ORIGINAL ARTICLE

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

M Ikeguchi¹, T Sakatani², T Ueta³, K Fukuda¹, S Oka¹, K Hisamitsu¹, K Yamaguchi¹, S Tsujitani¹, N Kaibara¹

¹ Department of Surgery I, Faculty of Medicine, Tottori University, 36–1 Nishi-cho, Yonago 683–8504, Japan
² Department of Pathology I, Faculty of Medicine, Tottori University, Nishi-cho 86–1, Yonago 683–8503, Japan
³ Department of Pathology II, Faculty of Medicine, Tottori University, Nishi-cho 86–1, Yonago 683–8503, Japan

Correspondence to:
Correspondence to:
Dr M Ikeguchi, Department of Surgery I, Faculty of Medicine, Tottori University, 36–1 Nishi-cho, Yonago 683–8504, Japan;
surgery1{at}grape.med.tottori-u.ac.jp

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 ( = 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.

Keywords: cathepsin D; oesophageal squamous cell carcinoma; immunohistochemistry; p53 protein accumulation

Abbreviations: CD, cathepsin D; CI, confidence interval; HR, hazards ratio; LI, labelling index; PBS, phosphate buffered saline; SCC, squamous cell carcinoma

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?