Keratin 5 in Lung Cancer Specimens: Comparison of Four Antibody Clones and KRT5 mRNA-ISH.

Recent improvements in the medical treatment of non-small cell lung carcinoma have made the histopathological distinction between adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) increasingly important. One immunohistochemical marker of squamous differentiation is Keratin 5 (K5). Several K5 antibody clones are commercially available, and data from external quality assessment (NordiQC) have shown large variations in their performance. However, comparing antibody performance characteristics of optimized K5 immunohistochemical assays in lung cancer specimens is needed. Tissue microarrays comprising 31 SCCs, 59 ACs, 17 large cell carcinomas, 8 large cell neuroendocrine carcinomas, 5 carcinosarcomas, and 10 small cell carcinomas were included. Serial sections from the tissue microarrays were stained using optimized assays based on the K5 mouse monoclonal antibodies D5/16 B4 and XM26, and the K5 rabbit monoclonal antibodies SP27 and EP1601Y, respectively. The staining reactions were assessed using H-score (0-300). In addition, p40 immunohistochemistry and KRT5 mRNA-ISH analyses were conducted. Clone SP27 showed significantly higher analytical sensitivity than the other 3 clones. However, a distinct positive reaction was observed in 25% of the ACs using clone SP27 but not with the other clones. Clone D5/16 B4 displayed granular staining in 14 ACs, probably representing Mouse Ascites Golgi-reaction. A weak, scattered expression of KRT5 mRNA was seen in 71% of the ACs. In conclusion, the K5 antibody clones D5/16 B4, EP1601Y, and XM26 showed equal sensitivity in lung cancer specimens, but D5/16 B4 also showed nonspecific Mouse Ascites Golgi-reaction. Clone SP27 demonstrated superior analytical sensitivity but lower clinical specificity in the differential diagnosis of SCC versus AC.

Cardiovascular autonomic reflex tests using a handheld device in the diagnosis of cardiovascular autonomic neuropathy in patients with schizophrenia.

Study objective: This study investigated whether schizophrenia and the duration of schizophrenia were associated with cardiovascular autonomic neuropathy (CAN) by using heart rate variability (HRV) as a marker. Design: Cross-sectional study. Setting: The examinations were conducted at the Centre for Psychosis Research and at the Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. Participants: 240 patients with first-episode and chronic schizophrenia and 180 controls. Interventions: CAN was assessed by the cardiovascular reflex tests (CARTs): HR, RS ratio, E:I ratio, and VM using a handheld device. Main outcome measures: One abnormal CART was interpreted as borderline CAN and ≥2 abnormal CARTs established definitive CAN. Borderline CAN and definitive CAN together was categorized as overall CAN. Analyses were adjusted for age, sex, smoking, overweight, and hypercholesterolemia. Results: A total of 240 patients with schizophrenia (median age 42.5 [28.8, 52.3], 42.9 % women) and 180 controls (median age 45.8 [24.0, 60.1], 47.8 % women) were included, with 50.8 % of patients with schizophrenia having overall CAN compared to 27.2 % among controls. Dividing patients into patients with first-episode and chronic schizophrenia, 32.9 % vs 10 % (p < 0.001) and 59.1 % vs 41 % (p < 0.001) had overall CAN compared with controls, respectively. Schizophrenia was significantly associated with overall CAN (OR, 2.80; 95%CI, 1.75-4.50), with an OR of 2.31 (95%CI, 1.14-4.68) for first-episode schizophrenia and an OR of 2.97 (95%CI, 1.81-4.87) for chronic schizophrenia. Conclusion: It was demonstrated that a diagnosis of schizophrenia was associated with CAN. Patients with chronic schizophrenia had a significantly higher prevalence of CAN compared to patients with first-episode schizophrenia, suggesting an association between the duration of schizophrenia and CAN.