Establishing histopathological criteria for breast cancer research

Andrea Werbach¹, María Jimena Rodríguez¹, María Cecilia Perrone¹, Ariel Zwenger², Diego Enrico³, Pablo Mandó³, Mora Amat³, Victoria Costanzo³, Estrella Levy³, Virginia Novaro¹

Breast cancer is a heterogeneous disease with varied morphological appearance, molecular features, behavior and response to therapy. Though these varieties are well-established and rely on clinical and histopathological classification, research demands the continuous study of the ever-increasing knowledge on the mechanisms behind disease progression and associated risk factors. In this context, novel diagnostic and therapeutic techniques may be developed through experimentation on animal models. This dynamic interplay between clinical practice and experimental oncology faces new challenges, especially when clinicians and biologists interact at the bench. Here, we present our experience in unifying analytical criteria to classify and interpret histopathological studies beyond current standards. In biopsies of human breast carcinomas and mouse tumor xenografts, we evaluated histological and nuclear indexes to establish tumor grade. We evaluated the extent of necrosis in growing and shrinking tumors after therapy and the characteristics of tumor edges, whether they are expansive or infiltrating. After immunohistological studies, we designed a score for particular proteins in the PI3K/AKT/mTOR and cyclin D1/Rb pathways considering the percentage of positive tumor cells and the intensity of the staining. In conclusion, we established new approaches considering the research interest and the standard convention criteria with a dynamic interaction between scientists and pathologists.