Introduction Iron is essential for the proliferation of all mammalian cells. We previously showed that the expression of iron transport proteins are altered in colorectal cancer (CRC) [1]. This is the first study to examine whether iron therapy further alters iron transport expression at both protein and mRNA level in human CRC.

Method 30 patients with colorectal adenocarcinoma and pre-operative iron deficiency anaemia received iron therapy a minimum of 2 weeks before surgery as part of the IVICA trial (15 oral ferrous sulphate, 15 intravenous (IV) ferric carboxymaltose) [2]. Paired normal and tumour tissue from surgical resection were analysed for iron loading using Prussian blue staining; TfR1, DMT1 and ferroportin proteins using immunohistochemistry and IREB2, FTH1, TFRC and DMT1 mRNA using real time PCR. Expression was compared between normal and tumour and treatment groups.

Results Iron loading was increased in tumour tissues compared to normal tissues (p<0.05). Distribution of iron deposits appeared to differ depending on route of iron therapy. Iron transporter proteins TfR1, ferroportin and DMT1 had higher immunoreactivity in tumour compared to normal tissue. Further, all 3 became partially mislocalised to cytoplasm whereas in normal tissues expression was membranous. In tumour, RT-PCR showed IREB2 was reduced but with an increase in iron importers TFRC (TFR1) (p<0.03) and DMT1 (p<0.01) and a reduction in FTH1 encoding ferritin heavy chain for storage (p<0.05). FTH1 mRNA levels were significantly reduced with IV iron treatment in tumour tissues compared with those receiving oral treatment (p>0.001). No significant differences in the other iron transporters were seen between treatment groups.

Conclusion Similar to our previous findings iron loading is seen in CRC through an increase in the expression of iron transporters compared to normal colon. When the two treatment arms were compared the only significant difference seen was that tumour ferritin expression was higher in those receiving oral iron. This might suggest that iron supplementation by IV compared to oral iron lead to a differential effect on intracellular iron loading. Further work is needed to determine if IV iron supplementation is safer due to differential compartmentalisation of the iron within the mucosa which might avoid tumour cell iron loading.

References

1. . Brookes, MJ, et al. Modulation of iron transport proteins in human colorectal carcinogenesis. Gut2006;55(10):1449–60.

2. . Keeler, BD, et al. Randomised clinical trial of preoperative oral versus intravenous iron in anaemic patients with colorectal cancerBr J Surg, 2017;104(3):214–221.

Disclosure of Interest None Declared