Determination of p185 and adenylosuccinate lyase (ASL) activity in preneoplastic colon lesions and intestinal mucosa of human subjects.

OBJECTIVES: The HER2 gene has been found amplified in a number of human adenocarcinoma leading to elevated levels of expression of its encoded product, p185 protein. Because little information is available on the tissue and tumor specificity of this gene product, we studied the expression of p185 protein in preneoplastic colon lesions. Adenylosuccinate lyase (ASL, EC 4.3.2.2) is known to increase in malignancies such as colorectal, breast, and prostate cancer. In order to evaluate the potential of ASL as a tumor marker, its activity was determined and compared with the expression of p185. DESIGN AND METHODS: p185 was determined by an immunohistochemical procedure in patients with the preneoplastic lesions. ASL activity was evaluated in intestinal mucosa adjacent to colorectal cancers (patient group A) and in preneoplastic colorectal lesions (group B). The enzyme activity was evaluated in dialyzed supernatants, following the disappearance of substrate (adenylosuccinate AMP-S) and the formation of product (adenosine 5'-monophosphate-AMP), separated by high performance liquid chromatography. RESULTS AND
CONCLUSIONS: Increased expression of p185 and elevated ASL activity were observed in tubular and tubulo-villous adenoma and may, therefore, be associated with the early stages of colorectal cancer.