Intratumoral collagen index predicts mortality and survival in canine cutaneous mast cell tumours

Abstract

Background -Mast cell tumours (MCTs) constitute almost 25% of cutaneous neoplasms in dogs. Their biological behaviour is predicted using histopathological grading which is based on several subjective criteria that are vulnerable to intra-and interobserver variability. To improve the prediction of the biological behaviour, several complementary markers have been studied. The integrity of the extracellular matrix (ECM) may play a protective role against tumoral progression, and favour cellular proliferation, angiogenesis, invasion and metastases when altered.Hypothesis/Objectives -To evaluate the quantification of collagen and elastic fibres as prognostic markers for MCTs.Animals -Thirty-eight random cases of canine cutaneous MCT surgically treated with wide margins were included.Methods and materials -Intratumoral collagen and elastic fibres were identified and quantified on histological sections stained with Masson's trichrome, Picrosirius red and Verhoeff; the results were compared with histopathological grades, mortality due to the disease and postsurgical survival.Results -Morphometric analysis revealed a significant relationship between histopathological grade and intratumoral collagen index (CoI). In addition, the CoI was considered an independent indicator for mortality and postsurgical survival.Conclusions and clinical importance -These results support the importance of the CoI in the grading and prognosis of MCTs, suggesting that preservation and/or synthesis of collagen have the potential to become targets for MCT therapeutics.

VEGF Expression, Cellular Infiltration, and Intratumoral Collagen Levels after Electroporation-Based Treatment of Dogs with Cutaneous Squamous Cell Carcinoma

“…One of the advantages of using MT staining is its low-cost and practical implementation compared to other techniques. It has been observed that higher intratumoral collagen levels are associated with lower-grade canine cutaneous mast cell tumors, with greater survival times in those with a value lower than 9.25% [29,32]. In female dogs with mammary tumors, aggressive carcinomas with shorter collagen fibers are present, which directly affects the survival time [34].…”

“…Masson's trichrome (MT) staining is a low-cost, practical method used for assessing the ECM, which is a major component of the tumor microenvironment. High intratumoral collagen levels have been associated with increased survival time in dogs with low-grade cutaneous mast cell tumors [29,32]. Compounds that inhibit the adhesion of tumor cells to the ECM have also been shown to prevent metastasis [33].…”

Prognostic Value of Intratumoral Collagen Quantification in Canine Oral Melanomas

“…In the present study, the ICI was not an efficient prognostic marker for canine OMs. Despite the fact that density and alignment of the collagen fibers are considered prognostic markers for human breast cancer, [26][27][28] and that the ICI is an indicator of mortality and postsurgical survival for canine cutaneous mast cell tumors, 31 the values obtained for OMs were very low and similar between lesions. The source of the tumors included in the present study, specialized oncology and dentistry services, might have influenced our results, perhaps selecting for cases of higher malignancy and, consequently, melanocytic tumors with higher cellularity and less stroma.…”

“…20,26,27 Additional studies have elucidated other ECM roles in tumor invasion and metastasis. 22,[28][29][30][31] Invasion and metastasis formation depend on enzymatic degradation, especially by matrix metalloproteinases, whose expression is also influenced by ECM members. 20,22,29 Compounds that inhibit tumor cell adhesion to the ECM are capable of preventing metastases, demonstrating the importance of studies to characterize ECM alterations in cancer.…”

“…30 Moreover, intratumoral collagen index also showed prognostic value for this neoplasm, with the advantage of being evaluated through histochemical staining, considerably reducing the costs of the analysis. 31 The purpose of the present research was to investigate the prognostic value of the Intratumoral collagen index (ICI) as an indicator of postsurgical survival and its relation with other prognostic markers for canine oral melanomas.…”