Pathological and Molecular Analysis of Spontaneous Canine Mammary Carcinomas and its Prognostic implications

Abstract

Abstract Purpose: The canine mammary tumours (CMT) and human breast cancers (HBC) are postulated to resemble each other in genesis, progression, presentation and prognostication. Thus, studies involving naturally occurring CMT may aid in better understanding of HBC. The study also aims at replicating the techniques used to study the HBC in CMT and to find whether the canine model can be utilized for HBC research and also provide diagnostic methods for patients with CMT. Methods: Samples from spontaneous CMT cases were collected and a cohort of canine mammary carcinomas (CMC) was utilised for this study after histopathological examination and grading. Immunophenotyping and identifying the cancer stem cells (CSC) which are the most acclaimed cause of recurrence, metastasis, and treatment failures in CMC was performed by using suitable markers. Results: Expression of CD44+/24-/low CSC phenotype, CD24 overexpression, ALDH1 in higher grades, decreased E cadherin and increased N cadherin in recurrence/ metastasis were observed by immunohistochemistry. The qRTPCR results showed increased Oct-4, Sox-2, Nanog expression in higher grades of tumours, while the E and N cadherin switch was observed in recurrent/ metastatic cases. A survival analysis of a 36 months follow-up study revealed that prognosis was poor in patients with higher grades and in CMC with CD44+/24-/low or CD24 overexpression. Conclusion: It could be deciphered from the study that the human and canine breast cancers share common diagnostic and prognostic signatures and can serve as better model to study the human disease.