Abstract
Background
The expression of Heat Shock Proteins (HSPs) is increased in various cancers and has been shown to correlate with biological tumor behaviour. This study aimed to investigate the impact of HSP70, HSP60 and HSP27 expression in colon cancer.
Material and methods
HSP expression was determined by immunohistochemistry on a tissue microarray with 355 primary resected colon carcinomas of all stages. Expression patterns were correlated with pathologic features (UICC pTNM category, tumor grading) and survival.
Results
Expression of HSP27, HSP60 and HSP70 ranged from negative to high. There was no correlation between HSP27, HSP60 and HSP70 expression among each other and with UICC pT category, presence of lymph node or distant metastases or tumor grading. High HSP70 expression was associated with worse overall survival (p < 0.001) and was an independent prognostic factor (p = 0.004) in multivariate analysis including the pathological parameters mentioned above. For patients without lymph node or distant metastases (UICC stages I/II) and with complete tumor excision, HSP70 expression was the only independent prognostic factor for survival (p = 0.001) and superior to UICC pT category. In left sided UICC stage I/II carcinomas, high HSP27 expression also had adverse prognostic impact and was an independent prognostic factor (p = 0.016) besides HSP70 (p = 0.002).
Conclusion
High HSP70 and HSP27 expression is associated with worse clinical outcome in colon cancer. Determination of tumoral HSP70 and HSP27 may be used as additional biomarker for risk stratification especially for UICC stage I/II patients.
Similar content being viewed by others
References
J. Ferlay, H.-R. Shin, F. Bray et al., Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer 127, 2893–2917 (2010)
A. Jemal, R. Siegel, E. Ward et al., Cancer statistics, 2009. CA Cancer J. Clin. 59, 225–249 (2009)
D.V.T. Catenacci, M. Kozloff, H.L. Kindler, B. Polite, Personalized Colon Cancer Care in 2010. Semin. Oncol. 38, 284–308 (2011)
L. Sobin, M.L. Gospodarowicz, Ch Wittekind, TNM classification of malignant tumors (John Wiley & Sons, New York, 2010)
M.G. Mutch, Molecular profiling and risk stratification of adenocarcinoma of the colon. J. Surg. Oncol. 96, 693–703 (2007)
S. Tejpar, M. Bertagnolli, F. Bosman et al., Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery. Oncologist 15, 390–404 (2010)
S. Lindquist, E.A. Craig, The heat-shock proteins. Annu. Rev. Genet. 22, 631–677 (1988)
S.K. Calderwood, M.A. Khaleque, D.B. Sawyer, D.R. Ciocca, Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 31, 164–172 (2006)
D.R. Ciocca, S.K. Calderwood, Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10, 86–103 (2005)
A.A. Khalil, N.F. Kabapy, S.F. Deraz, C. Smith, Heat shock proteins in oncology: Diagnostic biomarkers or therapeutic targets? Biochim. Biophys. Acta 1816, 89–104 (2011)
M. Sherman, G. Multhoff, Heat shock proteins in cancer. Ann. N. Y. Acad. Sci. 1113, 192–201 (2007)
F. Cappello, S. David, F. Rappa et al., The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase. BMC Cancer 5, 139 (2005)
T.S. Hwang, H.S. Han, H.K. Choi et al., Differential, stage-dependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer. J. Gastroenterol. Hepatol. 18, 690–700 (2003)
Y. Kanazawa, H. Isomoto, M. Oka et al., Expression of heat shock protein (Hsp) 70 and Hsp 40 in colorectal cancer. Med Oncol 20, 157–164 (2003)
X.P. Wang, G.Z. Liu, A.L. Song et al., Expression and significance of heat shock protein 70 and glucose-regulated protein 94 in human esophageal carcinoma. World J. Gastroenterol. 11, 429–432 (2005)
K. Pfister, J. Radons, R. Busch et al., Patient survival by Hsp70 membrane phenotype: association with different routes of metastasis. Cancer 110, 926–935 (2007)
J. Kocsis, T. Meszaros, B. Madaras et al., High levels of acute phase proteins and soluble 70 kDa heat shock proteins are independent and additive risk factors for mortality in colorectal cancer. Cell Stress Chaperones 16, 49–55 (2011)
A.B. Benson, D. Schrag, M.R. Somerfield et al., American Society of Clinical Oncology Recommendations on Adjuvant Chemotherapy for Stage II Colon Cancer. J. Clin. Oncol. 22, 3408–3419 (2004)
J.L. Marshall, D.G. Haller, A. de Gramont et al., Adjuvant Therapy for Stage II and III Colon Cancer: Consensus Report of the International Society of Gastrointestinal Oncology. Gastrointest Cancer Res 1, 146–154 (2007)
T. Andre, A. de Gramont, An overview of adjuvant systemic chemotherapy for colon cancer. Clin. Colorectal Cancer 4(Suppl 1), S22–S28 (2004)
E.M. Tweedle, I. Khattak, C.W. Ang et al., Low molecular weight heat shock protein HSP27 is a prognostic indicator in rectal cancer but not colon cancer. Gut 59, 1501–1510 (2010)
A. Marx, P. Simon, R. Simon et al., AMACR expression in colorectal cancer is associated with left-sided tumor localization. Virchows Archiv 453, 243–248 (2008)
B. Iacopetta, Are there two sides to colorectal cancer? Int. J. Cancer 101, 403–408 (2002)
R. Langer, K. Ott, K. Specht et al., Protein expression profiling in esophageal adenocarcinoma patients indicates association of heat-shock protein 27 expression and chemotherapy response. Clin. Cancer Res. 14, 8279–8287 (2008)
C.S. Wong, V.W. Wong, C.M. Chan et al., Identification of 5-fluorouracil response proteins in colorectal carcinoma cell line SW480 by two-dimensional electrophoresis and MALDI-TOF mass spectrometry. Oncol Rep 20, 89–98 (2008)
M. Tsuruta, H. Nishibori, H. Hasegawa et al., Heat shock protein 27, a novel regulator of 5-fluorouracil resistance in colon cancer. Oncol Rep 20, 1165–1172 (2008)
D.H. Choi, J.S. Ha, W.H. Lee et al., Heat shock protein 27 is associated with irinotecan resistance in human colorectal cancer cells. FEBS Lett. 581, 1649–1656 (2007)
V. Dudeja, S.M. Vickers, A.K. Saluja, The role of heat shock proteins in gastrointestinal diseases. Gut 58, 1000–1009 (2009)
G. Jego, A. Hazoume, R. Seigneuric, C. Garrido, Targeting heat shock proteins in cancer. Cancer Lett (2010)
Y. Fukuyo, C.R. Hunt, N. Horikoshi, Geldanamycin and its anti-cancer activities. Cancer Lett. 290, 24–35 (2010)
U. Banerji, Heat Shock Protein 90 as a Drug Target: Some Like It Hot. Clin. Cancer Res. 15, 9–14 (2009)
A. Aghdassi, P. Phillips, V. Dudeja et al., Heat shock protein 70 increases tumorigenicity and inhibits apoptosis in pancreatic adenocarcinoma. Cancer Res. 67, 616–625 (2007)
P.A. Phillips, V. Dudeja, J.A. McCarroll et al., Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein 70. Cancer Res. 67, 9407–9416 (2007)
Z.P. Yuan, L.J. Chen, L.Y. Fan et al., Liposomal quercetin efficiently suppresses growth of solid tumors in murine models. Clin. Cancer Res. 12, 3193–3199 (2006)
Acknowledgements
The authors thank Mrs Melitta Winkler for expert technical assistance. This study was supported by the Deutsche Forschungsgemeinschaft (DFG), grant number LA2706/1-1.
Conflict of Interest
The authors declare no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bauer, K., Nitsche, U., Slotta-Huspenina, J. et al. High HSP27 and HSP70 expression levels are independent adverse prognostic factors in primary resected colon cancer. Cell Oncol. 35, 197–205 (2012). https://doi.org/10.1007/s13402-012-0079-3
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13402-012-0079-3