Background: Programmed death-ligand 1 (PD-L1) is a crucial biomarker predicting efficacious treatment of immune checkpoint inhibitors (ICIs). Understanding the genetic association of PD-L1 expression provides insights into the tumor-immune interaction and further exploration of immunotherapeutic biomarkers. However, the diverse and dissimilar quantifying assays might lead to inconsonant and confusing results, not conducive to the following research. Previous studies identified distinct staining utility among multiple PD-L1 antibodies, however, whether the genomic correlate of stained PD-L1 is also impacted by different testing assays is largely unknown.Methods: We evaluated 873 Chinese LUAD patients with lung adenocarcinoma in whom FDA-approved PD-L1 testing (22C3, Dako, Glostrup, Denmark; SP263, Ventana, Tucson, AZ) and targeted next-generation sequencing (3D Medicines Inc.) was performed on the same tissue. Data from Memorial Sloan Kettering Cancer Center (MSKCC), The Cancer Genome Atlas (TCGA) and the OAK trial were analyzed for further validation.Results: In the 3DMed database (n¼873), PD-L1 expression in tumor cells was positively correlated with tumor mutational burden. (p<0.001). PD-L1 positivity was more common in metastatic lymph nodes compared to primary lung tumors and other metastatic samples (p ¼0.009). Deleterious mutations in KRAS, TP53, ALK and MET significantly associated with PD-L1 high expression (each p<0.05) and EGFR and ERBB2 mutations associated with PD-L1 negativity (each p<0.05). Comparing the results in the 3DMed, MSKCC, TCGA, and OAK cohorts using different methods to quantifying PD-L1 expression, most of the positive results were validated in at least two cohorts, except ERBB2.
The COVID-19 pandemic presented numerous challenges to the continuity of programmed cell death ligand 1 (PD-L1) assay training events conducted by our organization. Under typical conditions, these training events are face-to-face affairs, where participants are trained to assay algorithms on glass slides during multi-headed scope sessions. Social distancing measures undertaken to slow pandemic spread necessitated the adaptation of our training methods to facilitate assay training and subsequent continuation of clinical trials. The present report details the creation and use of the Roche pathology training portal (PTP) that allowed for remote training to diagnostic assay algorithms. The PTP is a web-based system comprised of a learning management system (LMS) coupled to an image management system (IMS). Whole slide images (WSIs) were produced using a DP200 instrument (Roche, Pleasanton, CA) and these scan files were then uploaded to an IMS. Courses were created on the LMS using annotated WSIs that were shared with enrolled pathologists worldwide during assay training events. These courses culminated in assay certification examinations, where pathologists evaluated test-case WSIs and evaluated these cases within the LMS. Trainee submissions were analyzed for pass/fail status by comparing user data entries with consensus scores on these test-case WSIs. To date, 47 pathologist trainings have occurred and of these, 44 have successfully passed the associated assay certification exam on the first attempt (93% 1 st -try pass rate). The PTP allowed roche to continue training sites during the COVID-19 pandemic, and these early results demonstrate the capability of this digital solution regarding PD-L1 diagnostic assay training events.
fourths of an inch from the apex, is a foul, sloughy-looking ulcer, with ragged, everted edges, and an indurated base. The tongue is thickly coated, and articulation and deglutition are difficult. Tho growth is two and one-half inches in length, by one inch in breadth. Patient states that, about fourteen years ago, a small kernel appeared on the left side of the tongue, a short distance from the apex ; this has gradually spread downwards and backwards, producing abundant salivation, and at times causing severe pain. Tho submaxillary glands aro not affected. On the 21th, ho was etherized ; during the process of etherization, the pulse and the respiration suddenly ceased, without any apparent causo, and for a few seconds the patient's condition was quite alarming ; soon, however, pulsation was felt again at tho wrist, at first slowly, and thon gradually rising from 30 beats a minute to 40, 50, and, finally, to 80 ; respiratory action recommenced, and there was no further trouble. An incision, about three inches long, was made, from a point over tho lesser cornu of the hyoid bone, toward the left mastoid process ; the left lingual artery was found beneath the triangle formed by the hypoglossal nerve and tho tendon of the digastricus, and tied. Tho growth was then cut out with scissors, and a margin of a quarter of an inch of sound tissue was removed with it. There was almost no bleeding. Dr. Fitz was kind enough to examine tho tumor, microscopically, and reported that it ' was an epitholioma. The wounds in the neck and mouth soon healed ; tho ligature came away from tho lingual artery on or about the tenth day, and on the first of April the patient left tho hospital, perfectly well. Ligature of tho lingual artery in connection with operations on the tongue is not a new proceeding ; it has been abandoned, I suppose, on account of the troublesome dissection required to secure tho artery. The wound is, at the end of tho operation, a pretty deep one, and tho movements of tho larynx and hyoid bone embarrass the operator. As the lingual arteries, according to llyrtl, do not, anastomose, it is easy to see how completely the supply of blood may be cut off from tho side of tho tongue corresponding to tho ligatured artery. This is tho second case that I have treated in this way, and I have been well pleased with the results.Mrs. 0., light mulatto, oet. 59, admitted into Aged Colored Women's Home in January, 1872. Had always been a healthy woman. Father was said to havo died of cancer of stomach. Mother said to have died of swelling of the bowels. Had had one child. Menstruation stopped at tho age of 45 years. Had during that winter more or less trouble connected with the cessation of menstruation ; enjoying then good health until tho following winter, when she was again unable to work, owing to tho severe pains which she suffered in chest and bowels.After this, was in excellent health, and worked hard for twelve years.In June, 18GY, sho asserts that sho felt something give way in right groin, while lifting ; was taken unwe...
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