Quantification of tumor-associated stroma, collagen, and desmoplasia and their role in prognostication of feline mammary carcinomas

Tumoral stroma as a key element of the tumor microenvironment has gained increased relevance in recent oncology studies. The tumor-stroma ratio (TSR) has been validated as a prognostic factor in human breast cancer. In feline mammary carcinomas (FMCs), few studies have delved into tumor stromal components, such as collagen and fibroblasts, and none have evaluated the TSR. Herein, multiple approaches for assessing tumor stroma and collagen in FMCs of 129 queens were used, including semi-quantitative evaluations in hematoxylin and eosin and in Picrosirius stainined sections and digital quantification by image analysis using ImageJ software. The desmoplasia-to-collagen ratio (DCR) was also computed using the image analysis results. A weak agreement was obtained between semi-quantitative and quantitative values of TSR and collagen amount; however, the majority of samples were scored below 50%, irrespective of the method, with a DCR above 50% in most of the carcinomas. Overall, clinical stage III and a more pronounced inflammatory infiltrate were consistently overrepresented in the increased stroma, total collagen, and desmoplasia groups. In the univariate survival analysis, a high amount of stroma, desmoplasia, and increased DCR were associated with shorter survival. Moreover, quantitative variables of TSR, desmoplasia, and DCR emerged as independent prognostic factors in multivariate models. The TSR and, specifically, the amount of collagen within the tumor stroma appear to have a role in the biological behavior of FMCs. Ancillary techniques for quantifying TSR, desmoplasia, and DCR provide additional prognostic information, and efforts should be made to include them in the routine post-surgical evaluations of FMC cases.