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Background: The clinical significance of tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression has been thoroughly researched in squamous cell carcinoma of the head and neck (SCCHN). To address the impact of intra- and intertumoral heterogeneity in these biomarkers, we explored the concordance of PD-L1 combined positive score (CPS) and stromal TILs in different paired tissue sample types, while evaluating their internal relationship and prognostic impact. Methods: A total of 165 tissue blocks from 80 SCCHN patients were reviewed for TILs and PD-L1 CPS. Concordance between paired tissue samples was evaluated, and their association with several clinicopathological variables, overall survival (OS), and disease-free survival (DFS) was determined. Results: Biopsies and paired resection material were severely discordant in 39% and 34% of samples for CPS and TIL count, respectively, of which CPS was underscored in 27% of biopsies. In paired primary tumor–metastatic lesions, the disagreement was lower for CPS (19%) but not for TIL count (44%). PD-L1 CPS was correlated with prolonged OS when calculated from tissue acquirement, while extended OS and DFS were observed for high TIL density. Conclusion: Intertumoral and, especially, intratumoral heterogeneity were confounding factors when determining PD-L1 CPS and TIL count on paired tissue samples, indicating the increasing necessity of assessing both biomarkers on representative tissue material. Although TILs hold valuable prognostic information in SCCHN, the robustness of PD-L1 as a biomarker in SCCHN remains ambiguous.

Diagnosis of lung cancer requires histological examination of a tissue sample, which in turn requires an invasive procedure that cannot always be obtained. Circulating tumor DNA can be reliably detected in blood samples of advanced-stage lung cancer patients and might also be a minimally invasive alternative for early-stage lung cancer detection. We wanted to explore the potential of targeted deep sequencing as a test for the diagnosis of early-stage lung cancer in combination with imaging. Mutation detection on cell-free DNA from pretreatment plasma samples of 51 patients with operable non-small cell lung cancer was performed and results were compared with 12 control patients undergoing surgery for a non-malignant lung lesion. By using a variant allele frequency threshold of 1%, somatic variants were detected in 23.5% of patients with a median variant allele fraction of 3.65%. By using this threshold, we could almost perfectly discriminate early-stage lung cancer patients from controls. Our study results are discussed in the light of those from other studies. Notwithstanding the potential of today's techniques for the use of liquid biopsy-based cell-free DNA analysis, sensitivity of this application for early-stage lung cancer detection is currently limited by a biological background of somatic variants with low variant allele fraction. ispartof: CANCERS vol:14 issue:8 ispartof: location:Switzerland status: published

Case report of malignant pleural mesothelioma with an ALK gene rearrangement, detected by FISH and confirmed by RNA-based next-generation sequencing. The co-occurrence of ALK gene fusions with the more common genetic alterations in CDKN2A, NF2 and BAP1 has, to our best knowledge, not yet been described in malignant mesothelioma. Furthermore, this unexpected finding could suggest a potential target for therapy in this subset of malignant mesotheliomas. ispartof: PATHOLOGY RESEARCH AND PRACTICE vol:231 ispartof: location:Germany status: published