Cancer Letters

Cancer Letters

Volume 178, Issue 1, 8 April 2002, Pages 99-106
Cancer Letters

Significant correlation between expression of heat shock proteins 27, 70 and lymphocyte infiltration in esophageal squamous cell carcinoma

https://doi.org/10.1016/S0304-3835(01)00825-4Get rights and content

Abstract

The objective of this study was to clarify the clinicopathologic and prognostic significance of heat shock proteins (HSP) 27 and 70 expression in esophageal squamous cell carcinoma (SCC). Immunohistochemical staining for HSPs 27 and 70 was performed on surgical specimens obtained from 62 patients with esophageal SCC. The expression of both HSPs 27 and 70 correlated inversely with depth of invasion (P<0.05) and pathologic stage (P<0.05), and correlated positively with lymphocyte infiltration (P<0.05). Reduction of HSP 70 expression was significantly correlated with poor prognosis (P<0.05). Patients with HSP 27-negative tumors tended to have a poor prognosis compared with patients with HSP 27-positive tumors. The present findings suggest that HSPs 27 and 70 are significant prognostic factors for esophageal SCC.

Introduction

Heat shock proteins (HSPs) are a set of highly evolutionarily conserved proteins found in nearly all organisms. They are known to be induced by various kinds of stress, including exposure to non-physiologic temperatures. However, recent studies have demonstrated that several HSPs are expressed even under physiologic conditions and that they play important roles in specific functions of the cell [1]. Expression levels of HSPs have been reported to be altered, either increasing or decreasing, during carcinogenesis [2], [3]. Among the families of HSPs, HSPs 27 and 70 have been shown to have a strong association with various carcinomas [4], [5], [6], [7], [8], [9], [10].

Although HSP expression has been recognized as a factor of prognostic value in certain tumors, the data are limited and the results are often contradictory. For example, with regard to breast carcinoma, some investigators have reported that HSP 27 expression is an indicator of poor prognosis [5], [6], whereas others have reported that it is an indicator of good prognosis [7]. With respect to HSP 70, expression in colorectal carcinoma and breast carcinoma was significantly correlated with low differentiation and poor prognosis [8], [9], whereas in renal cell carcinoma it was reported to be associated with good prognosis [10]. Thus, the clinical significance of HSPs has not been elucidated and remains controversial.

Although several studies have been performed to elucidate the relationship between HSPs and tumors in various organs, to our knowledge there is only a single report related to esophageal carcinoma. The expression of HSPs 27 and 70 correlated negatively with lymph node metastasis, and indicated a good prognosis [4]. But the relationship between the expression of HSPs and host immunity has not been serially analyzed previously. In this study, to clarify whether these HSPs can be considered as significant prognostic factors, we examined immunohistochemically the relationship between expression of HSPs 27 and 70, pathologic tumor variables and prognosis in patients with esophageal squamous cell carcinoma (SCC), and lymphocyte infiltration was also examined as a marker of host immunity.

In addition, HSP 70 is thought to be associated with carcinogenesis because it forms a complex with mutant p53 protein, for example in breast cancer in vitro and in vivo [11], which is overexpressed when there is a mutation in the tumor suppressor p53 gene [12], [13], [14], [15], [16], [17]. Therefore, immunohistochemical expression of p53 protein was also examined in this series.

Section snippets

Patients

Surgical specimens were obtained from 62 patients (53 males and 9 females) who had esophageal SCC and underwent potentially curative surgery at the Department of Surgery I, Gunma University Faculty of Medicine, between 1983 and 2000. The age of the patients ranged from 41 to 78 years with a mean age of 61.3 years. Tumor stage and disease grade were classified according to the fifth edition of the TNM classification of the International Union Against Cancer (UICC). None of the patients had

Immunohistochemistry of HSPs 27 and 70

Immunoreactivity for HSP 27 was strongly positive in normal stratified squamous epithelium of the esophagus (Fig. 1A), and was localized in the cytoplasm. Several staining patterns were observed for the expression of HSP 27 in tumor tissues. Some tumors showed a diffuse decrease in HSP 27 expression, and others had both positive and negative cell colonies (Fig. 1B). Although the expression pattern of HSP 70 was almost identical to that of HSPs 27, 70 was detected in the nuclei of some tumor

Discussion

In this study, immunohistochemical examination of HSPs 27 and 70 revealed strong expression of HSPs 27 and 70 in normal esophageal squamous epithelium, but frequent partial loss of expression in tumor cells. Normal esophageal squamous epithelia are frequently exposed to agents such as heat or chemicals, so HSPs may be expressed continually and play an important role in protecting cells [19].

Although the mechanism responsible for alteration of HSP expression in tumor cells is unknown, there may

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