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 includ-

ing CRC. Surprisingly, the expression of Hsp27 has never been assessed in CAFs. There-

fore we aimed to investigate the expression level of Hsp27 in CAFs and its clinical

implications in patients with CRC lung metastases

Ankersmit, Hendrik Jan

Bergmann, Michael

Birner, Peter

Dome, Balazs

Hegedüs, Balazs

Hoetzenecker, Konrad

Klepetko, Walter

Mildner, Michael

Multhoff, Gabriele

Nikolowsky, Christoph

Schweiger, Thomas

Starlinger, Patrick

Traxler, Denise

Zimmermann, Matthias

PLoS ONE

English

PubMed

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.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.=0.017, respectively). Serum levels of phospho- and total Hsp27 dropped after metastasectomy to levels comparable to healthy controls.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

Schweiger Thomas

Nikolowsky Christoph

Starlinger Patrick

Traxler Denise

Zimmermann Matthias

Birner Peter

Hegedüs Balazs

Dome Balazs

Bergmann Michael

Mildner Michael

Klepetko Walter

Hoetzenecker Konrad

Ankersmit Hendrik Jan

Public Library of Science (PLOS)

Stromal Expression of Heat-Shock Protein 27 Is Associated with Worse Clinical Outcome in Patients with Colorectal Cancer Lung Metastases

Schweiger T

Nikolowsky C

Starlinger P

Traxler D

Zimmermann M

Birner P

Hegedűs, Balázs

Döme, Balázs

Bergmann M

Mildner M

Klepetko W

Hoetzenecker K

Ankersmit HJ

Semmelweis Repository

Repository of the Academy's Library

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 SMA 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 -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.(VLID)491221

Nikolowksky, Christoph

MedUni Wien ePub

PLOS One / Stromal Expression of Heat-Shock Protein 27 Is Associated with Worse Clinical Outcome in Patients with Colorectal Cancer Lung Metastases

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.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.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.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

Thomas Schweiger

Christoph Nikolowsky

Patrick Starlinger

Denise Traxler

Matthias Zimmermann

Peter Birner

Balazs Hegedüs

Balazs Dome

Michael Bergmann

Michael Mildner

Walter Klepetko

Konrad Hoetzenecker

Hendrik Jan Ankersmit

Directory of Open Access Journals

Stromal expression of heat-shock protein 27 is associated with worse clinical outcome in patients with colorectal cancer lung metastases.

http://dx.doi.org/10.1371/journal.pone.0120724

Stromal Expression of Heat-Shock Protein 27 Is Associated with Worse Clinical Outcome in Patients with Colorectal Cancer Lung Metastases

Abstract

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Public Library of Science (PLOS)

Semmelweis Repository

Repository of the Academy's Library

MedUni Wien ePub

Directory of Open Access Journals