Immunohistochemical detection of P53 and MDM2 and its correlation with histological grading system in ovine pulmonary adenocarcinoma
AbstractOvine pulmonary adenocarcinoma (OPA) is a cancer disease in sheep caused by Jaagsiekte sheep retrovirus (JSRV). The retrovirus is distinctive among viruses for inducing carcinogenesis of lung epithelial cells and cause a lung adenocarcinoma. OPA has numerous characters same as human lung adenocarcinoma, involving a similar histological organization and motivation of most cell signalling pathways. P53 pathway is frequently changed in human lung adenocarcinoma, in specific due to the increase expression of MDM2 and it is the main regulator of P53. Here, we have a go at something new to confirm the possible expression of p53 and MDM2 in OPA as a translational animal model for human lung adenocarcinoma, and to identify the correlation between P53 and MDM2 expression. 1645 of lung samples from different breeds were macroscopically tested. OPA was recognized in 21 samples and further assessed by histology and immunohistochemistry. Histologically, proliferative cancer foci were distributed and contained of cuboidal or columnar cells and arising papillary to acinar patterns. The nuclear expression of P53 and MDM2 was detected in 90% and 95% respectively in the cancer epithelial cells of OPA respectively. Detectable immunoreactivity for P53 was detected in 6 out of 7 grade I, 7 out of 8 grade II, and 6 out of 6 grade III cancers. In reverse with P53, MDM2 was detected in 18 cases with moderate and high expression. In addition, there was statistically relationship between both protein expressions. Our findings suggested that overexpression of MDM2 plays an essential part in OPA carcinogenesis and is dependable on the grading system, and its overexpression can be convinced by P53 expression.
1- Both P53 and MDM2 proteins are overexpressed in the OPA and the overexpression is positively correlated.
2- The level of nuclear expression of P53 and MDM2 is higher in grade III compare to grade I in OPA.
3- P53 and MDM2 play a significate role in the carcinogenesis of lung epithelial cancer cells in sheep.
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