PURPOSE: To evaluate the prognostic significances of p53 and cathepsin D in the prostatic carcinoma, we compared them to other prognostic factors, such as nuclear grade and clinical stage. MATERIALS AND METHODS: The material consisted of 40 paraffin-embedded, primary prostate carcinomas. We examined the expression of p53 and cathepsin D using immunohistochemical staining and compared their expression with the grade and stage. RESULTS: The expressions of p53 were noted in the nucleus of tumor cells and cathepsin D were noted in the cytoplasm of tumor cells. Thirteen of 40 tumors were positive for p53. There were more expressing p53 in samples (40%) from prostatic cancer with a high Gleason score group than in samples (28%) from prostatic cancer with low Gleason score group. The expression of p53 was 22% in clinical stage B and C groups and 35% in clinical stage D group. These results showed that p53 expression was not statistically correlated with Gleason score and clinical stage, but there were trends to increased p53 expression with high Gleason score and progressed clinical stage (p>0.05). Progressed clinical stage group showed higher expression of cathepsin D than early clinical stage group. However, there were no statistical correlations between expression of cathepsin D and Gleason score, and clinical stage (p>0.05). CONCLUSION: These results suggest that the overexpression of p53 and cathepsin D may be associated with tumor differentiation and clinical stage, but have limited prognostic value in prostatic carcinoma.
Cathepsin D* ; Cathepsins* ; Cytoplasm ; Neoplasm Grading ; Prostate ; Prostatic Neoplasms

Twenty six cases of primary adenocarcinoma of the prostate, ranging from 4 to 9 according to Gleason's summing score, were studied. Immunoreactivity was evaluated using the rabbit polyclonal anti-Cathepsin D antibody (CD), a mouse monoclonal MMP-2 antibody (MMP-2), and a tissue inhibitor metalloproteinase (TIMP) in formalin-fixed, paraffin-embedded prostatic tissue. Immunohistochemical staining was scored by summing the intensity of staining (0 to 3+) weighted by the percentage of tumor staining at each intensity (H score, theoretical range 0 to 300). For CD, the tumor cells showed diffuse cytoplasmic immunoreactivity in all 26 cases (100%). For MMP-2 the tumor cells showed cytoplasmic immunoreactivity in 17 of 26 cases (65.38%). As the Gleason grade increased the expression of CD increased (P=0.0027). The reactivity of CD was significantly correlated with the Gleason's score (R=0.65637), but, the reactivity of MMP-2 was not correlated. There were no significant correlations between each of the CD and the MMP-2 scores, and stage. TIMP expression was predominantly localized in the stroma rather than in the cancer cells themselves. We believe that 1) CD and MMP-2, both immunohistochemically detectable in a majority of prostate adenocarcinoma, may play a role in determination of the invasive or metastatic property, 2) the enhanced TIMP expression in the stroma may be associated with the response to cancer invasion.
Adenocarcinoma ; Animals ; Cathepsin D* ; Cathepsins* ; Cytoplasm ; Mice ; Prostate*

PURPOSE: The purpose of this study was to find out what clinicopathologic or immunohistochemical parameter that may affect FDG uptake of primary tumor in PET/CT scan of the gastric carcinoma patient. MATERIALS AND METHODS: Eighty-nine patients with stomach cancer who underwent pre-operative FDG PET/CT scans were included. In cases with perceptible FDG uptake in primary tumor, the maximum standardized uptake value (SUVmax) was calculated. The clinicopathologic results such as depth of invasion (T stage), tumor size, lymph node metastasis, tumor differentiation and Lauren's classification and immunohistochemical markers such as Ki-67 index, expression of p53, EGFR, Cathepsin D, c-erb-B2 and COX-2 were reviewed. RESULTS: Nineteen out of 89 gastric carcinomas showed imperceptible FDG uptake on PET/CT images. In cases with perceptible FDG uptake in primary tumor, SUVmax was significantly higher in T2, T3 and T4 tumors than T1 tumors (5.8+/-3.1 vs. 3.7+/-2.1, p=0.002). SUVmax of large tumors (above or equal to 3 cm) was also significantly higher than SUVmax of small ones (less than 3 cm) (5.7+/-3.2 vs. 3.7+/-2.0, p=0.002). The intestinal types of gastric carcinomas according to Lauren showed higher FDG uptake compared to the non-intestinal types (5.4+/-2.8 vs. 3.7+/-1.3, p=0.003). SUVmax between p53 positive group and negative group was significantly different (6.0+/-2.8 vs. 4.4+/-3.0, p=0.035). No significant difference was found in presence of LN metastasis, tumor differentiation, Ki-67 index, and expression of EGFR, Cathepsin D, c-erb-B2 and COX-2. CONCLUSION: T stage of gastric carcinoma influenced the detectability of gastric cancer on FDG PET/CT scan. When gastric carcinoma was perceptible on PET/CT scan, T stage, size of primary tumor, Lauren's classification and p53 expression were related to degree of FDG uptake in primary tumor.
Cathepsin D ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Stomach Neoplasms

Adenocarcinoma, Mucinous ; enzymology ; pathology ; Cathepsin B ; metabolism ; Cathepsin D ; metabolism ; Colorectal Neoplasms ; enzymology ; pathology ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness

No abstract available.
Cathepsin D* ; Cathepsins* ; Cell Cycle* ; Flow Cytometry ; Immunohistochemistry ; Proliferating Cell Nuclear Antigen*

BACKGROUND: It is known that cathepsin D expression in host stromal cells is associated with a more aggressive tumor behavior in breast cancers. METHODS: Cathepsin D expression was examined in 222 cases of invasive ductal carcinoma (CA) and 25 cases of ductal carcinoma in situ (DCIS) by the immunohistochemical staining. Cathepsin D expression was evaluated according to the expression site, either in the tumor cells (CD-T) or in the stromal cells (CD-S), and graded according to the immunopositivity. The differences of CD-T and CD-S in each case were evaluated according to the pathologic parameters and estrogen receptor (ER)/progesterone receptor (PR) status. RESULTS: The rate of CD-S was significantly higher in the CA than in the DCIS (p<0.0001). In the CA, the rate of CD-S was higher than that of CD-T, while in the DCIS, the rate of CD-T was higher than that of CD-S. In the CA, the rate of CD-S and the tumor grade showed a positive relationship (p=0.0281). There were positive correlations between the ER positivity and CD-S (p=0.0236), and between the PR positivity and CD-T (p=0.0246). For the DCIS, no significant relationships were noted between the pathologic parameters including ER/PR status and CD-T/CD-S. CONCLUSION: Cathepsin D expression in the stromal cells seems to be related to the invasiveness and aggressive biological behavior in breast cancers. In addition, there might be some relationship betweeen the ER positivity and CD-S, and between the PR positivity and CD-T.
Breast Neoplasms ; Breast* ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating* ; Cathepsin D* ; Cathepsins* ; Estrogens ; Stromal Cells

BACKGROUND: To investigate the molecular basis for invasion of malignant gliomas, proteomic analysis approach was carried out using two human glioma cell lines, U87MG and U343MG-A that demonstrate different motility and invasiveness in in vitro experiments. METHODS: High-resolution two-dimensional gel electrophoresis and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry analysis were performed. RESULTS: Nine distinct protein spots that were recognized with significant alteration between the two cell lines. Five of these protein spots were up-regulated in U87MG and four were up-regulated in U343MG-A. CONCLUSION: Among these proteins, cathepsin D was shown to be one of the important proteins which are related with glioma invasion. However, further studies are necessary to reveal the exact role and mechanism of cathepsin D in glioma invasion.
Cathepsin D ; Cell Line* ; Electrophoresis, Gel, Two-Dimensional ; Glioma* ; Humans ; Mass Spectrometry ; Proteomics

PURPOSE: Ductal carcinoma in situ (DCIS) of the breasts is a heterogeneous group of lesions with diverse malignant potentials and controversial treatment options. This study was planned to investigate the patterns of clinicopathologic parameters and tumor markers related to biological aggressiveness and to make treatment decisions available based on a variety of these parameters. METHODS: We reviewed forty cases of DCIS treated at Pusan Paik Hospital from March 1992 to July 2002. Clinicopathologic features such as age, chief complaint, mammographic finding, tumor size, histologic subtype, and operation type were analysed, and the expression of ER, PR, p53, C- erbB-2, cathepsin D, bcl-2, MIB-1 and CD34 were evaluated using immunohistochemical methods. RESULTS: The size of the tumor was less than 1.5 cm in 16 (44.4%) cases, 1.5 cm to 4 cm in 17 (47.2%) cases, and more than 4 cm in 3 (8.3%) cases. There were 11 (27.5%) cases of the comedo subtype and 29 (72.5%) cases of the noncomedo subtype. Nuclear grade was divided into low (8 cases, 20.0%), intermediate (20 cases, 50.0%), and high (12 cases, 30.0%). According to Van Nuys' classification, there were 25 (62.5%) cases, 4 (10.0%) cases, and 11 (27.5%) cases of group I, II, and III, respectively. The groups presenting as mass on mammogram had no significant relationship with those presenting as microcalcification in terms of tumor size, histologic subtype, nuclear grade, and Van Nuys classification. The expression rates of PR, p53, C-erbB-2, cathepsin D, and bcl-2 were 32.4%, 67.6%, 35.1%, 29.7%, 67.6%, and 45.9%, respectively. High MIB-1 labelling index (LI) and high microvessel density were observed in 8.1% and 32.4%, respectively. The group presenting as mass on mammogram showed higher ER (P=0.0276) and PR (P=0.102) expression, compared with the microcalcification group. Positive ER and PR were associated with low nuclear grade (P=0.0233, 0.1727), while positive p53 and C-erbB-2 and high MIB-1 LI correlated with Van Nuys' group III (P=0.0637, 0.0532). Positive ER correlated with positive PR (P=0.0581) and negative C-erbB-2 (P=0.0642). In addition, there were positive associations between PR and bcl-2 expression (P=0.0939), between p53, C-erbB-2 (P<0.0001) and high MIB-1 labelling index (P= 0.0785), and between cathepsin D and high microvessel density (P= 0.0151). CONCLUSION: Clinico-pathologic evaluation of tumor size, histologic subtype, nuclear grade, and Van Nuys classification can help predict more aggressive immunophenotypes of DCIS. Positive p53 and C-erbB-2 and high MIB-1 is associated not only with more aggressive clinical behavior and more advanced histologic features of DCIS, but also with negative ER, PR, and bcl-2. Our results support the clinical relevance of combining both clinico-pathologic factors and biologic tumor markers for determining the treatment modality in DCIS patients.
Biomarkers, Tumor* ; Breast* ; Busan ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating ; Cathepsin D ; Classification ; Humans ; Microvessels

This study was conducted to assess the prognostic value of tumor angiogenesis and Cathepsin-D in breast carcinoma, by correlating them with other clinicopathologic prognostic factors. In order to estimate microvessels within the tumor, an immunohistochemical method using monoclonal antibodies for factor VIII-related antigens (DAKO-vWf, F8/86) was used, and they were counted (perx200 field) in the most active areas of neovascularization. For the expression of Cathepsin-D, an immunohistochemical method using monoclonal antibodies (Novocastra, NCL-CDm) was performed. The microvessel count ranged from 8 to 346 per x200 field and the mean (+/-SD) was 72.46+/-54.96. The microvessel count was correlated with the estrogen receptor status, and it was also correlated with the tumor size when it was graded into four groups (1-33, 34-67, 68-100, >100), but was not correlated with other clinicopathologic parameters. Cathepsin-D was expressed in 40% (46/115) of the cases, but it was statistically correlated with the tumor size only. In conclusion, the expression of Cathepsin D and the degree of angiogenesis in breast cancer showed a correlation with the tumor size only. Therefore, they do not appear to be good prognostic parameters, according to the present study.
Antibodies, Monoclonal ; Breast Neoplasms ; Breast* ; Carcinoma, Ductal* ; Cathepsin D ; Estrogens ; Microvessels ; Prognosis ; von Willebrand Factor

PURPOSE: Cathepsin D, a lysosomal protease has been proposed to play a role in the local invasion and metastatic dissemination in primary breast cancer. Although there are many conflicting results, the overexpression of cathepsin D has been considered to be related with a poorer prognosis of breast cancer. This study was designed to verify whether cathepsin D expression is related to other prognostic factors in breast cancer. METHODS: Cathepsin D was assessed by immunohistochemistry using murine monoclonal anti-cathepsin D antibody (ZyMED) in 79 paraffin-embedded primary breast cancer specimens. Cathepsin D expression was compared to other prognostic parameters such as tumor size, axillary lymph node metastasis, tumor histologic grades, hormone receptors (ER & PR), p53, c-erb B2, Ki-67, MVD (microvessel density), and Pgp (P-glycoprotein). RESULTS: A high-expression of cathepsin D was found in 35 of 79 patients (44.3%) with primary breast cancer. Cathepsin D expression was not related to tumor size, axillary lymph node metastasis, tumor histologic grades, hormone receptors, p53, Ki-67, or CD31. However, a significant relationship was found between cathepsin D expression and c-erb B2 (p=0.007), and between cathepsin D expression and Pgp (p=0.003). CONCLUSION: These results suggest that cathepsin D expression may be an indicator of a poor prognosis in breast cancer. However, further studies are required to verify the xact role of cathepsin D in the prognosis of breast cancer.
Breast Neoplasms* ; Breast* ; Cathepsin D* ; Cathepsins* ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis