Prognostic significance of PCNA, MMP-9 and p53 in bovine ocular squamous cell carcinomas

Abstract

In this study, we aimed to compare and correlate the PCNA, MMP-9 and p53 expressions and differentiation degree of bovine ocular squamous cell carcinomas (BOSCCs) by immunohistochemical methods. The material of this study was composed of BOSCC biopsy samples taken from 30 cattle brought to our department. Tissue samples were fixed in 10% buffered formalin, processed routinely, embedded in paraffin, sectioned at 5 μm, and stained with hematoxylin & eosin in order to detect histopathological changes. Sections were examined and photographed under a light microscope. Avidin-biotin-peroxidase method was used for immunohistochemistry. Macroscopically the masses were nodular to cauliflower-like shaped. The surfaces of the masses were highly hemorrhagic and ulcerative, and sometimes covered with a purulent discharge. Histopathologically, we defined cases with excessive and large numbers of keratin pearls, large tumoral islands, and evident squamous differentiation as well-differentiated. Cases with smaller tumoral islets, decreased number and size of keratin pearls, but higher number of poorly-differentiated cells compared to well-differentiated cases were defined as moderately-differentiated. Tumors in which keratinization was either absent or formed in individual cells were classified as poorly-differentiated. Statistical analysis revealed that there was no significant difference between well, moderately, and poorly differentiated tumors in terms of PCNA and MMP-9 expressions, but we found that the increase in p53 expression negatively correlated with the degree of differentiation of the tumor. In conclusion, we think that p53 can be a useful marker in determining the prognosis of BOSCCs.

Expression of matrix metalloproteinases (MMPs)−2/-7/-9/-14 and tissue inhibitors of MMPs (TIMPs)−1/-2 in bovine cutaneous fibropapillomas associated with BPV-2 infection

“…In bovine fibropapillomas, our results show for the first time the overexpression of pro-and active forms of MMP-9, which may possess an important proteolytic activity directed to different ECM proteins; by immunohistochemistry, MMP-9 has been detected both in epithelial and fibroblast cells, which may indicate a possible role in cell proliferation and detachment from basement membrane through an intense digestion of ECM proteins. In addition, a similar pattern of MMP-9 expression was described in bovine ocular squamous cell carcinomas, a tumor type attributed to different factors such as papillomavirus and herpesviruses, where an increased MMP-9 expression compared to the control group was demonstrated (36). In a recent in vivo study, Altamura et al (37), showed that in feline oral squamous cell carcinoma cell lines, MMP-2 and−9 are expressed at gene and protein level, which in turn may suggest a contribution of feline oral squamous cell carcinoma cells to invasiveness, in agreement with studies on human oral squamous cell carcinomas, where MMPs expression may play a relevant role in determining the invasive phenotype of tumor cells (38).…”

Comprehensive Network and Structural Analysis of Bovine Papillomavirus, Squamous Cell Carcinoma Markers, and Elucidation of Efficacy Mechanisms of Phytochemicals fromThuja Occidentalis

“…This study expands beyond the viral focus to scrutinize host cellular components associated with BPV-induced squamous cell carcinoma. [13,[18][19][20][21][22] A panel of 24 markers and receptors, including crucial entities such as VEGF-C, EGFR, and TP53, was systematically analyzed to discern their interactions with various BPV variants. The outcomes of this analysis shed light on potential key players in the viral-host interplay, which can help development of targeted therapeutic interventions.…”

“…Notably, the lack of significant interactions for BPV types 8, 10, and 12 with the screened markers suggests distinct characteristics and potential variations in their pathogenic mechanisms. [5,6,18] The analysis of 24 markers/receptors associated with BPV-induced squamous cell carcinoma provides a comprehensive overview of potential molecular targets. The higher affinity interactions observed for VEGF-C, EGFR, PDGFC, PDGFC-alpha, bFGF, GPC1, and FLG across multiple BPV variants indicate the significance of these markers in the context of viral pathogenesis.…”

“…The intriguing aspect of papillomavirus biology lies in its close association with the host epithelial cell's differentiation process. [1][2][3][4][5][6][7] Despite the predominantly benign nature of papillomavirus infections, there are instances where benign warts persist and may progress to squamous cell carcinoma. [5,[7][8][9][10] This progression to malignancy although is reported to be a rare outcome, represents a dead-end process for the virus and host causing severe economic losses to the farmers.…”

“…Bovine Papillomavirus (BPV) infections in cattle have garnered significant attention due to their association with squamous cell carcinoma and other pathological conditions. [1,5,6,12] Understanding the diverse array of BPV variants, their interactions with host cellular components, and exploring potential therapeutic interventions is crucial for advancing our knowledge in veterinary medicine and developing effective strategies to manage these viral infections. In veterinary medicine, certain papillomavirus types have gained prominence for their strong association with malignant neoplasms.…”