PD-L1 expression heterogeneity in non-small cell lung cancer: evaluation of small biopsies reliability
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Enrico Munari1,2, Giuseppe Zamboni1, Marcella Marconi1, Marco Sommaggio1, Matteo Brunelli2, Guido Martignoni2,3, George J. Netto4, Francesca Moretta5, Maria Cristina Mingari6, Matteo Salgarello7, Alberto Terzi8, Vincenzo Picece9, Carlo Pomari10, Gianluigi Lunardi9, Alberto Cavazza11, Giulio Rossi12, Lorenzo Moretta13 and Giuseppe Bogina1
1Department of Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Italy
2Department of Pathology AOUI, University of Verona, Verona, Italy
3Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Italy
4Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA
5Department of Laboratory Medicine, Sacro Cuore Don Calabria Hospital, Negrar, Italy
6Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy
7Department of Nuclear Medicine, Sacro Cuore Don Calabria Hospital, Negrar, Italy
8Department of Thoracic Surgery, Sacro Cuore Don Calabria Hospital, Negrar, Italy
9Department of Oncology, Sacro Cuore Don Calabria Hospital, Negrar, Italy
10Department of Pulmonology, Sacro Cuore Don Calabria Hospital, Negrar, Italy
11Department of Pathology, Arcispedale S. Maria Nuova/IRCCS, Reggio Emilia, Italy
12Department of Pathology, Azienda USL Valle d'Aosta, Aosta, Italy
13Immunology Research Area, IRCCS Bambino Gesu Pediatric Hospital, Rome, Italy
Enrico Munari, email: [email protected]
Keywords: PD-L1, lung cancer, immunotherapy, SP263, pembrolizumab
Received: July 12, 2017 Accepted: August 27, 2017 Published: October 04, 2017
Immunotherapy with checkpoint inhibitors, allowing recovery of effector cells function, has demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. Recently, the anti-PD1 agent pembrolizumab was granted FDA approval for the first line treatment of patients with advanced non–small cell lung cancer (NSCLC) whose tumors show PD-L1 expression in ≥ 50% of neoplastic cells and as a second line treatment for patients with NSCLC expressing PD-L1 in ≥1% of neoplastic cells, evaluated with a validated assay. For the large majority of patients such evaluation is made on small biopsies. However, small tissue samples such as core biopsies might not be representative of tumors and may show divergent results given the possible heterogeneous immunoexpression of the biomarker. We therefore sought to evaluate PD-L1 expression concordance in a cohort of 239 patients using tissue microarrays (TMA) as surrogates of biopsies stained with a validated PD-L1 immunohistochemical assay (SP263) and report the degree of discordance among tissue cores in order to understand how such heterogeneity could affect decisions regarding therapy.
We observed a discordance rate of 20% and 7.9% and a Cohen’s κ value of 0.53 (moderate) and 0,48 (moderate) for ≥ 1% and ≥ 50% cutoffs, respectively.
Our results suggest that caution must be taken when evaluating single biopsies from patients with advanced NSCLC eligible for immunotherapy; moreover, at least 4 biopsies are necessary in order to minimize the risk of tumor misclassification.
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