May Cathepsin D Immunoreactivity Be Used as a Prognostic Factor in Endometrial Carcinomas? A Comparative Immunohistochemical Study
Objective: To investigate the prognostic value of immunohistochemical detection of cathepsin D and the association between cathepsin D and established prognostic factors in endometrial carcinoma. Methods: Cathepsin D immunoreactivity was determined by an immunohistochemical technique in a series of 79 patients with surgical stage I-III primary endometrial carcinoma. Results: Of 79 tissue specimens, 48 (61%) showed a positive reaction for cathepsin D. A significant correlation between cathepsin D and histological grade was found (P < 0.05). The other established clinicopathological prognostic factors were not associated with cathepsin D. There was not any significant difference in prognosis between the positive cases and negative cases for cathepsin D (P > 0.05). In the univariate analysis cathepsin D immunoreactivity did not show significant prognostic value for overall survival (P > 0.05). The multivariate analysis also showed that cathepsin D was not related to patient outcome (P = 0.24, relative risk = 0.34, 95% confidence interval = 0.05-2.09). Conclusions: Our results suggest that cathepsin D immunoreactivity may not be of prognostic value but more studies are needed to evaluate the relationship between its immunoreactivity in tumor cells and in other cells.
[Show abstract] [Hide abstract] ABSTRACT: Cathepsin D is a lysosomal acid proteinase which is involved in the malignant progression of breast cancer and other gynecological tumors. Clinical investigations have shown that in breast cancer patients cathepsin D overexpression was significantly correlated with a shorter free-time disease and overall survival, whereas in patients with ovarian or endometrial cancer this phenomenon was associated with tumor aggressiveness and a degree of chemoresistance to various antitumor drugs such as anthracyclines, cis-platinum and vinca alkaloids. Therefore, a lot of research has been undertaken to evaluate the role and the prognostic value of cathepsin D also in other solid neoplasms. However, conflicting results have been generated from these studies. The discrepancies in these results may, in part, be explained with the different methodological approaches used in order to determine the levels of expression of the enzyme in tumor tissues and body fluids. Further investigations using well-standardized techniques may better define the clinical significance of cathepsin D expression in solid tumors. Nevertheless, evidence emerging from these studied indicates that this proteinase seems to facilitate early phases of tumor progression such as cell proliferation and local dissemination. These findings support the concept that cathepsin D may be a useful marker for identifying patients with highly malignant tumor phenotypes who may need more aggressive clinical treatment; this enzyme may also be considered as a potential target for a novel therapeutic approach in the treatment of solid neoplasms.0Comments 67Citations
- "Conflicting results were also obtained in other gynecological malignancies [42– 54]. However, these investigations additionally highlighted a close association between altered expression levels of CD and the degree of aggressiveness and chemoresistance of ovarian or endometrial tumors4243444546474849505152535455 . In this context, several investigations have also been undertaken to assess the clinical significance of CD expression in other nongynecological solid tumors. "
- [Show abstract] [Hide abstract] ABSTRACT: Cathepsin D (CathD), a lysosomal aspartyl protease secreted by normal and malignant cells, is considered to be involved in breakdown of the extracellular matrix. Aim of the present study was to determine the frequency and tissue distribution of CathD in normal, hyperplastic and malignant endometrium. Paraffin-fixed endometrial tissue was obtained from premenopausal women in the proliferative phase (n = 5), early secretory phase (n = 4) and late secretory phase (n = 4) as well as glandular-cystic hyperplasia (n = 5), endometrial polyps (n = 5), endometrial polyps from the use of tamoxifen (n = 5), adenomatous hyperplasia (AH) grade I (n = 5), grade II (n = 4), grade III (n = 5) and endometroid adenocarcinoma (n = 5). CathD expression was evaluated with the IRS score and ANOVA analysis was used for statistical evaluation. CathD was primarily localised in luminal and glandular epihelium with little staining in stromal cells. The expression of CathD was significantly higher during the late secretory phase than in the proliferative phase. Highest expression of CathD was observed in the late secretory phase and in glandular-cystic hyperplasia, whereas endometroid carcinoma showed no expression. A continuous increase in CathD expression was observed in AH, with a significant difference between AH grade I and III. In conclusion, CathD was found to be expressed in normal and hyperplastic endometrial tissue. CathD immunostaining in normal endometrial glands varied on the basis of the phase of the menstrual cycle, suggesting physiological functions of CathD in endometrial maturation and degradation. Adenocarcinomas did express significant lower amounts of CathD. Therefore, the prognostic value of this parameter remains uncertain. A continuous increase in CathD immunostaining was observed in AH. Since AH grade III can be considered as a precursor of endometrial cancer, CathD could be a possible parameter for assessing malignant transformation.0Comments 41Citations
- [Show abstract] [Hide abstract] ABSTRACT: Cathepsin D is an aspartyl proteinase involved in tumoral invasion. The aim of this work was to study cathepsin D cytosolic levels in squamous carcinomas of the lung and their correlation with several clinical and biological parameters. The study group included 95 squamous lung carcinomas and 38 normal tissue samples from the same patients. Cathepsin D cytosolic concentrations were determined using an immunoradiometric assay (CIS BioInternational. France). EGFR, erbB2 protein, CD44s, CD44v5 and CD44v6 levels at cell surfaces were determined. The clinical stage, histological grade, ploidy and S-phase cellular fraction (SP) were also considered as variables of the study. Cathepsin D cytosolic levels oscillated between 7.7 and 576 (median: 38.8) pmol/mg protein and were lower (p = 0.001) than those observed in 38 normal lung samples from the same patients. When tumors were classified according to different clinical and biological parameters, we noticed that cathepsin D levels were higher in carcinomas with lower proliferation rates and no nodal involvement, reaching statistical significance in both cases. Moreover, when lung carcinomas were classified according to cathepsin D concentrations, tumors with higher cathepsin D concentrations had lower EGFR levels (p = 0.011) and small global SP values (p = 0.025) and DNA index (p = 0.023). Likewise, they were found to be CD44s positive more frequently (p = 0.001) and SP positive less frequently (p = 0.022). These results lead us to suggest the following: a) in squamous carcinomas of the lung, cathepsin D cytosolic levels are lower than those observed in normal lung samples from the same patients, and b) in this subtype of lung carcinomas, high cathepsin D levels are associated with tumors without nodal involvement, with low proliferation rates, lower EGFR levels, and a reduced positivity for CD44s, pointing to a possible role of this proteinase as a parameter of good outcome.0Comments 5Citations