authors: Patrick
authors: P
authors: Starlinger
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
authors: Denise
authors: D
authors: Traxler
authors: Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
authors: Matthias
authors: M
authors: Zimmermann
authors: Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors: Peter
authors: P
authors: Birner
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria; 2nd Department of Pathology, Semmelweis University, Budapest, Hungary; Molecular Oncology Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary; Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Vienna, Austria.
authors: Balazs
authors: B
authors: Hegedüs
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary; Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Vienna, Austria.
authors: Balazs
authors: B
authors: Dome
authors: Department of General Surgery, Medical University of Vienna, Vienna, Austria.
authors: Michael
authors: M
authors: Bergmann
authors: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors: Michael
authors: M
authors: Mildner
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors: Walter
authors: W
authors: Klepetko
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
authors: Konrad
authors: K
authors: Hoetzenecker
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
authors: Hendrik Jan
authors: HJ
authors: Ankersmit
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; D014746:Vimentin