Differential expression of the nm23 protein in the progression of oesophageal adenocarcinoma

Abstract

Aim Some studies have shown that abnormalities of the nm23 gene or its expression may be important in tumour dissemination, suggesting that the gene may have metastasis suppressing activity. This study set out to determine if nm23 protein expression is altered with progression and dissemination in oesophageal adenocarcinoma. Methods Paraffin-embedded, archival tissues of surgical resection specimens of oesophageal adenocarcinoma (n = 46), some of which were accompanied by tissue from areas with high-grade dysplasia (n = 24) and from metastasis in regional lymph nodes (n = 16) were studied. Histologically normal oesophageal glandular tissue (of cardiac-type) (n = 32) obtained from areas of the resections located away from the primary tumour masses and archival tissues of Barrett's metaplasia obtained from endoscopic biopsies (n = 77) were used as non-neoplastic controls. Sections were immuno-histochemically stained by the labelled streptavidin-biotin method using NCL-nm23 antibody. Results The total or overall amount of nm23 protein expression paralleled that of cytoplasmic expression and was increased in oesophageal adenocarcinomas (36/46 cases, 78%) when compared with normal oesophageal glandular epithelium (2/32, 6%), Barrett's metaplasia (8/77, 10%) and dysplasia (14/24, 58%). In metastatic carcinoma in regional lymph nodes, overall nm23 expression was similar in proportion (13/16, 81%) to that seen in primary carcinoma. In the analysis of the sequential development of oesophageal adenocarcinoma based on non-neoplastic, preneoplastic and neoplastic archival material, it was found that a high level of overall nm23 expression occurred firstly at the transition from Barrett's metaplasia (8/77, 10%) to dysplasia (14/24, 58%). Nuclear nm23 expression was low in dysplastic tissue (with none of the cases having a high level of nuclear nm23 expression) followed by increased levels as the lesion progressed to invasive adenocarcinoma (13/46, 28%) and metastatic carcinoma in regional lymph nodes (10/16, 63%). However, nm23 expression did not appear to correlate with sex, age, tumour size, extent of tumour infiltration into the oesophageal wall, presence of lymph node metastasis or overall patient survival. Conclusion An overall increase in nm23 expression or increase in nm23 expression in the cytoplasm of cells may be important in the early development of oesophageal adenocarcinoma but increased levels of nuclear nm23 occur in its progression to metastatic disease. Some studies have shown that abnormalities of the nm23 gene or its expression may be important in tumour dissemination, suggesting that the gene may have metastasis suppressing activity. This study set out to determine if nm23 protein expression is altered with progression and dissemination in oesophageal adenocarcinoma. Paraffin-embedded, archival tissues of surgical resection specimens of oesophageal adenocarcinoma (n = 46), some of which were accompanied by tissue from areas with high-grade dysplasia (n = 24) and from metastasis in regional lymph nodes (n = 16) were studied. Histologically normal oesophageal glandular tissue (of cardiac-type) (n = 32) obtained from areas of the resections located away from the primary tumour masses and archival tissues of Barrett's metaplasia obtained from endoscopic biopsies (n = 77) were used as non-neoplastic controls. Sections were immuno-histochemically stained by the labelled streptavidin-biotin method using NCL-nm23 antibody. The total or overall amount of nm23 protein expression paralleled that of cytoplasmic expression and was increased in oesophageal adenocarcinomas (36/46 cases, 78%) when compared with normal oesophageal glandular epithelium (2/32, 6%), Barrett's metaplasia (8/77, 10%) and dysplasia (14/24, 58%). In metastatic carcinoma in regional lymph nodes, overall nm23 expression was similar in proportion (13/16, 81%) to that seen in primary carcinoma. In the analysis of the sequential development of oesophageal adenocarcinoma based on non-neoplastic, preneoplastic and neoplastic archival material, it was found that a high level of overall nm23 expression occurred firstly at the transition from Barrett's metaplasia (8/77, 10%) to dysplasia (14/24, 58%). Nuclear nm23 expression was low in dysplastic tissue (with none of the cases having a high level of nuclear nm23 expression) followed by increased levels as the lesion progressed to invasive adenocarcinoma (13/46, 28%) and metastatic carcinoma in regional lymph nodes (10/16, 63%). However, nm23 expression did not appear to correlate with sex, age, tumour size, extent of tumour infiltration into the oesophageal wall, presence of lymph node metastasis or overall patient survival. An overall increase in nm23 expression or increase in nm23 expression in the cytoplasm of cells may be important in the early development of oesophageal adenocarcinoma but increased levels of nuclear nm23 occur in its progression to metastatic disease.