Does thyroid peroxidase provide an antigenic link between thyroid autoimmunity and breast cancer?

[helvella]

The rate at which interesting thyroid-related papers are published is astonishing. Here another paper with a handsome contribution from the Thyroid Research Group in Cardiff. Hopefully, slowly, a more comprehensive and coherent picture of thyroid and related diseases appears out of the mists.

In this abstract, the very first sentence is really quite a surprise (to me). And it really makes me question the whole issue of what the TPO antibodies do, why they are present, and what the appropriate interpretations of test numbers might be.

Int J Cancer. 2013 Sep 30. doi: 10.1002/ijc.28493. [Epub ahead of print]

Does thyroid peroxidase provide an antigenic link between thyroid autoimmunity and breast cancer?

Muller I, Giani C, Zhang L, Grennan-Jones FA, Fiore E, Belardi V, Rosellini V, Funel N, Campani D, Giustarini E, Lewis MD, Bakhsh AD, Roncella M, Ghilli M, Vitti P, Dayan CM, Ludgate ME.

Source

Thyroid Research Group, Institute of Molecular © Experimental Medicine, School of Medicine, Cardiff University, UK; Department of Endocrinology, University of Pisa, Italy.

Abstract

Women with breast cancer (BC) and anti thyroid peroxidase (TPO) autoantibodies (TPOAb) have a better prognosis than women lacking TPOAb. Sera from women with TPOAb displayed immunoreactivity to BC tissue by immunofluorescence that was not apparent in women without TPOAb. We hypothesize a BC/thyroid shared antigen that provides a target for humoral or cell-mediated immune activity; candidates include the sodium/iodide symporter (NIS, expressed in thyroid and BC), cross-reacting epitopes in TPO and lactoperoxidase (LPO) or TPO itself. Since the association is with TPOAb, we investigated TPO expression in BC, breast peri-tumoral tissue (PT), other tissues (tumoral and not) and thyroid as positive control. Transcripts for known and novel TPO isoforms were detected in BC (n=8) and PT (n=8) but at approximately 104 fold lower than in thyroid while in non-BC tumours (n=5) they were at the limit of detection. TPO was expressed also in adipose tissue (n=17), 103 fold lower than in thyroid. Full length TPO (Mr 105-110 kDa) was detected in western blots in the majority of examined tissues; pre-absorption of the TPO antibody with recombinant TPO (but not LPO) reduced the signal, indicating specificity. The same occurred with some lower molecular weight bands, which could correspond to smaller TPO transcript isoforms, present in all samples. In conclusion TPO is weakly expressed in BC and other tissues; this could partly explain the high frequency and protective role of TPOAb in BC patients. Further studies will investigate tissue specificity, function and immunogenicity of the novel TPO variants (some BC-specific) identified. © 2013 Wiley Periodicals, Inc.

Copyright © 2013 UICC.

KEYWORDS:

Alternative Splicing, Antigen, Breast cancer, Thyroid autoimmunity, Thyroid peroxidase

PMID:

24114667

[PubMed - as supplied by publisher]

ncbi.nlm.nih.gov/pubmed/241...

Rod

Image: Illustration of antibody showing constant and variable portions, light and heavy chains and disulphide bonds.

30 August 2008 : Recreated jpg originally uploaded by Muntasir Alam : Author DigitalShuttermonkey

[Marz]

Thank you Rod. They seem to do great research in Pisa Italy - they were also the creators of the research on The Thyroid and Heart Failure - book of the same name. Apparently it was the first time research took place where the Endos and the Cardios put their heads together.

Very interesting post.....

[helvella Administrator in reply to Marz]

Sometimes it feels that it is left to patients to make links between the various branches of medicine. In my book, links between heart and thyroid have been obvious since the very early days of thyroid understanding - round about a century ago.

Rod

[tilly83]

I am feeling very dim looking at this, like a mathematical equation, Rod as you seem to have got your intelligent head around it - what in a nutshell does it actually mean? thanks!!!!!!

[Hidden in reply to tilly83]

OMG, me to! Is it saying if you have TPOAb it protects you from getting breast cancer, or is is saying if you have breast cancer the TPOAb have a protective effect? Over to you Rod...

[tilly83 in reply to Hidden]

no wonder I struggle with computers and my Iphone"!!!!!!!!!!!!!!!

[helvella Administrator in reply to tilly83]

People with breast cancer who ALSO have Thyroid Peroxidase antibodies (usually regarded as a hallmark of Hashimoto's) tend to do better than those who do NOT have TPOab.

This might be because breast cancer tissue actually makes some form of TPO in small amounts.

Interestingly, small amounts of TPO can be found in adipose tissue (fat cells).

More research needed!

(At least, I hope I got that right. If anyone thinks otherwise, please pile in.)

Rod

[sarahstevenson]

That's how I read it - interesting posting and article - thanks Rod

[tilly83]

Thanks Rod, felt I had all the intellectual flexibility of a Kit Kat there... best M