Tissue factor expression in salivary gland carcinoma: a potential novel therapeutic target for advanced disease.

Background: Salivary gland carcinomas (SGC) are rare head and neck malignancies with diverse molecular profiles and treatment challenges. Tissue factor (TF), a transmembrane glycoprotein involved in cancer pathophysiology, has emerged as a potential therapeutic target.

Objectives: The objective of this study was to investigate TF expression in SGC and its correlation with clinicopathological data.

Histological and genetic criteria define a clinically relevant subgroup of HPV-positive oropharyngeal carcinoma.

Introduction: Subgroups with a poorer prognosis exist among patients with human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC). This study aims to identify histological and genetic differences within HPV-positive OPSCC and correlate these findings with patient outcomes.

Methods: The study included 102 OPSCC patients, all tested positive for high-risk HPV DNA and p16INK4a expression.

The Impact of Lesion-Specific and Sampling-Related Factors on Success of Salivary Gland Fine-Needle Aspiration Cytology.

Purpose: Ultrasound-guided fine-needle aspiration cytology (FNAC) is a widely used diagnostic procedure which facilitates the differentiation of salivary gland lesions. Although the performance of salivary gland FNAC (SG-FNAC) has improved since the introduction of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), the range of the reported performance is still wide. Therefore, the aim of this study was to determine lesion- and sampling-related factors that influence the success of SG-FNAC.

Benchmark of screening markers for KEAP1/NFE2L2 mutations and joint analysis with the K1N2-score.

Our recently published K1N2-score robustly predicts KEAP1/NFE2L2-mutations and pathway activation status, while its accessibility might be limited. We tested if the RNA expression data of six pathway-related genes and NQO1-IHC might be a reliable alternative using 348 KEAP1/NFE2L2 mutation-enriched NSCLC. While TXNRD1 RNA testing was the best-performing single-gene test, the combination of single-gene screening and validation with the K1N2-score achieved the highest performance when predicting mutation status or pathway activation.

[Clinical and molecular epidemiology of malignant salivary gland tumors].

Salivary gland carcinomas are a rare and heterogeneous group of malignant tumors, accounting for 3-6% of all malignant tumors in the head and neck region. The 1-, 3- and 5-year survival rates are 83%, 69% and 63% respectively. Due to new molecular pathological and genetic findings, new entities are constantly being defined as part of the recurring WHO classification of salivary gland carcinomas, so that the incidence rates of the entities are subject to constant change.

The extent of androgen receptor and HER2 expression allows for targeted therapy in most cases of salivary duct carcinoma: analysis of clinical and histopathological data in a tertiary care center.

Purpose: The incidence of salivary duct carcinoma (SDC) seems to be underestimated due to inaccurate classification. Further, the frequency of SDC patients with targeted therapy options according to current guidelines is unclear. Therefore, this study aimed at (a) describing the proportion of SDC among salivary gland carcinoma (SGC) before and after reclassification of cases initially classified as adenocarcinoma, not otherwise specified (ANOS); and (b) quantifying the frequency of SDC patients with targeted therapy options.

Nectin-4 is frequently expressed in primary salivary gland cancer and corresponding lymph node metastases and represents an important treatment-related biomarker.

Many locally advanced and metastatic salivary gland carcinomas (SGC) lack therapeutic targets. Enfortumab vedotin, an antibody-drug conjugate binding to Nectin-4, recently gained FDA approval for third-line urothelial carcinoma. Therefore, the aim of this study was to assess the expression of Nectin-4 in primary SGC and corresponding lymph node metastases and to correlate it with clinicopathological data.

KEAP1/NFE2L2 Pathway Signature Outperforms KEAP1/NFE2L2 Mutation Status and Reveals Alternative Pathway-Activating Mutations in NSCLC.

Introduction: Activation of the antioxidant KEAP1/NFE2L2 (NRF2) pathway leads to increased glutamine dependence and an aggressive phenotype in NSCLC. Because this pathway has been explored as a clinical target, we developed a transcriptomic signature for identifying KEAP1/NFE2L2-activated tumors.

Methods: A total of 971 NSCLC samples were used to train an expression signature (K1N2-score) to predict KEAP1/NFE2L2 mutations.

The extracellular matrix landscape in salivary gland carcinomas is defined by cellular differentiation via expression of three distinct protein modules.

The extracellular matrix (ECM) is an integral part of the tumor microenvironment of carcinomas. Even though salivary gland carcinomas (SGCs) display a range of tumor cell differentiation and distinct extracellular matrices, their ECM landscape has not been characterized in depth. The ECM composition of 89 SGC primaries, 14 metastases, and 25 normal salivary gland tissues was assessed using deep proteomic profiling.

Multi-Class Cancer Subtyping in Salivary Gland Carcinomas with MALDI Imaging and Deep Learning.

Salivary gland carcinomas (SGC) are a heterogeneous group of tumors. The prognosis varies strongly according to its type, and even the distinction between benign and malign tumor is challenging. Adenoid cystic carcinoma (AdCy) is one subgroup of SGCs that is prone to late metastasis.

CD138 Is Expressed in Different Entities of Salivary Gland Cancer and Their Lymph Node Metastases and Therefore Represents a Potential Therapeutic Target.

Advanced salivary gland carcinomas (SGC) often lack therapeutic options. Agents targeting CD138 have recently shown promising results in clinical trials for multiple myeloma and a preclinical trial for triple-negative breast cancer. Immunohistochemistry for CD138 was performed for all patients who had undergone primary surgery for SGC with curative intent.

[Diagnostics and treatment of secondary malignancies of the parotid gland-An overview].

Background: Secondary malignancies of the parotid gland frequently have a cutaneous origin and the incidence in central Europe is increasing.

Objective: The aim of this review article was to present the epidemiology, (differential) diagnostics and treatment of secondary malignancies of the parotid gland.

Material And Methods: A literature search of the current guidelines and evidence was carried out in the web-based databank PubMed.

Patterns of Tumor Infiltrating Lymphocytes in Adenoid Cystic Carcinoma of the Head and Neck.

Adenoid cystic carcinoma (ACC) is a rare malignancy in the head and neck. The prognosis remains poor and late recurrences often occur after 5 years and later. To date, there are no reliable prognostic markers for ACC.

[Novel therapeutic approaches for salivary gland carcinomas].

Novel therapeutic options for the treatment of salivary gland malignancies have emerged due to the improvement and distribution of molecular pathological testing methods and the availability of targeted therapies. Since they are less toxic, these new agents are a valuable alternative to conventional cytotoxic chemotherapy. On the one hand, there are new entity-specific therapies such as NTRK inhibitor therapy for secretory carcinomas and axitinib therapy for adenoid cystic carcinomas.

Misleading Morphologic and Phenotypic Features (Transdifferentiation) in Solitary Fibrous Tumor of the Head and Neck: Report of 3 Cases and Review of the Literature.

Solitary fibrous tumor (SFT) is a rare fibroblastic neoplasm with potentially malignant behavior that may develop in any anatomic site and may involve the head and neck (H&N) region as well. Although typical SFT has a relatively characteristic morphology, its morphologic spectrum is extraordinarily broad and also includes rare cases with dedifferentiation or transdifferentiation which result in aberrant morphologic and/or immunohistochemical features. However, since virtually all cases are molecularly characterized by NAB2::STAT6 gene fusions, molecular genetic methods or STAT6 immunohistochemistry can be effectively used in confirming the diagnosis.

Comprehensive Analysis of VEGFR2 Expression in HPV-Positive and -Negative OPSCC Reveals Differing VEGFR2 Expression Patterns.

VEGF signaling regulated by the vascular endothelial growth factor receptor 2 (VEGFR2) plays a decisive role in tumor angiogenesis, initiation and progression in several tumors including HNSCC. However, the impact of HPV-status on the expression of VEGFR2 in OPSCC has not yet been investigated, although HPV oncoproteins E6 and E7 induce VEGF-expression. In a series of 56 OPSCC with known HPV-status, VEGFR2 expression patterns were analyzed both in blood vessels from tumor-free and tumor-containing regions and within tumor cells by immunohistochemistry using densitometry.

Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a deadly disease with limited options for targeted therapy. With the help of next-generation sequencing studies over the last decade, we gained an understanding of the genomic architecture of EAC. The tumor suppressor gene is mutated in 70 to 80% of tumors followed by genomic alterations in , , , , and a long tail of less frequently mutated genes.

Mutually Exclusive Expression of COL11A1 by CAFs and Tumour Cells in a Large panCancer and a Salivary Gland Carcinoma Cohort.

Procollagen 11A1 (COL11A1) is a central component of the extracellular matrix in many carcinomas, which is considered to be mainly produced by cancer associated fibroblasts (CAFs). As COL11A1 expression correlates with adverse prognosis and is implicated in chemoresistance, it is a promising putative target. For the first time, we used RNA in-situ hybridization to systematically identify the cells that produce COL11A1 in the ten most prevalent carcinoma types, lymphomas (n = 275) and corresponding normal tissue (n = 55; panCancer cohort).

Trophoblast Cell Surface Antigen 2 (Trop-2) Protein is Highly Expressed in Salivary Gland Carcinomas and Represents a Potential Therapeutic Target.

Treatment options for unresectable, recurrent or metastatic salivary gland carcinomas (SGC) are scarce. Trophoblast cell surface antigen 2 (Trop-2) is a transmembrane glycoprotein that is involved in a variety of oncogenic cell signaling pathways. Its potential as a target for the antibody-drug conjugate sacituzumab govitecan has already been demonstrated in different tumor entities.

Survival after parotid gland metastases of cutaneous squamous cell carcinoma of the head and neck.

Purpose: Malignant tumours in the parotid gland can originate either from the gland itself or as a result of metastatic spread of other tumours, such as cutaneous squamous cell carcinomas (CSCC) of the head and neck area. The aim of this study was to analyse and compare the clinical behaviour of primary as well as CSCC metastatic parotid cancers with special emphasis on therapy and oncologic outcome.

Methods: Clinical and histopathological data of 342 patients with parotid gland malignomas surgically treated in a tertiary referral centre between 1987 and 2015 were retrospectively assessed.

Expression profiling on subclasses of primary parotid gland carcinomas.

Introduction: The underlying molecular mechanisms of parotid gland carcinomas (PGC) are still unknown. Knowledge about the tumor-driving signaling pathways is necessary either for diagnostics or developing new therapeutic options in this heterogeneous and rare entity.

Material And Methods: 94 matching RNA formalin-fixed and paraffin-embedded tissue samples from PGC and the corresponding non-tumor area, RNA quality and quantity were sufficient for gene expression profiling of 770 genes using the NanoString's nCounter technology.

Expression Profiling of Extracellular Matrix Genes Reveals Global and Entity-Specific Characteristics in Adenoid Cystic, Mucoepidermoid and Salivary Duct Carcinomas.

The composition of the extracellular matrix (ECM) plays a pivotal role in tumour initiation, metastasis and therapy resistance. Until now, the ECM composition of salivary gland carcinomas (SGC) has not been studied. We quantitatively analysed the mRNA of 28 ECM-related genes of 34 adenoid cystic (AdCy; = 11), mucoepidermoid (MuEp; = 14) and salivary duct carcinomas (SaDu; = 9).