Prognostic significance of metallothionein in human gastrointestinal cancer.
OBJECTIVE
Metallothionein (MT) is a small protein with a high affinity for divalent heavy metal ions. This metalloproteinis involved in many (patho)physiological processes, like metal homeostasis and detoxification, cell proliferation, apoptosis, therapy resistance, and protection against oxidative damage. Alterations in the immunohistochemical expression of MT have been reported for various human tumors, and a high expression has been found to be associated with a poor clinical outcome. We showed previously that gastrointestinal cancer is accompanied by a decrease in MT expression, but the most malignant phenotypes had the highest MT levels. The purpose of the present study was to assess the clinical relevance of MT in gastrointestinal cancer.


METHODS
In this study, we determined the MT levels, by radioimmunoassay, in intestinal tissue of 251 patients with colorectal cancer and 81 patients with gastric cancer and assessed the relation with the overall survival of these patients.


RESULTS
More than 74% of the carcinomas were found to have a lower MT level than their corresponding normal mucosa. In colorectal cancer patients, but not in gastric cancer patients, a high MT level in both the carcinomas and normal mucosa was, however, significantly associated with a poor overall survival, independently from clinicopathological features.


CONCLUSIONS
Overexpression of MT in intestinal tissue of colorectal cancer patients is a prognostic marker for a poor overall survival. In gastric cancer, however, MT expression in the gastric mucosa is not of prognostic significance. This observation emphasizes the clinical relevance of this multifunctional metalloprotein in colorectal carcinogenesis and therapy.
Janssen
A Miranda L
AM
Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
van Duijn
Wim
W
Kubben
Frank J G M
FJ
Griffioen
Gerrit
G
Lamers
Cornelis B H W
CB
van Krieken
Johan H J M
JH
van de Velde
Cornelis J H
CJ
Verspaget
Hein W
HW
D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D011863:Radioimmunoassay; D015996:Survival Rate
D008668:Metallothionein