• Corpus ID: 212552325

Stress Proteins HSP 27 and HSP 70 i Predict Survival in Non-small Cell Lung Carcinoma

@inproceedings{Mausecka2008StressPH,
  title={Stress Proteins HSP 27 and HSP 70 i Predict Survival in Non-small Cell Lung Carcinoma},
  author={Ewa Małusecka and Stefania Krzyżowska-Gruca and Jacek Gawrychowski and Anna Fiszer-Kierzkowska and Zofia Kołosza and Zdzisław Krawczyk},
  year={2008}
}

• E. Małusecka, S. Krzyżowska-Gruca, +3 authors Z. Krawczyk
• Published 2008
• Biology, Medicine

Background: The expression pattern of stress (heat shock) proteins (HSPs) in cancer cells is frequently different from that observed in normal cells; most often some stress-inducible HSPs are constitutively and highly expressed. The objective of this study was to determine the prognostic significance of stress proteins HSP70i and HSP27 in non-small cell lung carcinoma (NSCLC). Materials and Methods: An immunohistochemical procedure that enables unambiguous detection of HSP70i protein was used. Results: Strong HSP70i staining showed a survival advantage, although multivariate analysis did not confirm this result. There was an evident correlation between HSP27 overexpression and survival of patients and the results were confirmed by multivariate analysis: 70% of patients with HSP27negative tumors died within one year after the surgery. Conclusion: Our data suggest that HSP27 and HSP70i positivity may represent a favorable prognostic factor in NSCLC. Lung cancer is the leading cause of death from malignant tumors in males and the second in the female population. Although great improvement has been made in diagnosis and treatment of lung cancer, the overall patients' survival is still very low and does not exceed 15% (1). With the advent of adjuvant therapies, it has become increasingly important to discover biomarkers that will identify patients with the highest likelihood of recurrence. A substantial amount of clinical and basic science research has focused on the prognostic factors in lung cancer and a variety of molecular markers have been proposed that may have the potential to predict treatment outcomes. Such markers include cyclin E, cyclin D1, p21, p27, p16 and VEGF (reviewed in (2)). Nonetheless, no single marker has yet been shown to be satisfactory in predicting patient outcome. The heat shock protein (HSP) family, is a group of molecular chaperones, which maintain protein homeostasis under physiological conditions and protect cells against damage in stressful conditions. The expression pattern of HSPs in cancer cells is frequently different from that observed in normal cells: most often some stress-inducible HSPs are constitutively and highly expressed. The accumulation of cytoplasmic HSPs at a physiological temperature in the nuclei or at the cell surface of cancer cells can also be observed (3). The molecular mechanism responsible for overexpression of HSPs encoded by heat shock factor (HSF)-inducible genes such as HSP70i and HSP27 in cancer cells seems to be multiple and has not yet been fully determined. Gene chip microarray studies of prostate cancer cells showed insignificant differences in HSF and HSP gene mRNA expression between the normal and malignant cells, which indicates that HSP expressions might be regulated at the post-transcriptional level in cancer cells (4). Conversely, in pancreatic cancer, HSP70 expression was elevated when compared to normal neighboring tissue from the same patient. There is still the question of whether HSP overexpressions are cancer-causative or if they only reflect increased tumor metabolic activity. From the clinical point of view, stress inducible HSP70i and HSP27 can modulate some processes which are important for tumor development and response to therapy. An elevated level of HSP27 is associated with a diminished cell proliferation rate both in vitro and in vivo, while HSP70i overexpression correlates with increased cell proliferation rate (5,6). Both these proteins hamper apoptosis in many ways (7). This apoptosis-related effect is mainly responsible for the chemoresistance of HSP-overexpressing tumors to commonly used cytostatic drugs (reviewed in (8)). Overexpression of HSP70i also seems to be a factor facilitating aneuploidation of cancer cells (9). 501 Correspondence to: Ewa Malusecka, Department of Tumor Biology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Branch Gliwice 44-101 Gliwice, Poland. Tel: [phone], Fax: [phone], e-mail: [e-mail]