RESUMO
OBJECTIVES: Tumor programmed death ligand 1 (PD-L1) expression is associated with improved clinical benefit from immunotherapies targeting the PD-1 pathway. We conducted a global, multicenter, retrospective observational study to determine real-world prevalence of tumor PD-L1 expression in patients with NSCLC. MATERIALS AND METHODS: Patients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤5 years old) obtained before treatment were identified in 45 centers across 18 countries. Tumor samples from eligible patients were selected consecutively, when possible. PD-L1 expression was evaluated at each center using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). RESULTS: Of 2617 patients who met inclusion criteria, 2368 (90%) had PD-L1 data; 530 (22%) patients had PD-L1 TPSâ¯≥â¯50%, 1232 (52%) had PD-L1 TPSâ¯≥â¯1%, and 1136 (48%) had PD-L1 TPSâ¯<â¯1%. The most common reason for not having PD-L1 data (nâ¯=â¯249) was insufficient tumor cells (<100) on the slide (nâ¯=â¯170 [6%]). Percentages of patients with PD-L1 TPSâ¯≥â¯50% and TPSâ¯≥â¯1%, respectively were: 22%/52% in Europe; 22%/53% in Asia Pacific; 21%/47% in the Americas, and 24%/55% in other countries. Prevalence of EGFR mutations (19%) and ALK alterations (3%) was consistent with prior reports from metastatic NSCLC studies. Among 1064 patients negative for both EGFR mutation and ALK alteration, the percentage with PD-L1 TPSâ¯≥â¯50% and TPSâ¯≥â¯1%, respectively, were 27% and 53%. CONCLUSIONS: This is the largest real-world study in advanced NSCLC to date evaluating PD-L1 tumor expression using the 22C3 pharmDx kit. Testing failure rate was low with local evaluation of PD-L1 TPS across a large number of centers. Prevalence of PD-L1 TPSâ¯≥â¯50% and TPSâ¯≥â¯1% among patients with stage IIIB/IV NSCLC was similar across geographic regions and broadly consistent with central testing results from clinical trial screening populations.
Assuntos
Antígeno B7-H1/genética , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Expressão Gênica , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prevalência , Estudos RetrospectivosRESUMO
INTRODUCTION: Somatostatin receptors are expressed in a large number of human tumours. The somatostatin receptors types 1-5 expression in a series including 100 gastro-entero-pancreatic endocrine tumours were analysed. METHODS: From a prospectively built database of patients with gastro-entero-pancreatic endocrine tumours referred from three institutions, 100 cases with clinical and pathological data were selected. Somatostatin receptors expression by immunohistochemistry with somatostatin receptor types 1-5 antibodies in tissue paraffin sections were studied and correlated with the histological diagnosis according to the WHO classification, location and functional status. RESULTS: Of the 100 cases, 67 were gastrointestinal tumours, 25 pancreatic and 8 liver metastasis of unknown origin. Thirty-one of them were functioning tumours: 2 insulinomas, 5 gastrinomas, 1 glucagonoma and 23 carcinoids. Somatostatin receptors expression was observed in 94 tumours. The six negative cases were all non-functioning tumours. Somatostatin receptors 2a and 5 were highly expressed (86 and 62%, respectively), and surprisingly found even in poorly differentiated endocrine carcinomas. Somatostatin receptors expression was less frequent in pancreatic than in gastrointestinal tumours. Well-differentiated neoplasms had a higher density of somatostatin receptors. Only SSTR2a showed membrane staining. CONCLUSIONS: Immunohistochemistry revealed that somatostatin receptors were highly expressed in both primary and metastatic gastro-entero-pancreatic endocrine tumours with heterogeneous staining distribution. It proved to be a reliable technique even in small tumour samples.