## 4 Discussion  
We found that the number of cells positive for Hsp60 and the positivity of the individual cells in gastric adenocarcinoma (GC) are high compared to the normal mucosa (NM). We also compared GC with other gastric pathologies, as follows: (1) mild-to-moderate gastritis, an inflammatory process without damage or destruction of the glandular structure; (2) severe gastritis, also an inflammatory process but associated with the injury and destruction of the glandular structure; (3) hyperplastic polyp, a paradigm of benign proliferation; (4) intestinal metaplasia, a benign reversible condition for the most part, characterized by morphological variations in the mucosa that probably reflect adaptive changes to a chronic inflammation; and (5) gastric dysplasia, a precancerous condition. The highest levels of Hsp60 positivity were found in GC, but they were also high in gastric dysplasia (GD) in comparison with all the other pathologies studied, which reaffirms the close relationship between GC and GD, with the latter being a prelude to malignant transformation with the atypical alteration of epithelial cells. Additionally, it is of interest that (i) the Hsp60 positivity in hyperplastic polyps (HP) was higher than in normal mucosa (NM) but lower than in GC, even though HP and GC are both characterized by increased cell proliferation; (ii) the Hsp60 positivity was higher in the malignant version of these two examples of increased cell proliferation, HP and GC, but with the difference that GC is undifferentiated and disrupts the tissue structure and infiltrates neighboring spaces, properties not shown by polyps. This indicates that Hsp60 quantitative changes are strongly associated with malignancy (Figure 5). Epithelial cell proliferation in polyps is characterized by an increase in mitotic replication cycles and a reduction in pro-apoptotic stimuli [28; 29] also seen in carcinogenic proliferation, in which genetic mutations may occur [28; 30]. Therefore, both pathologies share tissue remodeling events and factors, including an increase in Hsp60. Previous studies have found that Hsp60 increases in cases of alteration of the transmission of the apoptotic signal [31; 32], and this may occur in the gastric polyps such as those included in this study, in which an altered cell turnover leads to an increase in proliferation. The involvement of Hsp60 in the carcinogenic process also includes its functional participation in many metabolic and biomolecular mechanisms of the cancer cells, encompassing interactions with various other molecules involved in programmed cell death, cell proliferation, and other pathways leading to malignant transformation [31]. Figure 4: (**A**) Representative image of immunohistochemical detection of Hsp60 in gastric mucosa with areas of severe gastritis and areas with glandular dysplasia (magnification 50\(\times\), scale bar 200 \(\upmu\)m). (**B**) Higher magnification of severe gastritis (magnification 200\(\times\), scale bar 50 \(\upmu\)m). (**C**) Higher magnification of gastric dysplasia (magnification 200\(\times\), scale bar 50 \(\upmu\)m). Other authors have also reported an increase in Hsp60 in the process of gastric carcinogenesis [11; 33], ascribing to the chaperonin a fundamental role in the replication mechanisms and in cell survival [33]. Thus, our data are consistent with those from other investigators, showing that the Hsp60 increase is not only associated with the onset of GC but also correlates with the progression of the tumor mass and worsening of the clinical prognosis [11]. Regardless of the mechanisms by which Hsp60 increases in tumor cells, it is likely that the chaperonin aids them and should, therefore, be the target of anti-cancer treatments. The use of compounds to block Hsp60 activity, i.e., negative chaperotherapy, has been proposed and is a promising field for investigation to develop means to defeat not only GC but also various other malignancies [34; 35].