Expression of transglutaminase-2 (TGM2) in the prognosis of female invasive breast cancer

BACKGROUND: Transglutaminase 2 (TGM2) is a protein expressed in several isoforms in both intra- and extra-cellular tissue compartments. It has multiple functions that are important in cancer biology and several small studies have suggested expression of TGM2 in breast cancers is associated with a poorer prognosis. The aim of this study was to evaluate the role of intra-cellular and extra-cellular TGM2 expression in breast cancer and to determine whether there were any differences by hormone receptor status.METHODS: We carried out TGM2 immunostaining of tissue micro-arrays comprising 2169 tumour cores and scored these for both intra- and extra-cellular and expression.RESULTS: Intra-cellular (tumour cell) TGM2 positivity was associated with a better prognosis (HR = 0.74, 95% CI 0.59–0.92) with a larger effect stronger in hormone-receptor-negative cases (HR = 0.56, 95% CI 0.37–0.85). Extra-cellular (stromal) TGM2 expression was associated with a poorer prognosis (HR = 1.47, 95% CI 1.06–2.03) with a stronger association in hormone-receptor-positive cases (HR = 1.60, 95% CI 1.09–2.34).CONCLUSION: Tissue compartment and hormone receptor status differences in the effect of TGM2 expression on clinical outcomes of breast cancer may reflect the different functions of TGM2.</p

SNPs associated with ILC (P<5×10⁻⁸) or LCIS (P<0.05) in a pooled lobular analysis (GLACIER and BCAC).

<p>SNPs associated with ILC (P<5×10⁻⁸) or LCIS (P<0.05) in a pooled lobular analysis (GLACIER and BCAC).</p

rs11977670, chromosome 7:139942304 G>A, and association ILC in populations of European ancestry.

<p>rs11977670, chromosome 7:139942304 G>A, and association ILC in populations of European ancestry.</p

Forest plot for rs11977670.

<p>Forest plot for rs11977670.</p

SNPs showing differential lobular and ductal associations with breast cancer risk in BCAC subjects (ER+ tumours only).

<p>SNPs showing differential lobular and ductal associations with breast cancer risk in BCAC subjects (ER+ tumours only).</p

Association with risk of breast cancer for rs11977670 stratified by breast cancer tumour subtypes (Pooled analysis, BCAC, GLACIER, UK PHASE II).

<p>Association with risk of breast cancer for rs11977670 stratified by breast cancer tumour subtypes (Pooled analysis, BCAC, GLACIER, UK PHASE II).</p

Lobular cancer study design.

<p>Lobular cancer study design.</p