ERα, HER-2, pan-RAS, p53, and aromatase expression in spontaneous malignant canine mammary tumors: Prognostic relevance and association with clinicohistological parameters.

Aim: The interlacing interaction between proto-oncoproteins and tumor-suppressing proteins in malignant canine mammary tumors (mCMT) microenvironment remains largely unexplored. The present study intended to decipher the i) association between the intratumoral expression of ERα, HER-2, pan-RAS, p53 and aromatase, ii) their relationship with the clinicohistological parameters and serum sex hormones, and iii) their prognostic relevance in mCMT.

Materials And Methods: Tumor samples from animals with mCMT (n = 27) were subjected to histopathology and immunohistochemistry for ERα, HER-2, pan-RAS, p53, and aromatase. Serum estradiol and progesterone levels from dogs with mCMT and healthy dogs (n = 10) were estimated using chemiluminescence immunoassay. Kaplan-Meier analysis (log-rank test), univariable and multivariable Cox regression, and Mann-Whitney U test were employed for statistical analysis.

Results: The expression of aromatase, ERα, pan-RAS, p53, and HER-2 were detected in 100 %, 88 %, 67 %, 12 % and 11 % of mCMT cases, respectively. Serum estradiol and progesterone were significantly higher in mCMT-affiliated patients than healthy dogs. Also, a positive association of ERα expression with aromatase (stromal component) and HER2 expression in mCMT patients was detected. Furthermore, intratumoral aromatase expression and p53 overexpression were correlated with tumor size and angiogenesis, respectively. No relationship was detected between other tumor markers, serum steroid hormones and clinicohistological parameters. P53 overexpression was associated with poor survival in mCMT patients.

Conclusion: Overexpression of aromatase and p53 overexpression has clinical relevance in mCMT, and an intratumoral ERα expression is positively associated with HER-2 expression and aromatase production by stromal components.