p53, Pirh2, and L1CAM as Promising Prognostic Biomarkers of Endometrial Carcinoma: An Immunohistochemical and Genetic Study

Abstract

Endometrial cancer (EC) is the most common gynecologic cancer and the current methods for the prediction of its prognosis and treatment response are unfortunately suboptimal. In this study, we evaluated the prognostic value of p53, Pirh2, and L1CAM in 60 cases of EC using immunohistochemistry (IHC) and polymerase chain reaction. TP53 missense mutations result in nuclear accumulation of p53 protein that can be detected as overexpression by IHC. This is in the form of diffuse strong nuclear positivity involving at least at least >50% of the tumor cells as a whole or if >50% of the tumor cells of a discrete geographical areas. Abnormal p53 IHC expression was expressed in 33.3% of the cases and significantly associated with the tumor grade, myometrial invasion (MI), lymphovascular invasion (LVSI), nodal metastasis, and FIGO stage, and the advanced European Society for Medical Oncology (ESMO) risk groups (P<0.001 for each). High IHC Pirh2 expression was noted in 58.3% of the cases, and significantly associated with MI, LVSI, nodal metastasis, FIGO stage, and high-risk group (P<0.001, P=0.011, P=0.010, P=0.024, P=0.005, respectively). There was a significant upregulation of Pirh2 mRNA expression in EC specimens as compared with the control adjacent tissues (P=0.001). Upregulated Pirh2 mRNA expression had a significant association with Pirh2 immunostaining, tumor grade, tumor stage, MI, lymph node involvement, LVSI, and relapse (P<0.001 for each). Positive L1CAM immunoexpression was noted in 26.7% and was significantly associated with grade, MI, LVSI, nodal metastasis, FIGO stage, and high-risk group (P=0.003, P=0.023, P=0.003, P<0.001, P<0.001, P=0.002, respectively). Analysis of follow-up period revealed that EC with abnormal p53 IHC expression, high pirh2 and positive L1CAM expression exhibited a potent relation with tumor relapse, shorter overall survival and disease-specific survival (P<0.001 for each). Mutant p53, high Pirh2, and L1CAM-positive EC are highly aggressive tumors with a shortened survival rate, dismal outcome, and high risk of relapse after the standard protocol of therapy.

Clinical significance of L1CAM expression and its biological role in the progression of oral squamous cell carcinoma

“…This may be due to difference in the scoring method of immunohistochemical staining. Adnan et al (27) scored by multiplying the intensity of staining with the percentage of positive cells, whereas a cutoff (10% of tumor cells) was used in the present study as it was used in most studies of endometrial carcinoma in which the prognostic value of L1CAM has been well established (12,28,29). Although Adnan et al (27) reported that L1CAM had no effect on either OS or disease-free survival in OSCC, our survival data from 10 years of follow-up showed significantly reduced OS in patients with positive L1CAM (P=0.014).…”

Integrated network pharmacology and phosphoproteomic analyses of Baichanting in Parkinson's disease model mice

“…L1 cell adhesion molecule (L1CAM) is predominantly expressed in neuronal cells and plays an important role in neuronal migration, axon growth, fasciculation and lengthening in nervous system development [ 39 ]. When the phosphorylation of L1CAM protein is abnormal, the phosphorylation of PAK protein is hindered through the NRP1→Rac pathway, and the cells are hypoxic due to abnormal mitochondrial function and insufficient energy supply, which directly or indirectly activate autophagy and apoptosis-related proteins, such as P53 protein, AMPK protein, and mTOR protein, and induce apoptosis [ 40 , 41 ].…”

The value of multimodal functional magnetic resonance imaging in differentiating p53abn from p53wt endometrial carcinoma

“…L1CAM-positive ECs may be more active in mitotic activity. Thus, L1CAM expression is most common in p53abn-type ECs (34). Moreover, Vermij et al (35) showed that the expression level of human epidermal growth factor receptor-2 (Her-2) is highly correlated with p53abn-type EC, and the overexpression of Her-2 can cause abnormality in EC cell proliferation.…”