Metallothionein expression in human neoplasia

Histopathology. 2004 Aug;45(2):103-18. doi: 10.1111/j.1365-2559.2004.01922.x.


The metallothionein family is a class of low-molecular-weight, cysteine-rich proteins with high affinity for metal ions. Four major isoforms (metallothionein-1, -2, -3, and -4) have been identified in mammals, involved in many pathophysiological processes, including metal ion homeostasis and detoxification, protection against oxidative damage, cell proliferation and apoptosis, drug and radiotherapy resistance and several aspects of the carcinogenic process. In the present review we examine the expression of metallothionein in different human tumours and its correlation with histopathological variables, tumour cell proliferation or apoptosis, resistance to radiation or chemotherapy, patient survival and prognosis. A variable profile of metallothionein and its isoforms' expression has been observed in different cancer types. Although metallothionein expression has been implicated in carcinogenic evolution, its use as a marker of tumour differentiation, cell proliferation and prognosis predictor remains unclear. Detailed studies focused on the expression of metallothionein isoforms and isotypes in different tumour types could elucidate the role of this group of proteins in the carcinogenic process, delineating its possible clinical significance for the management of patients.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Humans
  • Metallothionein / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Protein Isoforms / metabolism
  • Radiation Tolerance


  • Protein Isoforms
  • Metallothionein