IMMUNOHISTOCHEMICAL METALLOTHIONEIN EXPRESSION IN COLORECTAL ADENOCARCINOMA - CORRELATION WITH TUMOR STAGE AND PATIENT SURVIVAL

Metallothioneins (MTs), a set of ubiquitous low-molecular-weight prote ins essential for the protection of cells against heavy metal ion toxi city, were demonstrated immunohistochemically using a monoclonal antib ody (E9) against a conserved epitope of I and II isoforms in a series of 109 colorectal adenocarcinomas. In a semiquantitative analysis stro ng MT expression in the majority of tumour cells was observed in 34 (3 1%) cases, 24 (22%) tumours showed a focal MT positivity, and 51 (47%) almost completely lacked MT expression. These differences in MT expre ssion were statistically significantly (P<0.05) associated with the tu mour stage (Dukes classification) and the lymph node involvement at th e time of operation (pN stages). However, in contrast to previous find ings obtained on a variety of tumours, MT positivity was associated wi th a favourable clinical outcome in colonic carcinoma, which may indic ate their different biological behaviour. Survival curves of cases wit h MT-positive and MT-negative status differed from each other in a uni variate analysis (Mantel-Haenszel 8.9, P<0.05) but lost significance w hen a multivariate analysis was carried out by means of the Cox propor tional regression model with Dukes' stages as a stratification factor. It is concluded that immunohistochemically demonstrated MT expression is significantly associated with tumour stages but does not represent an independent prognostic variable in colorectal cancer. However, it may provide important information about some of the biological mechani sms underlying progression in colorectal cancer.