Background: HNSCC is the sixth most common cancer in humans and has still a very poor prognosis. The treatment methods so far are very often associated with mutilation and impairment in the quality of life. Except for p16 expression, there are no reliable prognostic markers in HNSCC so far. Ecotropic Viral Integration Site 1 (EVI1) is a well-described prognostic marker in leukemia and different types of solid cancers. In these, a high EVI1 expression is associated with a poor prognosis. In HNSCC, it is not known so far if EVI1 has any prognostic relevance. Materials and Methods: We used our representative tissue cohort of 389 primary HNSCCs, of which 57.2% had one or more lymph node metastases. Here EVI1 expression was analyzed via immunohistochemistry and correlated with the clinical characteristics of these patients. Results: Although in HNSCC EVI1 expression does not predict poor survival, a high EVI1 expression in the primary tumor correlates with a lymph node metastatic disease. Conclusion: Consequently, EVI1 may serve as a biomarker to predict an occult lymph node metastasis in a clinical nodal negative (cN0) HNSCC.

Head and neck squamous cell carcinoma (HNSCC)is the 6th most common cancer in humans worldwide and is associated with a poor prognosis for patients. NR2F6 has been identified as an immune checkpoint molecule in tumor-infiltrating T lymphocytes and is associated with a poor prognostic outcome in various cancers. The prognostic value of NR2F6 in HNSCC has not been described yet. We used a large, representative and clinically well-characterized cohort of 383 HNSCC patients, of which 22.4% developed a local recurrence. The NR2F6 expression was analyzed by using immunohistochemistry and was afterward correlated with clinical characteristics and clinicopathological features of HNSCC patients. Primary tumors from patients who develop a local recurrence have a higher NR2F6 expression than primary tumors which do not develop a local recurrence. Furthermore, a high NR2F6 expression is associated with poorer recurrence-free survival, although there is no correlation with overall survival. NR2F6 expression is independent of the T stage and UICC stage. NR2F6 might be a new prognostic biomarker for the early detection of local recurrences in HNSCC patients. Therefore, it may help to improve the recognition of patients who would benefit from more frequent follow-up examinations.

OBJECTIVE: It has been shown that optical coherence tomography (OCT) can identify brain tumor tissue and potentially be used for intraoperative margin diagnostics. However, there is limited evidence on its use in human in vivo settings, particularly in terms of its applicability and accuracy of residual brain tumor detection (RTD). For this reason, a microscope-integrated OCT system was examined to determine in vivo feasibility of RTD after resection with automated scan analysis. METHODS: Healthy and diseased brain was 3D scanned at the resection edge in 18 brain tumor patients and investigated for its informative value in regard to intraoperative tissue classification. Biopsies were taken at these locations and labeled by a neuropathologist for further analysis as ground truth. Optical OCT properties were obtained, compared, and used for separation with machine learning. In addition, two artificial intelligence–assisted methods were utilized for scan classification, and all approaches were examined for RTD accuracy and compared to standard techniques. RESULTS: In vivo OCT tissue scanning was feasible and easily integrable into the surgical workflow. Measured backscattered light signal intensity, signal attenuation, and signal homogeneity were significantly distinctive in the comparison of scanned white matter to increasing levels of scanned tumor infiltration (p < 0.001) and achieved high values of accuracy (85%) for the detection of diseased brain in the tumor margin with support vector machine separation. A neuronal network approach achieved 82% accuracy and an autoencoder approach 85% accuracy in the detection of diseased brain in the tumor margin. Differentiating cortical gray matter from tumor tissue was not technically feasible in vivo. CONCLUSIONS: In vivo OCT scanning of the human brain has been shown to contain significant value for intraoperative RTD, supporting what has previously been discussed for ex vivo OCT brain tumor scanning, with the perspective of complementing current intraoperative methods for this purpose, especially when deciding to withdraw from further resection toward the end of the surgery.

Background: Head and neck squamous cell carcinomas (HNSCCs) are among the most common cancers in humans worldwide and have a rather poor prognosis. TRIM24 has various intracellular functions and was identified in other cancer entities as a poor prognostic factor for patients. Methods: The expression of TRIM24 was evaluated by using immunohistochemistry. We used a large and representative cohort of 341 HNSCC patients. Data derived from immunohistochemistry evaluation was correlated with clinicopathological data from HNSCC patients. Results: The TRIM24 expression in HNSCC primary tumors is negatively correlated with the p16 status of the tumor tissues. Primary tumors of patients who developed a local recurrence were significantly more often positive for TRIM24. Kaplan–Meier analyses and Cox regression showed that patients with TRIM24 expressing tumors have significantly worse overall survival and progression-free survival and that TRIM24 expression is independent of other established risk factors. Conclusions: TRIM24 might be a new prognostic biomarker for the survival prognosis and early detection of local recurrences in HNSCC patients. It could be used for risk stratification of HNSCC patients and to identify those patients who are more prone to develop a local recurrence and therefore could profit from more frequent follow-up examinations.

HNSCC is the sixth most common cancer worldwide and the prognosis is still poor. Here, we investigated the prognostic implications of CDK7 and pMED1. Both proteins affect transcription, and their expression is altered throughout different tumor entities. pMED1 is phosphorylated by CDK7. Importantly, CDK7 and MED1 have been ascribed prognostic implications by various studies. However, their prognostic value in head and neck squamous-cell cancer (HNSCC) remains elusive. We applied immunohistochemical staining of CDK7 and pMED1 on our large and clinically well-characterized HNSCC tissue cohort comprising 419 patients. Software-aided quantification of staining intensity was performed as a measure of protein expression. The following results were linked to the clinicopathological features of our cohort and correlated in different tissue types (primary tumor, lymph node metastasis, distant metastasis, recurrence). Upregulation CDK7 was associated with worse 5-year overall survival as well as disease-free survival in HNSCC while being independent of other known prognostic factors such as p16-status. Also, CDK7 expression was significantly elevated in immune cell infiltrated tumors. In HNSCC CDK7 might serve as a novel prognostic marker to indicate the prognosis of patients. Furthermore, in vitro studies proved the feasibility of CDK7 inhibition with attenuating effects on cell proliferation underlining its remarkable translational potential for future therapeutic regimes.

Background: The intraoperative differentiation between tumour tissue, healthy brain tissue, and any sensitive structure of the central nervous system is carried out in modern neurosurgery using various multimodal technologies such as neuronavigation, fluorescent dyes, intraoperative ultrasound or the use of intraoperative MRI, but also the haptic experience of the neurosurgeon. Supporting the surgeon by developing instruments with integrated haptics could provide a further objective dimension in the intraoperative recognition of healthy and diseased tissue. Methods: In this study, we describe intraoperative mechanical indentation measurements of human brain tissue samples of different tumours taken during neurosurgical operation and measured directly in the operating theatre, in a time frame of maximum five minutes. We present an overview of the Young’s modulus for the different brain tumour entities and potentially differentiation between them. Results: We examined 238 samples of 75 tumour removals. Neither a clear distinction of tumour tissue against healthy brain tissue, nor differentiation of different tumour entities was possible on solely the Young’s modulus. Correlation between the stiffness grading of the surgeon and our measurements could be found. Conclusion: The mechanical behaviour of brain tumours given by the measured Young’s modulus corresponds well to the stiffness assessment of the neurosurgeon and can be a great tool for further information on mechanical characteristics of brain tumour tissue. Nevertheless, our findings imply that the information gained through indentation is limited.