May Cathepsin D Immunoreactivity Be Used as a Prognostic Factor in Endometrial Carcinomas? A Comparative Immunohistochemical Study
ABSTRACT 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.
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ABSTRACT: Cathepsins B and D belong to a family of proteases involved in tumor invasion and metastasis. As such they may function as biomarkers for the aggressiveness of a given tumor. We examined the enzymatic activity of these proteins as well as the cellular and extracellular distribution of cathepsins B and D. 39 snap frozen tissue samples were assayed for activity fluorometrically with cathepsin-specific peptide substrates in combination with specific inhibitors. 4 groups were established: benign tissue, stage I/grade 1, stage i/grade 3, and stage IIIC/any grade. IHC staining for cathepsin B with the percentage of counterstained enzyme calculated from each specimen. A significantly increased level of cathepsin B activity was seen in malignant tissue specimens when compared to benign tissue. The cathepsin B/D ratio confirmed and was required to detect the significance of this distinction for each malignant group when compared to benign samples. There were no differences in cathepsin B or D expression detected between the various malignant groups. IHC staining for cathepsin B was more diffuse in the malignant tissues. Malignant endometrium displays increased cathepsin B activity when compared benign samples. The cathepsin B/D ratio is increased for each of the malignant groups studied when compared directly to benign endometrium. The cathepsin B/D ratio cannot be utilized to distinguish the stage or grade between any of the malignant groups studied. This ratio may serve to distinguish malignant from benign tumor samples and may be a constitutive change in the malignant transformation.Gynecologic Oncology 02/2008; 108(1):84-9. · 3.93 Impact Factor
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ABSTRACT: Placental leucine aminopeptidase (P-LAP) is a cell surface aminopeptidase (oxytocinase). We cloned P-LAP cDNA and found a widespread tissue distribution of P-LAP. Since P-LAP can degrade several small peptide hormones such as oxytocin, this enzyme may affect many cellular functions of carcinoma cells as well as normal cells. This study investigated whether the expression of P-LAP correlates with clinicopathologic factors and prognosis in patients with endometrial endometrioid adenocarcinoma. Histologic sections of formalin-fixed, paraffin-embedded specimens from 99 primary endometrial carcinomas were stained for P-LAP using polyclonal P-LAP antibody. Disease-free survival and other clinicopathologic characteristics were analyzed according to the intensity of P-LAP staining. Of 99 cases, 69 (69.7%) showed specific P-LAP immunostaining. We found a positive correlation between the expression of P-LAP and histological grade (p < 0.01), surgical stage of the disease (p = 0.02), myometrial invasion (p = 0.01), lymph node involvement (p < 0.01), and vascular infiltration (p < 0.01). In patients who had strongly positive P-LAP staining, the disease-free interval was significantly lower than in patients who had negative or weakly positive P-LAP staining (p < 0.01). Multivariate analysis demonstrated that strongly immunoreactive P-LAP (odds ratio, 12.8; 95% confidence interval, 2.84-58.8; p < 0.01) and surgical stage (odds ratio, 8.78; 95% confidence interval, 2.77-27.8; p < 0.01) are independent prognostic factors. This study suggests P-LAP as an independent prognosticator of clinical outcome in patients with endometrial carcinoma. Therefore, assessment of the P-LAP status provides clinically useful prognostic information in patients with endometrial carcinoma.Oncology 01/2004; 66(4):288-95. · 2.17 Impact Factor
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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.Clinical and Experimental Metastasis 02/2004; 21(2):91-106. · 3.46 Impact Factor