Maximilian Linxweiler

Background Head and neck squamous cell carcinomas (HNSCC) are frequently diagnosed in advanced stages, which limits therapeutic options and results in persistently poor patient outcomes. The aim of this study was to use liquid‐based swab cytology (LBC) in combination with dual immunocytochemical detection of migration and proliferation markers Sec62 and Ki67 in order to allow non‐invasive early detection of HNSCC as well as to analyse the diagnostic validity of this method for predicting the malignancy of suspicious oral lesions. Methods 104 HNSCC patients and 28 control patients, including healthy patients ( n = 17), papilloma ( n = 1) and leukoplakia patients ( n = 10), were included in this study. For all patients, an LBC swab followed by simultaneous immunocytochemical detection of Sec62 and Ki67 was performed. Immunocytochemical as well as cytopathological results were correlated with histological diagnoses and clinical findings. Results All HNSCC patients (100%) showed dual Sec62/Ki67 positivity, and all control patients except for the papilloma patient were negative for Sec62/Ki67 (96.4%), resulting in a 100% sensitivity and 96.4% specificity of Sec62/Ki67 dual stain for non‐invasive detection of HNSCC. The positive predictive value was 99% and the negative predictive value was 100%. Sec62 expression levels showed a positive correlation with tumour de‐differentiation ( p = 0.0489). Conclusion Simultaneous immunocytochemical detection of Sec62/Ki67 using LBC represents a promising non‐invasive and easy‐to‐apply tool for the early detection of HNSCC in routine clinical practice. This novel technique can help to avoid incisional biopsies and reduce the frequency with which general anaesthesia is used in diagnostic procedures in patients with suspicious oral lesions.

In the absence of targeted treatment options, neoadjuvant chemotherapy (NACT) is applied widely for triple-negative breast cancer (TNBC). Response to NACT is an important parameter predictive of oncological outcomes (progression-free and overall survival). An approach to the evaluation of predictive markers enabling therapy individualization is the identification of tumor driver genetic mutations. This study was conducted to investigate the role of SEC62, harbored at 3q26 and identified as a driver of breast cancer pathogenesis, in TNBC. We analyzed SEC62 expression in The Cancer Genome Atlas database, and immunohistologically investigated SEC62 expression in pre- and post-NACT tissue samples from 64 patients with TNBC treated at the Department of Gynecology and Obstetrics/Saarland University Hospital/Homburg between January 2010 and December 2018 and compared the effect of SEC62 on tumor cell migration and proliferation in functional assays. SEC62 expression dynamics correlated positively with the response to NACT (p ≤ 0.01) and oncological outcomes (p ≤ 0.01). SEC62 expression stimulated tumor cell migration (p ≤ 0.01). The study findings indicate that SEC62 is overexpressed in TNBC and serves as a predictive marker for the response to NACT, a prognostic marker for oncological outcomes, and a migration-stimulating oncogene in TNBC.