Immunostaining for VEGF and Decorin Predicts Poor Survival and Recurrence in Canine Soft Tissue Sarcoma

Simple Summary Soft tissue sarcomas are one of the most common malignant tumours affecting the dog. Surgical removal is curative for the majority of patients, but local recurrence can develop in almost 20% of patients. Local recurrence is the most common reason for euthanasia, and a significantly shorter survival time. A recurrent tumour most likely arises from isolated tumour cells that remain in the wound bed following removal of all of the visible tumour. This study seeks to identify whether the presence of two proteins—vascular endothelial growth factor (VEGF) and decorin—within the tumour may assist with prediction of tumour recurrence. Both proteins are known to play important roles in enabling development of new blood supply to a developing tumour. It was hypothesised that if the original tumour contained proportions of these proteins known to be important for vascular development, this may provide residual cancer cells with a more enhanced ability to recrudesce into a visible recurrence. This study showed that recurrence following surgery was more likely if the tumour had a high level of staining for VEGF and/or did not stain for decorin. This study supports the hypothesis, but further investigation is required to validate this finding. Abstract The aim of this study was to investigate whether using immunohistochemistry to detect the angiogenic proteins vascular endothelial growth factor (VEGF) and decorin can help predict the risk of local recurrence of, or death from, canine soft tissue sarcoma (STS). VEGF and decorin were detected using validated immunohistochemical methods on 100 formalin-fixed paraffin-embedded samples of canine STS. The tumours had been resected previously, with clinical outcome determined by questionnaire. Each slide was assessed by light microscopy and the pattern of immunostaining with VEGF and decorin determined. Patterns of immunostaining were then analysed to detect associations with outcome measures of local recurrence and tumour-related death. High VEGF immunostaining was significantly (p < 0.001) associated with both increased local recurrence and reduced survival time. The distribution of decorin immunostaining within the tumour was significantly associated with survival time (p = 0.04) and local tumour recurrence (p = 0.02). When VEGF and decorin scores were combined, STS with both high VEGF and low decorin immunostaining were more likely to recur or cause patient death (p < 0.001). The results of this study suggest that immunostaining of VEGF and decorin may help predict the risk of local recurrence of canine STS.

[1]  W. Eward,et al.  Evaluating the relevance of surgical margins. Part one: The problems with current methodology. , 2022, Veterinary and comparative oncology.

[2]  Sun Xin,et al.  Correlation of vascular endothelial growth factor with survival and pathological characteristics of patients with osteosarcoma: A systematic review and meta-analysis. , 2022, European journal of cancer care.

[3]  Ai-ni Chen,et al.  The VEGF expression associated with prognosis in patients with intrahepatic cholangiocarcinoma: a systematic review and meta-analysis , 2022, World Journal of Surgical Oncology.

[4]  F. Diaz-Quijano Sample allocation balancing overall representativeness and stratum precision. , 2018, Annals of epidemiology.

[5]  A. Laurenzana,et al.  The acidic microenvironment as a possible niche of dormant tumor cells , 2017, Cellular and Molecular Life Sciences.

[6]  Xiaomei Wang,et al.  The biological basis of degenerative disc disease: proteomic and biomechanical analysis of the canine intervertebral disc , 2015, Arthritis Research & Therapy.

[7]  G. Polton,et al.  Canine soft tissue sarcoma managed in first opinion practice: outcome in 350 cases. , 2014, Veterinary surgery : VS.

[8]  M. Dagli,et al.  Serum vascular endothelial growth factor in dogs with soft tissue sarcomas. , 2013, Veterinary and comparative oncology.

[9]  Wancai Yang,et al.  Chinese a Nti鄄 Cancer a Ssociation , 2022 .

[10]  B. Corcoran,et al.  Canine tissue-specific expression of multiple small leucine rich proteoglycans. , 2012, Veterinary journal.

[11]  K. Smith,et al.  Vascular endothelial growth factor (VEGF) and VEGF receptor expression in biopsy samples of liver from dogs with congenital portosystemic shunts. , 2012, Journal of comparative pathology.

[12]  Jessica E. S. Shay,et al.  Effects of hypoxia and HIFs on cancer metabolism , 2012, International Journal of Hematology.

[13]  J. Condeelis,et al.  Microenvironments dictating tumor cell dormancy. , 2012, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[14]  B. Powers,et al.  Prognostic Factors for Cutaneous and Subcutaneous Soft Tissue Sarcomas in Dogs , 2011, Veterinary pathology.

[15]  T. Dønnem,et al.  Profiling of VEGFs and VEGFRs as Prognostic Factors in Soft Tissue Sarcoma: VEGFR-3 Is an Independent Predictor of Poor Prognosis , 2010, PloS one.

[16]  M. Dagli,et al.  Vascular Endothelial Growth Factor Expression and Microvascular Density in Soft Tissue Sarcomas in Dogs , 2010, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[17]  K. Mcsporran Histologic Grade Predicts Recurrence for Marginally Excised Canine Subcutaneous Soft Tissue Sarcomas , 2009, Veterinary pathology.

[18]  R. Iozzo,et al.  Tumor microenvironment: Modulation by decorin and related molecules harboring leucine‐rich tandem motifs , 2008, International journal of cancer.

[19]  M. Söderström,et al.  Differential Expression of Decorin by Human Malignant and Benign Vascular Tumors , 2008, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[20]  A. Uchida,et al.  Expression of decorin, a small leucine‐rich proteoglycan, as a prognostic factor in soft tissue tumors , 2007, Journal of surgical oncology.

[21]  S. Platt,et al.  Vascular endothelial growth factor expression in canine intracranial meningiomas and association with patient survival. , 2006, Journal of veterinary internal medicine.

[22]  E. Pakos,et al.  Expression of vascular endothelial growth factor and its receptor, KDR/Flk-1, in soft tissue sarcomas. , 2005, Anticancer research.

[23]  Bart Landuyt,et al.  Vascular Endothelial Growth Factor and Angiogenesis , 2004, Pharmacological Reviews.

[24]  R. Iozzo,et al.  Decorin suppresses tumor cell-mediated angiogenesis , 2002, Oncogene.

[25]  B. Eisenberg,et al.  Vascular Endothelial Growth Factor and Soft Tissue Sarcomas: Tumor Expression Correlates With Grade , 2001, Annals of Surgical Oncology.

[26]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[27]  P. Carmeliet,et al.  Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis , 1998, Nature.

[28]  C. A. Kuntz,et al.  Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996). , 1997, Journal of the American Veterinary Medical Association.

[29]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[30]  B Sundell,et al.  Soft-tissue sarcomas. , 1979, British medical journal.

[31]  J. Folkman Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.