Tissue ferritin concentration in carcinoma of the breast

Abstract

Ferritin concentration was measured in cytosol extracts of 44 mammary carcinomas and 14 benign breast tissues. A six‐fold difference was observed (mean, 364.6 ± 223.3 ng/mcp in malignant tissue versus mean, 60.2 ± 42.1 ng/mcp in benign tissue P < 0.001). Thirty‐five malignant tissue specimens were reviewed independently by a pathologist without knowledge of their ferritin contents. Higher concentrations of ferritin were present in malignancies with greater degrees of epithelial proliferation and plemorphism suggesting the malignant epithelium as the major site of the increased ferritin. There was no correlation between desmoplastic reaction within the tumors or inflammation within or adjacent to the tumors and ferritin concentration. Ferritin in breast tissue may be important as a marker of neoplasia, a source of elevated serum ferritin, an indicator of clinical prognosis or an immunosuppressive substance.

Regulation of ferritin genes and protein

“…174 However, subsequent evaluations of ferritin levels in tumor tissue itself have revealed a complex, perhaps disease-specific picture: for example, in some cases such as colon cancer, 175 testicular seminoma, 176 and breast cancer, 177,178 increases in ferritin in tumor tissue versus comparable normal tissue have been reported; in other cases, including liver cancer, a decrease in ferritin is seen. 179 New forms of ferritin may be involved in certain situations: Moroz and coworkers have described a novel isoform of ferritin that is elevated in the serum of patients with neoplastic breast disease as well as during pregnancy and HIV infection.…”

Genetic Variability in Iron-Related Oxidative Stress Pathways (Nrf2, NQ01, NOS3, andHO-1), Iron Intake, and Risk of Postmenopausal Breast Cancer

“…Iron can cause oxidative tissue damage by catalyzing HaberWeiss and Fenton reactions that convert hydrogen peroxide (H 2 O 2 ) to free radicals (9)(10)(11)(12). In women, neoplastic breast tissue contains higher levels of iron and ferritin compared with normal tissue (13,14), and rats fed excess iron develop earlier and more numerous mammary tumors (15), whereas those fed iron-deficient diets are protected (16). Currently, some epidemiologic studies support a role for excessive dietary iron intake and risk of total cancers (17)(18)(19) as well as risk of lung and colon cancers (17,(20)(21)(22)(23), but there are few data on relationships with breast cancer (24)(25)(26).…”

Acute Phase Proteins: Ferritin and Ferritin Isoforms

“…In patients with solid tumours, such as pancreatic carcinoma, lung cancer and hepatoma, there is a particularly high incidence of elevated plasma ferritin, and in patients with breast cancer, with metastasis, ferritin plasma concentrations are commonly elevated (Worwood, 1982). It is of interest that ferritin levels in breast cancer are not only raised in the plasma, but also in breast tissue (Ionescu et al, 2006;Weinstein et al, 1982). Squamous cell carcinoma of the head and neck is marked by increased plasma ferritin concentrations, which remains high in patients with a poor prognosis in contrast to patients with a favourable prognosis (Maxim & Veltri, 1986).…”

“…It is suggested that an increase in the labile iron pool plays a role, since depletion of the labile iron pool and a decrease in ROS suppress the migration of tumour cells (Zhang et al, 2009). In contrast, up-regulation of intracellular H-subunit rich ferritins has been shown in several studies (Elliot et al, 1993;Shpeleva et al, 2011;Weinstein et al, 1982). In the study by Shpeleva et al, involving human breast cancer, an increase in the expression of the H-subunit and Lsubunit intracellular levels of ferritin was associated with a decrease in the labile iron pool (Shpeleva et al, 2011).…”

“…As plasma ferritin is generally a secretory product of cells it is unlikely that intracellular ferritin levels would be low in conjunction with excessively high extracellular levels. In fact, measurements of tissue ferritin levels showed, in general, increased levels of ferritin in malignant breast tissues, at least in advanced more aggressive stages (Elliot et al, 1993;Shpeleva et al, 2011;Weinstein et al, 1982). As a rule, one would expect these high intracellular ferritin levels to decrease bio-available iron -which is contrary to the requirement of cancer cells.…”