Tissue array-based expression of transglutaminase-2 in human breast and ovarian cancer

Abstract

Transglutaminase-2 is involved in the physiological regulation of cell growth, but has also been associated with a number of cancer-associated features such as cell adhesion, metastasis and extracellular matrix modulation. Despite its importance in tumor cell progression and survival, relatively little is known about its expression in human malignancies. We have therefore investigated the transglutaminase-2 expression pattern in breast and ovarian cancer by using tissue arrays which contained 57 invasive breast cancer biopsies and 62 ovarian cancers, and compared it to transglutaminase-2 protein levels in normal human tissues. By using immunohistochemistry, transglutaminase-2 protein was detected in 48 of 57 breast tumors (84%), with epithelial expression in 26 of 41 (63%) ductal invasive carcinomas and in all 6 (100%) lobular invasive carcinomas. Stromal transglutaminase-2 was present in 14 of 41 (34%) ductal subtypes and in 4 of 6 (67%) lobular subtypes, which is in sharp contrast to the infrequent expression in normal breast stroma (P<0.001, Mann-Whitney test) and somewhat also in normal breast epithelium (P = 0.065, Mann-Whitney test). In most other human tissues, transglutaminase-2 protein was less frequent and usually confined to either the epithelium or in adjacent stroma. In ovarian tumors, the protein was detected in 36 of the 62 cases (58%), and seen in all histological subtypes. Taken together, we have demonstrated increased transglutaminase-2 protein expression in both malignant breast epithelium and surrounding stroma, although its selective spatial expression pattern in normal tissues also indicates a physiological role in stromal-epithelial interactions.