Expression of peroxisome proliferator-activated receptor alpha in feline mammary carcinomas

This study aimed to investigate the expression patterns of peroxisome proliferator-activated receptor alpha (PPARα) in normal tissue and feline mammary carcinomas. Thirty feline mammary carcinomas (FMCs) and eight normal mammary tissues were used in this study. In the same FMC cats, tissues were collected from 2 regions which are the neoplastic tissue and the adjacent non-neoplastic tissues. The study was composed of three parts: (1) clinical data collection and histopathological diagnosis; (2) Immunohistochemistry (IHC) evaluation of PPARα, Ki-67, and proliferating cell nuclear antigen (PCNA); and (3) Western blot analysis of PPARα isoforms. The results revealed no significant differences in PPARα expression, Ki-67 index, PCNA index, or mitotic index (MI) with respect to breed, age, tumor number, size, suppuration, or necrosis (P>0.05). In contrast, significant associations were observed for fertile status, histological grade, and metastatic condition. All cases were classified as tubular carcinomas, with 56.67% grade I and 43.33% grade II tumors, and lymph node metastasis was detected in 50% of cases. IHC demonstrated that PPARα was expressed in both normal and neoplastic tissues, mainly localized in the cytoplasm of glandular, ductal, and myoepithelial cells with occasional nuclear staining. The PPARα H-score increased significantly from normal (31.35±7.041), non-neoplastic (79.87±11.76) (PP<0.01), and neoplastic regions (128.6±12.76) (P<0.01). Ki-67 and mitotic indices also increased in late-stage and grade II of FMCs. A strong positive correlation was observed between PPARα H-score and both Ki-67 index (P<0.01) and mitotic index (P<0.01), indicating that PPARα expression is linked to tumor proliferation. Western blot analysis identified three major PPARα isoforms: a full-length 52KDa, a truncated 31KDa, and a high molecular weight 110KDa band. The 31KDa isoform was upregulated in FMCs compared to normal mammary tissues, whereas the 52KDa and 110KDa isoforms were markedly reduced or absent, suggesting isoform alterations during tumorigenesis. In conclusion, PPARα is upregulated in FMCs and shows correlation with tumor grade and proliferative activity. These findings indicate that PPARα plays an important role in FMCs progression and may serve as a prognostic biomarker and potential therapeutic target.