Expression of HIF-1α and VEGF in feline mammary gland carcinomas: Association with pathological characteristics and clinical outcomes
Journal
BMC Veterinary Research
Journal Volume
16
Journal Issue
1
Date Issued
2020
Author(s)
Chen, B.
Lin, S.J.-H.
Li, W.-T.
Chu, P.-Y.
Lee, C.-C.
Nakayama, H.
Abstract
Background: The microenvironment within solid malignant tumors, including feline mammary gland carcinomas (FMGCs), is commonly hypoxic, possibly due to the lack of functional blood vessels in rapidly proliferating neoplastic tissue. Malignant cells can undergo genetic and adaptive changes that prevent them from dying due to oxygen deprivation through expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Therefore, HIF-1α and VEGF are ideal biomarkers for cancer therapy and prognostic evaluation. The aims of this study were to evaluate the expression of HIF-1α and VEGF in feline mammary carcinomas and analyze their correlations with clinical and pathological factors, such as clinical stage, histologic grading, regional metastasis, and overall survival rate. Results: Paraffin-embedded tissue samples collected from 72 cats with FMGCs were retrospectively studied. Histologic pattern and histologic grading (Elston and Ellis grading system) of these FMGCs were determined. Our data indicated that grade II tubulopapillary carcinomas (43/72, 59.7%) prevailed in this study, and most FMCGs showed apparent necrosis, squamous metaplasia, and intratumoral stromal response. According to the results of immunohistochemical (IHC) stainings performed in tissue microarrays (TMAs), HIF-1α and VEGF overexpressions were respectively noted in 69.4% (50/72) and 77.8% (56/72) of FMGC cases. Chi-square test showed no correlation of HIF-1α overexpression with clinical and pathological factors. VEGF overexpression was significantly correlated with histologic pattern (p = 0.021), stromal response (p = 0.048), squamous metaplasia (p = 0.001), and lymphovascular invasion (p = 0.007). However, neither HIF-1α nor VEGF overexpression was correlated with histologic grading and metastasis. Of 38 cats with 1-year follow-up, IHC stainings of HIF-1α and VEGF were performed on whole tissue sections. The results showed that overexpression of HIF-1α was significantly correlated with the overall survival rate (p < 0.05) (log-rank test), whereas there was no significant correlation between VEGF overexpression and overall survival rate. Conclusions: This study suggests that the overexpression of HIF-1α may indicate poor prognosis/overall survival rate in cats with FMGCs. Developing compounds that inhibit HIF-1α may be a potential approach to FMGC treatment. ? 2020 The Author(s).
Subjects
Feline; Hypoxia-inducible factor 1 alpha (HIF-1α); Mammary gland carcinoma; Vascular endothelial growth factor (VEGF)
SDGs
Other Subjects
hypoxia inducible factor 1alpha; vasculotropin; hypoxia inducible factor 1alpha; vasculotropin; Article; breast carcinoma; cancer staging; cancer therapy; cancer tissue; cat; cell invasion; clinical outcome; controlled study; distant metastasis; female; follow up; gene overexpression; genetic analysis; histology; human; human tissue; immunohistochemistry; lymph node metastasis; male; nonhuman; overall survival; protein expression; tissue microarray; tumor associated leukocyte; tumor invasion; tumor microenvironment; animal; carcinoma; cat disease; experimental mammary neoplasm; gene expression regulation; genetics; metabolism; mortality; pathology; prognosis; retrospective study; veterinary medicine; Animals; Carcinoma; Cat Diseases; Cats; Female; Gene Expression Regulation, Neoplastic; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Mammary Neoplasms, Animal; Prognosis; Retrospective Studies; Vascular Endothelial Growth Factors
Type
journal article