Immunohistochemical Assessment of the P53 Protein as a Predictor of Non-Small Cell Lung Cancer Response to Immunotherapy.

BACKGROUND: Determining predictive biomarkers for immune checkpoint inhibitors (ICIs) is a current challenge in oncology. Previous studies on non-small cell lung cancer (NSCLC) have shown how TP53 gene mutations are correlated with different responses to ICIs. Strong and diffuse immuno-expression of p53 by immunohistochemistry (IHC) is interpreted as a likely indicator of a TP53 gene mutation. We aimed to assess the p53 protein expression via IHC in NSCLC as a predictive biomarker of the response to ICIs. METHODS: This was a retrospective hospital-based study of patients with NSCLC treated with Nivolumab in the University Hospital of Salamanca. All diagnostic biopsies were studied via IHC (measuring p53 protein expression, peroxidase anti-peroxidase immunohistochemistry technique using Leica BOND Polymer development kits). Survival analysis was performed by subgroups of expression of p53 and other factors using the Kaplan-Meier estimator and Cox proportional-hazards model. RESULTS: Seventy-three patients were included (59 men and 14 women). The median age was 68 (44-84) years. Thirty-six biopsies were adenocarcinoma, 34 were squamous, and three were undifferentiated. In 41 biopsies (56.2%), the cellular expression of p53 was <5% (Group A), and in 32 biopsies (43.8%), the expression was ≥5% (Group B). In the general analysis, no differences were observed in overall survival (OS) (A: 12 months vs B: 20 months; p = 0.070) or progression-free survival (PFS) (A: 4 m vs B: 7 m; p = 0.064). Significant differences were observed in adenocarcinomas for both OS (A: 8 m vs B: median not reached; p = 0.002) and PFS (A: 3 m vs 8 m; p = 0.013). No differences in PFS and OS were observed in squamous cell carcinoma. Significant differences were observed in OS in the PD-L1 negative group (0% expression) (A: 13 m vs B: 39 m; p = 0.024), but not in PFS (A: 3 m vs B: 7 m; p = 0.70). No differences were observed in the PD-L1 positive group. CONCLUSIONS: A trend toward a greater response to ICIs was observed in the PFS and OS of patients with high expression of p53 by IHC (TP53 mutation), especially in the PD-L1 negative adenocarcinoma subgroup. These results will make it possible to make future modifications to the clinical guidelines of NSCLC according to the expression of p53.

Liquid Biopsy as Novel Tool in Precision Medicine: Origins, Properties, Identification and Clinical Perspective of Cancer's Biomarkers.

In recent years, there has been an increase in knowledge of cancer, accompanied by a technological development that gives rise to medical oncology. An instrument that allows the implementation of individualized therapeutic strategies is the liquid biopsy. Currently, it is the most innovative methodology in medical oncology. Its high potential as a tool for screening and early detection, the possibility of assessing the patient's condition after diagnosis and relapse, as well as the effectiveness of real-time treatments in different types of cancer. Liquid biopsy is capable of overcoming the limitations of tissue biopsies. The elements that compose the liquid biopsy are circulating tumor cells, circulating tumor nucleic acids, free of cells or contained in exosomes, microvesicle and platelets. Liquid biopsy studies are performed on various biofluids extracted in a non-invasive way, and they can be performed both from the blood and in urine, saliva or cerebrospinal fluid. The development of genotyping techniques, using the elements that make up liquid biopsy, make it possible to detect mutations, intertumoral and intratumoral heterogeneity, and provide molecular information on cancer for application in medical oncology in an individualized way in different types of tumors. Therefore, liquid biopsy has the potential to change the way medical oncology could predict the course of the disease.