Immunohistochemical changes in the mammary gland following experimental local mycobacterial exposure

Abstract

Mammary tuberculosis and other mycobacterial forms of granulomatous mastitis are uncommon but clinically important lesions that closely mimic carcinoma, and the receptor and proliferative reorganisation they induce in the gland is poorly characterised. This study quantified the proliferation marker Ki-67 and the estrogen (ER) and progesterone (PR) receptors in the mammary gland of outbred female rats after local mycobacterial exposure, and tested whether oral curcumin corrects the resulting changes. One hundred rats were assigned to an intact control group, a group receiving a complete Freund adjuvant–killed mycobacterial emulsion adjacent to the mammary gland, and a group receiving the same exposure followed by oral curcumin, and were studied at 4 and 9 months of age. Paraffin sections were immunostained for Ki-67, ER and PR and quantified by positive-cell detection in QuPath 0.5.1; positivity indices were compared by chi-square or Fisher exact tests with Benjamini–Hochberg control of the false-discovery rate. Mycobacterial exposure lowered the Ki-67 index by 47% at 4 months and 36% at 9 months and the PR index by about 50% and 42% (all adjusted p < 0.01), and reduced the ER index by roughly one-half, although the ER comparison did not survive correction owing to few detected nuclei. Curcumin restored about 61% of the lost proliferative activity at 4 months and produced smaller, non-significant gains in receptor expression. Local mycobacterial exposure therefore suppresses epithelial proliferation and hormone-receptor expression in the mammary gland, and curcumin partially reverses the proliferative component, supporting its evaluation as an adjunct natural biocorrector.