EGFR and ERBB2 exon 20 insertion/duplication in advanced non–small cell lung cancer: genomic profiling and clinicopathologic features

BackgroundExon 20 (ex20) in-frame insertions or duplications (ins/dup) in epidermal growth factor receptor (EGFR) and its analog erb-b2 receptor tyrosine kinase 2 (ERBB2) are each detected in 1.5% of non–small cell lung cancer (NSCLC). Unlike EGFR p.L858R or ex19 deletions, ex20 ins/dup is associated with de novo resistance to classic EGFR inhibitors, lack of response to immune checkpoint inhibitors, and poor prognosis. US Food and Drug Administration has approved mobocertinib and amivantamab for targeting tumors with this aberration, but the number of comprehensive studies on ex20 ins/dup NSCLC is limited. We identified 18 cases of NSCLCs with EGFR/ERBB2 ex20 ins/dup and correlated the findings with clinical and morphologic information including programed death-ligand 1 (PD-L1) expression.MethodsA total of 536 NSCLC cases tested at our institution between 2014 and 2023 were reviewed. A custom-designed 214-gene next-generation sequencing panel was used for detecting DNA variants, and the FusionPlex CTL panel (ArcherDx) was used for the detection of fusion transcripts from formalin-fixed, paraffin-embedded tissue. Immunohistochemistry (IHC)for PD-L1 was performed using 22C3 or E1L3N clones.ResultsNine EGFR and nine ERBB2 ex20 ins/dup variants were identified from an equal number of men and women, 14 were non- or light smokers, and 15 had stage IV disease. All 18 cases were adenocarcinomas. Seven of the 11 cases with available primary tumors had acinar predominant pattern, two had lepidic predominant pattern, and the remainder had papillary (one case) and mucinous (one case) patterns. Ex20 ins/dup variants were heterogenous in-frame one to four amino acids spanning A767–V774 in EGFR and Y772–P780 in ERBB2 and were clustered in the loop following the C-helix and α C-helix. Twelve cases (67%) had co-existing TP53 variants. Copy number variation in CDK4 amplification was identified in one case. No fusion or microsatellite instability was identified in any case. PD-L1 was positive in two cases, low positive in four cases, and negative in 11 cases.ConclusionsNSCLCs harboring EGFR/ERBB2 ex20 ins/dup are rare and tend to be acinar predominant, negative for PD-L1, more frequent in non- or light smokers, and mutually exclusive with other driver mutations in NSCLC. The correlation of different EGFR/ERBB2 ex20 ins/dup variants and co-existing mutations with response to targeted therapy and the possibility of developing resistant mutations after mobocertinib treatment warrants further investigation

Prevalence of Toxoplasma gondii antibodies and intestinal parasites in stray cats from Nigde, Turkey

WOS: 000254814500011The prevalence of antibodies to Toxoplasma gondii was investigated by the Sabin-Feldman Dye test (SFDT) in 72 stray cats from Nigde, Turkey. A total of 55 (76.4%) of the analysed sera had antibodies to T. gondii. The seropositivity of T. gondii was 77.1% in male and 75.7% in female cats (P>0.05). Faeces of these cats were also examined by zinc sulphate flotation method for the presence of parasite oocysts and eggs of other parasites. Two protozoan parasites were identified as Isospora spp. (12.5%) and Eimeria spp. (4.1%) in cats. Toxoplasma gondii oocysts were not found in any faecal samples analysed. Two parasitic helminth species were observed: Toxocara cati (15.2%) and Toxascaris leonina (20.8%). These common ascarids were recorded for the first time in cats from Nigde

The epidemiology of adult fractures according to the AO/OTA fracture classification

BACKGROUND: The epidemiology of adult fractures has been changing timely, in a multifactorial fashion. The aim of this study was to put forward a recent 5-year epidemiological analysis of adult fractures, according to the current AO/OTA fracture classification, in the current decade of action for road safety. METHODS: 5324 adult patients who were diagnosed with at least one fracture related with orthopedics and traumatology in a level-one trauma center were included in this retrospective, epidemiological descriptive study. The patients were grouped according to their ages as; 18-35, 36-55, 56-69, and >= 70. The fractures were examined according to the AO/OTA classification. RESULTS: 5865 fractures were present in 5324 patients. The mean age of the patients was 48.6 +/- 21.5. The number of patients according to the age groups was as follows; 1947 (36.6%), 1636 (30.7%), 881 (16.5%), and 860 (16.2%), respectively. The most frequent three fractures according to the AO/OTA fracture classification were; 7 (hand 19.6%), 23 (distal forearm, 12.1%), and 8 (foot, 11.8%). About 54.4% and 45.4% of the patients were treated non-surgically and surgically, respectively. About 0.2% of the patients preferred an alternative treatment. Overall mortality rate was 0.4%. CONCLUSION: To the best of our knowledge, this study represents the first analysis of adult fractures according to the AO/OTA classification, over a 5-year period. As a future prospect, further multi-centric epidemiological studies are warranted to constitute a sustainable action plan for the prevention of major traumas

Anatomic pathology quality assurance: Developing an LIS based tracking and documentation module for intradepartmental consultations

Background: An electronic intradepartmental consultation system for anatomic pathology (AP) was conceived and developed in the laboratory information system (LIS) in 2019. Previously, all surgical pathology intradepartmental consultative activities were initiated and documented with paper forms which circulated with the pertinent microscopic slides and were eventually filed. In this study, we discuss the implementation and utilization of an electronic intradepartmental AP consultation system. Methods: Workflows and procedures were developed to organize intradepartmental surgical pathology consultations from the beginning to the end point of the consultative activities entirely using a paperless system that resided in the LIS. Results: The electronic consult system allowed electronic documentation of all steps of intradepartmental consultative activities. The system provided tracking ability for consulted cases and improved access to consult discussion for all departmental personnel, staff, and trainees. Consultation work queue was created for each pathologist and a summary of individual consultative workload was possible. Documentation of anatomic pathology quality assurance for intradepartmental consultative activity was easily assessed. Conclusions: The electronic intradepartmental consult system has allowed our department to electronically track intradepartmental consult cases, store the consultative opinion text with the case, record the pathologists involved, and document the consultation for internal quality assurance review as well as for accrediting organizations. Summarization of pathologist workload related to consultative activity was quantifiable and optimization of the consultative process was maximized for education in an academic setting

Automated labelling of cancer textures in colorectal histopathology slides using quasi-supervised learning

OBJECTIVE: To evaluate the performance of a quasisupervised statistical learning algorithm, operating on datasets having normal and neoplastic tissues, to identify larynx squamous cell carcinomas. Furthermore, cancer texture separability measures against normal tissues are to be developed and compared either for colorectal or larynx tissues

A Multicenter Study of Genotype Variation/Demographic Patterns in 2475 Individuals Including 1444 Cases With Breast Cancer in Turkey

Objective: Breast cancer (BC) is the most common cancer type in women and may be inherited, mostly in an autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and analysis of two genes, BRCA1 and BRCA2, which are strongly associated with BC, are included in these criteria. The aim of this study was to compare BC index cases with non-BC individuals in terms of genotype and diagnostic features to investigate the genotype/demographic information association. Materials and Methods: Mutational analyses for the BRCA1/BRCA2 genes was performed in 2475 individuals between 2013-2022 from collaborative centers across Turkey, of whom 1444 with BC were designated as index cases. Results: Overall, mutations were identified in 17% (421/2475), while the percentage of mutation carriers in cases of BC was similar, 16.6% (239/1444). BRCA1/BRCA2 gene mutations were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic cases. Mutations in BRCA1 were found in 4.9%, whereas 12% were in BRCA2 (p<0.05). Meta-analyses were performed to compare these results with other studies of Mediterranean-region populations. Conclusion: Patients with BRCA2 mutations were significantly more common than those with BRCA1 mutations. In sporadic cases, there was a lower proportion with BRCA1/BRCA2 variants, as expected, and these results were consistent with the data of Mediterranean-region populations. However, the present study, because of the large sample size, revealed more robust findings than previous studies. These findings may be helpful in facilitating the clinical management of BC for both familial and non-familial cases