Abstract 1536: Tumor heterogeneity and primary versus metastatic evaluation of PD-L1
Authors: Lorenzo Colarossi, Eleonora Aiello, Marie Cumberbatch, Cristina Colarossi, Chris Womack, Lorenzo Memeo
Journal: Cancer Research (2019)

Abstract Immunotherapy with checkpoint inhibitors allowing recovery of effector cell function, has been demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. However, current assays for the prognostic and/or predictive role of tumor PD-L1 expression are not fully standardized with respect to either quantity or distribution of expression, or regarding the concordance of expression in primary tumor versus metastasis. To assess tumor heterogeneity, we evaluated PD-L1 expression using the Ventana SP-263 assay in paired formalin fixed paraffin embedded (FFPE) blocks from the same primary tumor for each of 22 lung squamous cell carcinoma (SCC), 6 lung adenocarcinoma (ADC), 53 gastric ADC, 55 colorectal ADC, 60 urothelial bladder carcinoma, 3 pancreatic ductal ADC and 4 head and neck SCC. In addition, PD-L1 expression in primary tumor and synchronous metastasis was evaluated in 32 cases of lung neoplasm (10 ADC +22 SCC), 30 cases of gastric adenocarcinoma, 55 cases of colorectal adenocarcinoma, and 16 head and neck SCC, each with corresponding synchronous metastases. PD-L1 expression was determined by pathologist evaluation of the percentage of positive tumor cells and cases were grouped into categories representing &amp;lt;1%, 2-9%, 10-25%, 26-49%, 50-75% and 76-100%, with those samples expressing more than 25% tumor positivity considered as expressing “high” PD-L1 levels. In lung carcinoma, just 1 case of SCC exhibited a change in PD-L1 classification when two blocks from the same tumor were evaluated (0% vs 5%), and also for 1 case of ADC (2% vs 0%) . In gastric ADC we recorded a change in classification in 1 out of 53 cases (5% vs 0%), and for CRC ADC we found a difference between the two blocks evaluated in just 1 of the 55 cases (0% vs 50%). For the remaining tumor cohorts (60 bladder carcinoma, 4 head and neck SCC and 3 pancreatic ADC) 100% concordance was observed between two blocks from the same tumor. Evaluation of primary tumors and synchronous metastasis revealed no differences in PD-L1 scores for the 32 cases of lung carcinoma, or for the 16 head and neck SCC cases. In the 30 gastric ADC cases, there was a discordant PD-L1 expression score for just one pair of tumors (primary tumor 3% and metastasis 0%). Similarly, 1 of 55 CRC ADC examined revealed a primary tumor PD-L1 score of 50% while the metastatic tissue was negative. Taken together, these data demonstrate that PD-L1 expression between two sites in the same tumour, and between primary versus synchronous metastases is remarkably consistent. The conclusions drawn are that a representative PD-L1 score may be achieved from a single FFPE tumour block, and that for cases where obtaining tissue from a primary tumor may be challenging, PD-L1 could be evaluated in metastatic tissue. Citation Format: Lorenzo Colarossi, Eleonora Aiello, Marie Cumberbatch, Cristina Colarossi, Chris Womack, Lorenzo Memeo. Tumor heterogeneity and primary versus metastatic evaluation of PD-L1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1536.