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Background: Predictive biomarker testing has a key role in the treatment decision-making for patients with non-small cell lung cancer (NSCLC) and is mandated by (inter)national guidelines. The aim of this study was to establish guideline-adherent biomarker testing rates in the Netherlands in 2019 and to examine associations of demographical, clinical, and environmental factors with guideline-adherent testing., Methods: This study involved the integration of clinical data of the Netherlands Cancer Registry with pathology reports of the Dutch Nationwide Pathology Databank. Data extracted from these reports included sample type, diagnosis, and molecular testing status of predictive biomarkers. The study population comprised all patients diagnosed with metastatic non-squamous NSCLC in the Netherlands in 2019., Results: In the cohort of 3877 patients with metastatic non-squamous NSCLC under investigation, overall molecular testing rates for non-fusion predictive biomarkers (EGFR, KRAS, BRAF, ERBB2, MET) ranged from 73.9 to 89.0 %, while molecular testing for fusion-drivers (ALK, ROS1, RET, NTRK) ranged from 12.6 % to 63.9 %. Guideline-adherent testing of EGFR, KRAS, and ALK was performed in 85.2 % of patients, with regional rates spanning from 76.0 % to 90.8 %. Demographical and clinical factors associated with guideline-adherent biomarker testing included lower age (OR = 1.05 per one year decrease; p < 0.001), female sex (OR = 1.36; p = 0.002), diagnosis of adenocarcinoma (OR = 2.48; p < 0.001), availability of histological tumor material (OR = 2.46; p < 0.001), and clinical stage of metastatic disease (p = 0.002). Other factors associated with guideline-adherent biomarker testing included diagnosis at academic center (OR = 1.87; p = 0.002) and patient's region of residence (p < 0∙001)., Conclusion: Optimization of the chain-of-care of predictive biomarker testing in patients with NSCLC in the Netherlands is needed to provide adequate care for these patients., Competing Interests: Declaration of Competing Interest WT has received consulting fees from Merck Sharp and Dohme, Bristol-Myers Squibb, and Altana (fees to institution), is board member of Dutch Society of Pathology and member of Council for Research and Innovation of the Federation of Medical Specialists (FMS). LvK has received institutional grants or contract from Amgen, AstraZeneca, Bayer, Janssen-Cilag, Merck, Roche, and Servier, has received institutional payments or honoraria from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer, and Roche, has received institutional support for attending meeting and/or travel from Roche, has participated on a Data Safety Monitoring Board or Advisory Board from Janssen-Cilag, Merck, and Roche, has a leadership or fiduciary role in the Commission Personalized Medicine – Belgium (unpaid), has stock or stock options in Cyclomics (institutional/personal). AvdW has received grants or contracts from AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche, and Takeda, has received consulting fees from AstraZeneca, Janssen, Lilly, Roche, and Takeda, has received payments or honoraria from AstraZeneca, BMS, Lilly, Pfizer, and Roche, has a leadership or fiduciary role in the oncology section NVALT, guideline committee NSCLC and CUP, dure geneesmiddelen committee NVALT and FMS. ES has received unrestricted grants (all paid to UMCG institution) from Abbott, Biocartis, AstraZeneca, Invitae/Archer, Bayer, Bio-Rad, Roche, Agena Bioscience, CC Diagnostics, MSD/MERCK, and Boehringer Ingelheim, has received consulting fees (all paid to UMCG institution) from MSD/Merck, AstraZeneca, Roche, Novartis, Bayer, BMS, Lilly, Amgen, Illumina, Agena Bioscience, CC Diagnostics, Janssen Cilag (Johnson & Johnson), Astellas Pharma, GSK, Sinnovisionlab, and Sysmex, has received payments or honoraria (all paid to UMCG institution) from Bio-Rad, Seracare, Roche, Biocartis, Lilly, Agena Bioscience, and Illumina, has received support for attending meetings and/or travel from BioRad, Biocartis, Ageno Sciences, and Illumina, is a board member for the Dutch Society of Pathology (unpaid), European Society of Pathology (unpaid), European Liquid Biopsy Society (unpaid), is a secretary/member of the advisory committee for assessment of molecular diagnostics (cieBOD) (honoraria paid to UMCG institution), is committee member of national guideline advisory (honoraria paid to UMCG institution). SW received unrestricted research grants and speaker’s fees from Bayer, Roche, Astra Zeneca, Pfizer, MSD, BMS, Novartis, Lilly, Amgen, Logex, all paid to the UMCG. He is chair of Palga foundation and vice chair of the scientific council from the Dutch Cancer Society (unpaid). All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The recent WHO classification of skin tumors has underscored the importance of acknowledging intermediate grade melanocytic proliferations. A multistep acquisition of oncogenic events drives the progressive transformation of nevi into melanomas. The various pathways described are modulated by the initial oncogenic drivers that define the common, blue, and Spitz nevi groups. Intermediate lesions are most often the result of a clonal evolution within such nevi. Based on this established classification, we have suggested for each pathway a practical diagnostic approach, benefiting from the recently developed molecular tools, both in the setting of general pathology labs and expert centers. Moreover, recommendations regarding the re-excision and clinical follow-up are given to support decision-making in multidisciplinary tumor boards., (© 2021. Crown.)

Diagnostic histopathology of soft tissue tumors can be troublesome as many entities are quite rare and have overlapping morphologic features. Many soft tissue tumors harbor tumor-defining gene translocations, which may provide an important ancillary tool for tumor diagnosis. The NanoString nCounter platform enables multiplex detection of pre-defined gene fusion transcripts in formalin-fixed and paraffin-embedded tissue. A cohort of 104 soft tissue tumors representing 20 different histological types was analyzed for the expression of 174 unique gene fusion transcripts. A tumor-defining gene fusion transcript was detected in 60 cases (58%). Sensitivity and specificity of the NanoString assay calculated against the result of an alternative molecular method were 85% and 100%, respectively. Highest diagnostic coverage was obtained for Ewing sarcoma, synovial sarcoma, myxoid liposarcoma, alveolar rhabdomyosarcoma, and desmoplastic small round cell tumor. For these tumor types, the NanoString assay is a rapid, cost-effective, sensitive, and specific ancillary screening tool for molecular diagnosis. For other sarcomas, additional molecular testing may be required when a translocation transcript is not identified with the current 174 gene fusion panel., (© 2020 The Authors. Genes, Chromosomes & Cancer published by Wiley Periodicals, Inc.)

Background: Despite the excellent prognosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to predict clinical outcome., Methods: We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The Kaplan-Meier method and Cox proportional hazard model were applied for survival and multivariable analyses. A machine-learning approach was used to validate variables for predicting recurrence and death., Results: Of 1021 included cancers, 17.7% were rated L1CAM-positive. Of these L1CAM-positive cancers, 51.4% recurred during follow-up compared with 2.9% L1CAM-negative cancers. Patients bearing L1CAM-positive cancers had poorer disease-free and overall survival (two-sided Log-rank P < .001). Multivariable analyses revealed an increase in the likelihood of recurrence (hazard ratio [HR] = 16.33; 95% confidence interval [CI] = 10.55 to 25.28) and death (HR = 15.01; 95% CI = 9.28 to 24.26). In the L1CAM-negative cancers FIGO stage I subdivision, grading and risk assessment were irrelevant for predicting disease-free and overall survival. The prognostic relevance of these parameters was related strictly to L1CAM positivity. A classification and regression decision tree (CRT)identified L1CAM as the best variable for predicting recurrence (sensitivity = 0.74; specificity = 0.91) and death (sensitivity = 0.77; specificity = 0.89)., Conclusions: To our knowledge, L1CAM has been shown to be the best-ever published prognostic factor in FIGO stage I, type I endometrial cancers and shows clear superiority over the standardly used multifactor risk score. L1CAM expression in type I cancers indicates the need for adjuvant treatment. This adhesion molecule might serve as a treatment target for the fully humanized anti-L1CAM antibody currently under development for clinical use.

Expression of activated leukocyte cell adhesion molecule (ALCAM)/CD166 correlates with the aggregation and metastatic capacity of human melanoma cell lines (Am J Pathol 1998, 152:805-813). Immunohistochemistry on a series of human melanocytic lesions reveals that ALCAM expression correlates with melanoma progression. Most nevi (34/38) and all thin melanomas studied (Clark levels I and II) did not express ALCAM. In contrast, immunoreactivity was detected in the invasive, vertical growth phase of 2 of the 13 Clark level III lesions tested. The fraction of positive lesions further increased in Clark level IV (13/19) and in Clark level V (4/4) lesions. ALCAM expression was exclusively detectable in the vertical growth phase of the primary tumor. In melanoma metastases, approximately half of the lesions tested (13/28) were ALCAM positive. According to the Breslow-thickness, ALCAM expression was observed in less than 10% of the lesions that were thinner than 1.5 mm and in over 70% of the lesions that were thicker than 1.5 mm. Our results strongly suggest that ALCAM plays an important role in melanocytic tumor progression and depict it as a new molecular marker for neoplastic progression of primary human melanoma.