Prognostic Value of p16 Protein in Patients With Surgically Treated Non-small Cell Lung Cancer; Relationship With Ki-67 and PD-L1

Abstract

Background/Aim: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death. Patients eligible for surgery have better overall survival rate than patients who are not eligible. We investigated the prognostic value of p16 in patients who underwent surgery for lung cancer, in association with other factors such as PD-L1 and Ki-67. Materials and Methods: Expression of p16 was evaluated along with the presence of Ki-67 and PD-L1 in 256 NSCLC patients treated only surgically. Results: Adenocarcinoma was the prevalent histotype (56%) followed by squamous cell (29%) and differentiation grade of 3 was the most common (60%). p16 was detected in 83 patients (30%): low positivity (<10% cells) was observed in 30 samples (11%) and high positivity (>10 % cells) in 53 patients (20%). Ki-67 was detected in 89 patients (34%) with mild positivity in 46 patients (10-25% cells), moderate positivity (26-75% cells) in 30 patients (11%), and high positivity (>75% cells) in 13 patients (5%). An influence of p16 expression (p<0.05) along with grading and staging on overall survival (OS) was found. The average OS was 36 months, but the OS increased up to 54 months when patients were stratified according to p16 expression levels. The stratification by staging showed a significant prognostic value for p16 at an early stage (p<0.014). Conclusion: p16 significantly influences prognosis, notably at an early stage, along with other variables such as grading and staging.

S100A4 Is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma

“…Regarding the value of S100A4 compared to other known prognostic markers such as p16 and PD-L1, we previously showed a decreased relative expression of Cdkn2a (p16) in neoplastic relative to preneoplastic rat cell lines and in human MM cell lines relative to normal mesothelial cells [18]. Interestingly, our findings on MM were consistent with the data of Pezzuto et al, who found altered expression of p16 in patients with NSCLC, indicating that p16 could be a potential marker of lung cancer evolution and aggressiveness, unlike PD-L1 and Ki-67 which did not affect overall survival [47]. Other findings by Chapel et al in a cohort of patients with malignant pleural mesothelioma confirmed that tumor PD-L1 expression was not significantly associated with overall survival [48].…”

Prognostic value of programmed cell death ligand‑1 expression in the tumor‑infiltrating immune cells of patients with lung cancer: A meta‑analysis

“…The overall pooled result showed that PD-L1 expression in TIICs was not associated with OS or DFS in any of the included populations with lung cancer. This finding is consistent with a meta-analysis of the included cancer types ( 30 ), and with the results reported in tumors of the digestive system ( 6 ), as well as cohort studies ( 31 , 32 ). However, the present result contradicts previous studies that revealed that PD-L1 TIIC in primary breast cancer ( 26 ) was associated with improved OS, while in SCLC ( 33 ) and in head and neck cancer ( 34 ) it was associated with longer DFS.…”

Expression and role of p16 and GLUT1 in malignant diseases and lung cancer: A review

“…p16 as a tumor suppressor gene has been shown to interact with P53 increasing the action of cell cycle regulation 30 . The observation that p16 gene preferentially undergoes gene silencing through promoter hypermethylation is of crucial importance in the evidence of protein expression in NSCLC 31 …”

“…30 The observation that p16 gene preferentially undergoes gene silencing through promoter hypermethylation is of crucial importance in the evidence of protein expression in NSCLC. 31…”