Immunohistochemical evaluation of STAT3-p-tyr705 expression in feline mammary gland tumours and correlation with histologic grade

Abstract

STAT3 (signal transducer and activator of transcription 3) is a cytoplasmic transcription factor that plays a role in the G1 to S phase cell-cycle transition and is induced by cytokines and growth factors. The expression of STAT3 phosphorylated on tyrosine 705 (STAT3-p-tyr705) in normal, hyperplastic and neoplastic feline mammary gland tissue was assessed by immunohistochemistry in 45 cats. The samples included 4 normal mammary non-lactating tissues, 9 hyperplastic tissues (5 fibroepithelial hyperplasia and 4 lobular epithelial hyperplasia), 2 benign tumours (1 complex adenoma, and 1 simple adenoma), and 30 carcinomas (18 simple tubular papillary, 6 simple tubular, 2 simple solid, 3 cribriform, and 1 adenosquamous carcinoma). For immunohistochemistry, tissue sections were incubated with an anti-STAT3-p-tyr705 monoclonal antibody and visualized with EnVision-DAB polymer. STAT3-p-tyr705 positivity was quantified in a semi-quantitative manner. All positive samples showed cytoplasmic and/or nuclear positivity. Normal non-lactating mammary tissue showed a low number of positive cells, similar to hyperplastic tissue. In neoplastic tissues, a high number of positive cells with a moderate to intense reaction was observed. Moreover, a correlation was observed between nuclear positivity for STAT3-p-tyr705 and histologic grade ( P = 0.013; r = 0.447), tubular formation ( P = 0.043; r = 0.820), and mitotic activity ( P < 0.0001; r = 0.689). In contrast, no such correlations were observed for cytoplasmic reactivity of STAT3-p-tyr705. A significant difference was observed between malignant lesions and hyperplasia with regards to expression of STAT3-p-tyr 705 in the cytoplasm ( P = 0.008; U = 59.00) and nuclei ( P = 0.002; U = 47.00). These results confirm previous our data and reinforce the potential role of STAT3 in malignancy as reported for human breast cancer and other sporadic tumours.