Literature DB >> 11865007

Correlation between cathepsin D expression and p53 protein nuclear accumulation in oesophageal squamous cell carcinoma.

M Ikeguchi1, T Sakatani, T Ueta, K Fukuda, S Oka, K Hisamitsu, K Yamaguchi, S Tsujitani, N Kaibara.   

Abstract

AIM: The lysosomal protease cathepsin D has been reported to be associated with tumour progression in malignant tumours. Expression of the gene encoding cathepsin D is known to be stimulated by oestrogen in mammary cancer cells. Recent experiments revealed that a p53 DNA binding site is located in the promoter region of the cathepsin D gene. This fact indicates that cathepsin D expression may correlate with p53 protein expression. The purpose of this study is to evaluate the expression patterns of the cathepsin D and p53 proteins in oesophageal squamous cell carcinoma (SCC).
METHODS: In 154 patients with oesophageal SCC, expression of the cathepsin D and p53 proteins was measured in tumours by means of immunohistochemistry using monoclonal antibodies against cathepsin D (clone, 1C11) and p53 (clone, BP53-12).
RESULTS: Cathepsin D was detected in tumour cells, although it was not found in normal oesophageal epithelium adjacent to carcinoma. High cathepsin D expression (positive tumour cells > 10%) was detected in 76 of 154 cases (49%) and high p53 nuclear expression (positive tumour cells > 50%) was detected in 70 cases (46%). High cathepsin D expression was significantly associated with invasive tumour growth (p = 0.002), poor prognosis (p = 0.049), and nuclear accumulation of p53 protein (p = 0.001). Overexpression of both p53 and cathepsin D was seen in 45 of the 154 cases (29.2%). In addition, there was a positive correlation between the cathepsin D index (percentage of cathepsin D positive tumour cells) and Ki-67 labelling index (percentage of Ki-67 positive tumour cells) in 154 oesophageal SCCs (rho = 0.257; p = 0.009). However, in multivariate survival analysis, cathepsin D expression by the tumours was not an independent prognostic factor in patients with oesophageal SCC (p = 0.236).
CONCLUSIONS: The expression of cathepsin D by cancer cells may play an important role in the invasive growth of oesophageal SCC. Overexpression of both p53 and cathepsin D was seen frequently in tumours; p53 gene abnormalities may correlate with cathepsin D overexpression in oesophageal SCC.

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Year:  2002        PMID: 11865007      PMCID: PMC1769587          DOI: 10.1136/jcp.55.2.121

Source DB:  PubMed          Journal:  J Clin Pathol        ISSN: 0021-9746            Impact factor:   3.411


  30 in total

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2.  Immunohistochemical detection of cathepsin D in low grade breast invasive cancer.

Authors:  A C Lazaris; G E Theodoropoulos; A K Diamantopoulos; P D Anastassopoulos; P S Davaris
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3.  Immunohistochemical localization of cathepsin D in colorectal tumors.

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4.  Predictive value of c-erbB-2 and cathepsin-D for Greek breast cancer patients using univariate and multivariate analysis.

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Review 5.  Cathepsin D in cancer metastasis: a protease and a ligand.

Authors:  H Rochefort; E Liaudet-Coopman
Journal:  APMIS       Date:  1999-01       Impact factor: 3.205

6.  Variable expression of cathepsin B and D correlates with highly invasive and metastatic phenotype of oral cancer.

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7.  Potential role for cathepsin D in p53-dependent tumor suppression and chemosensitivity.

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8.  Cathepsin B, L, and D activities in colorectal carcinomas: relationship with clinico-pathological parameters.

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9.  Acceleration of proliferative activity of esophageal squamous cell carcinoma with invasion beyond the mucosa: immunohistochemical analysis of Ki-67 and p53 antigen in relation to histopathologic findings.

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10.  Prognostic value of cathepsin D expression and association with histomorphological subtypes in breast cancer.

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Review 2.  Cathepsin D expression levels in nongynecological solid tumors: clinical and therapeutic implications.

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3.  The expression of E-cadherin and cathepsin-D in normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma: A comparative analysis between immunohistochemistry and routine histopathology.

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Review 5.  Cathepsins in digestive cancers.

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Review 6.  Making Connections: p53 and the Cathepsin Proteases as Co-Regulators of Cancer and Apoptosis.

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7.  Cathepsins B, D, and G Are Expressed in Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma.

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8.  Detection of oral squamous cell carcinoma metastasis with cathepsin D: An immunohistochemical approach.

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9.  Overexpression of Lipocalin-2 Inhibits Proliferation and Invasiveness of Human Glioblastoma Multiforme Cells by Activating ERK Targeting Cathepsin D Expression.

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