The advent of molecular medicine has transformed breast cancer management. Breast cancer is now recognised as a heterogenous disease with varied morphology, molecular features, tumour behaviour, and response to therapeutic strategies. These parameters are underpinned by a combination of genomic and immunohistochemical tumour factors, with estrogen receptor (ER) status, progesterone receptor (PgR) status, human epidermal growth factor receptor-2 (HER2) status, Ki-67 proliferation indices, and multigene panels all playing a contributive role in the substratification, prognostication and personalization of treatment modalities for each case. The expression of Ki-67 is strongly linked to tumour cell proliferation and growth and is routinely evaluated as a proliferation marker. This review will discuss the clinical utility, current pitfalls, and promising strategies to augment Ki-67 proliferation indices in future breast oncology.

/pdf/ki-67-as-a-prognostic-biomarker-in-invasive-breast-cancer-3yu7t1pup5.pdf

Ki-67 as a Prognostic Biomarker in Invasive Breast Cancer

EZH2 regulates PD-L1 expression via HIF-1α in non-small cell lung cancer cells.

To determine the prognostic value of programmed death-ligand 1 (PD-L1) score in early-stage epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), contrasted against EGFR-wildtype NSCLC.Consecutive patients with Stage IA-IIIA NSCLC diagnosed 1st January 2010-31st December 2019 at National Cancer Centre Singapore with evaluable EGFR and PD-L1 status were included. Co-primary end-points were 2-year disease-free survival (DFS) and 5-year overall survival (OS) by Kaplan-Meier method.455 patients were included (267 EGFR-mutated, EGFR-M+; 188 EGFR-wildtype, wt). Median age at diagnosis was 65 years, 52.3% (238/455) of patients were males, 62.9% (286/455) of patients were never-smokers and 92.5% (421/455) of patients had R0 resection. Stage IA comprised 42.4% (193/455) of patients, Stage IB comprised 23.1% (105/455) of patients, Stage IIA comprised 10.8% of patients (49/455), Stage IIB comprised 5.1% of patients (23/455) and Stage IIIA comprised 18.7% (85/455) of patients. Among EGFR-M+, 45.3% (121/267) were Ex19del and 41.9% (112/267) were L858R. PD-L1 ≥1% among EGFR-M+ and EGFR-wt was 45.3% (121/267) and 54.8% (103/188) respectively (p = 0.047). At median follow-up of 47 months, 178 patients had relapsed. Among EGFR-M+, 2-year DFS comparing PD-L1 <1% and PD-L1 ≥1% was 78.1% and 67.6% (p = 0.007) while 5-year OS was 59.5% and 42.8% (p = 0.001), respectively. Controlling for age, gender, lymphovascular invasion, adjuvant therapy and resection margin status, PD-L1 ≥1% (hazard ratio, HR 2.18, 95% CI 1.04-4.54, p = 0.038), stage IIB (HR 7.78, 95% CI 1.72-35.27, p = 0.008) and stage IIIA (HR 4.45, 95% CI 1.44-13.80, p = 0.01) emerged as independent predictors of inferior OS on multivariable analysis. In exploratory analysis, genomic analysis of 81 EGFR-M+ tumours was performed. PD-L1 ≥1% tumours had significantly higher rates of TP53 mutations (36.1% versus 15.6%, p = 0.04), with predominantly missense mutations.PD-L1 ≥1% is an independent predictor of worse OS among early-stage EGFR-mutated NSCLC and is associated with inferior DFS regardless of EGFR status. PD-L1 score as a risk stratification factor should be evaluated in prospective adjuvant studies among EGFR-mutated NSCLC. 

PD-L1 score as a prognostic biomarker in asian early-stage epidermal growth factor receptor-mutated lung cancer.

Expression of PD-L1, cancer stem cell and epithelial-mesenchymal transition phenotype in non-small cell lung cancer.

OBJECTIVES Conflicting results have been reported about the prognostic value of programmed death ligand 1 (PD-L1) protein and gene expression in lung adenocarcinoma METHODS We performed a comprehensive online search to explore the association between PD-L1 expression (protein and messenger RNA) and overall survival (OS) or disease-free survival Outcomes also included pooled rates of high PD-L1 protein expression in different cell types, per threshold used and per antibody used A pooled gene expression analysis was also performed on 3 transcriptomic data sets that were obtained from The Cancer Genome Atlas database and the Gene Expression Omnibus database RESULTS A total of 6488 patients from 25 studies were included The pooled results suggested that high PD-L1 expression was associated with shorter OS [hazard ratio (HR) 157; P < 0001] and disease-free survival (HR 1341; P = 0037) in the overall population The overall pooled rate of high PD-L1 protein expression was 29% (95% confidence interval 23-34%) in tumour cells In subgroup analysis, high PD-L1 protein expression in tumour cells predicted worse OS and disease-free survival A pooled analysis of The Cancer Genome Atlas and Gene Expression Omnibus data sets revealed that higher levels of PD-L1 messenger RNA predicted poorer OS in the entire population CONCLUSIONS This study is, to our knowledge, the largest pooled analysis on the subject to shed light on the high expression rate of PD-L1 and the prognostic value of high PD-L1 expression in resected lung adenocarcinomas PD-L1 gene expression is a promising prognostic factor for patients with surgically resected lung adenocarcinoma Standardization of staining should be underscored prior to routine implementation

Prognostic implications of programmed death ligand 1 expression in resected lung adenocarcinoma: a systematic review and meta-analysis

Background: The prognostic role of PD-L1 expression in surgically resected lung adenocarcinoma (ADC) remains controversial The present study was aimed to clarify the role of PD-L1 expression in predicting prognosis and to investigate its biological function in ADC

Materials and Methods: The association between PD-L1 expression and clinical outcomes in patients with resected ADC was analyzed using immunohistochemistry (IHC) in our cohort (n=104), externally validated by a meta-analysis of 13 published studies The biological role of PD-L1 in ADC was explored using gene set enrichment analysis (GSEA)

Results: Positive PD-L1 expression in tumor cells was observed in 385% (40/104) High PD-L1 expression levels were significantly correlated with poor overall survival (P=0008) Furthermore, the meta-analysis also showed that positive PD-L1 expression was associated with shorter OS than negative PD-L1 expression (HR= 175, 95% CI: 126-242; P<0001) In subgroup analysis stratified according to ethnicity, the pooled results demonstrated that increased PD-L1 expression was an unfavorable prognostic factor for Asian populations (HR= 211, 95% CI: 148-302; P<0001), but not for non-Asian populations (HR=116, 95% CI: 063-211, P=064) The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with positive lymph node metastasis (OR=174, 95% CI: 123-246; P=0002) and male (OR=156, 95% CI: 102-237; P=004) GSEA revealed PD-L1 expression levels positively correlated with immune process or immune-related pathways

Conclusion: PD-L1 expression is an important negative prognostic factor in resected ADC This finding has important implications for immunotherapy targeting the PD-1/PD-L1 pathway in patients with resected ADC

/pdf/prognostic-value-of-pd-l1-expression-in-resected-lung-1nbjzlxt4y.pdf

Prognostic value of PD-L1 expression in resected lung adenocarcinoma and potential molecular mechanisms.

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Prognostic value of PD-L1 expression in resected lung adenocarcinoma and potential molecular mechanisms.