PD-L1 gene amplification and focality: relationship with protein expression.

PD-L1 (CD274) amplification occurs in a small subset of malignancies and may predict anti-PD-1/PD-L1 immunotherapy responsiveness. We hypothesized that both copy number (CN) and focality of cancer-related PD-L1 amplifications impact protein expression, and, thus, analyzed solid tumors that underwent comprehensive genomic profiling between March 2016 and February 2022 at Foundation Medicine. PD-L1 CN alterations were detected using a comparative genomic hybridization-like method. PD-L1 CN changes were correlated with PD-L1 protein expression (DAKO 22C3 antibody) by immunohistochemistry (IHC). Overall, 60,793 samples were analyzed (most frequent histologies: lung adenocarcinoma (20%), colon adenocarcinoma (12%), lung squamous carcinoma (8%)). Using a definition of CD274 CN ≥ specimen ploidy +4 (6 copies), 1.21% of tumors (738/60,793) were PD-L1 amplified. Focality category distribution was as follows: <0.1 mB (n=18 (2.4%)), ≥0.1 to <4 mB (n=230 (31.1%)), ≥4 to <20 mB (n=310 (42%)), ≥20mB (n=180 (24.4%)). Lower levels of PD-L1 amplification (below specimen ploidy +4) were more frequently non-focal amplifications compared to higher levels. In addition, more focal amplification (<0.1 mB) correlated with higher PD-L1 IHC expression. Median tumor proportion score (TPS) for samples with PD-L1 amplification (ploidy ≥+4) according to focality were 87.5% (<0.1 mB), 80% (≥0.1 to <4 mB), 40% (≥4 to <20 mB), 1% (≥20mB). In specimens with PD-L1 ploidy less than +4, but highly focal (<0.1 mB), the 75th percentile of PD-L1 expression by TPS was 80%. Conversely, non-focal (≥20 mB) PD-L1 amplification (ploidy ≥+4) can present high PD-L1 expression (TPS≥50%), albeit infrequently (0.09% of our cohort). In conclusion, PD-L1 expression measured by IHC is influenced by PD-L1 amplification level and focality. Further correlation between amplification, focality, protein expression and therapeutic outcome for PD-L1 and other targetable genes warrants exploration.

Brachial plexus anesthesia: A review of the relevant anatomy, complications, and anatomical variations.

The trend towards regional anesthesia began in the late 1800s when William Halsted and Richard Hall experimented with cocaine as a local anesthetic for upper and lower limb procedures. Regional anesthesia of the upper limb can be achieved by blocking the brachial plexus at varying stages along the course of the trunks, divisions, cords and terminal branches. The four most common techniques used in the clinical setting are the interscalene block, the supraclavicular block, the infraclavicular block, and the axillary block. Each approach has its own unique set of advantages and indications for use. The supraclavicular block is most effective for anesthesia of the mid-humerus and below. Infraclavicular blocks are useful for procedures requiring continuous anesthesia. Axillary blocks provide effective anesthesia distal to the elbow, and interscalene blocks are best suited for the shoulder and proximal upper limb. The two most common methods for localizing the appropriate nerves for brachial plexus blocks are nerve stimulation and ultrasound guidance. Recent literature on brachial plexus blocks has largely focused on these two techniques to determine which method has greater efficacy. Ultrasound guidance has allowed the operator to visualize the needle position within the musculature and has proven especially useful in patients with anatomical variations. The aim of this study is to provide a review of the literature on the different approaches to brachial plexus blocks, including the indications, techniques, and relevant anatomical variations associated with the nerves involved.