Hormone receptor discrepancy and molecular subtype changes in canine mammary carcinomas and synchronous lymph node metastasis

Abstract

Mammary tumors are the most prevalent neoplasms in intact female dogs; up to 50 % are considered malignant and have the potential to metastasize to regional lymph node and distant organs. Changes in tumor molecular subtype, including its receptor status, can occur during mammary tumor progression. This study aimed to explore hormone receptor discrepancies and the relationship between molecular subtypes in primary mammary tumors (PTs) and paired lymph node metastases (LNMs). Thirty PTs samples and paired LNMs were evaluated for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 through immunohistochemistry. After analysis, the discordance rates were 11.1 %, 26.9 %, and 11.5 %, for ER, PR and Ki-67, respectively. All samples were negative for HER2. The molecular subtypes showed a 40.7 % discordance rate between PTs and matched LNMs. Additionally, 44.4 % of luminal A-like, 36.4 % of luminal B-like and 42.8 % of triple-negatives in PTs displayed different subtypes in the corresponding LNMs, respectively. Among discordant cases, five progressed to subtypes usually associated with a poor prognosis, while six presented a transition to subtypes frequently associated with a favorable prognosis. Discordance in molecular subtypes between PTs and LNMs may lead to therapeutic failures. Therefore, the assessment of molecular subtypes at both sites is crucial and could offer potential for the development of more accurate prognostic and treatment models.