Significance of MYB and NTRK Expression in Head and Neck Adenoid Cystic Carcinoma.

BACKGROUND/AIM: Adenoid cystic carcinoma (ACC) is an aggressive neoplasm even though it has low-grade histological appearance and slow growth. The aim of this study was to identify the immunohistochemical and molecular characteristics of ACC, as well as their correlation with the clinical course of patients. PATIENTS AND METHODS: This is a retrospective multicenter analysis. We included 50 patients diagnosed with ACC in the head and neck between 2000 and 2021. The expression of MYB proto-oncogene transcription factor (MYB), neurotrophic tyrosine kinase receptor (NTRK), human epidermal receptor-2 (HER-2), and Ki-67 was examined through immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). We also performed a clinical follow-up of the patients. RESULTS: The median age of the patients was 58.5 years; moreover, 54% of the patients were male. Compared with female patients, male patients were at a higher risk of both recurrence and death. No HER-2-positive cases were revealed. MYB expression was positive in 28 (56%) cases. However, MYB expression did not significantly affect survival. NTRK expression was positive in eight (16%) cases. NTRK-positive patients had worse overall survival (OS) than NTRK-negative patients (p=0.0246). Additionally, the percentage of NTRK-stained cells was negatively correlated with disease-free survival (p=0.0016) and OS (p=0.0027). CONCLUSION: There was no correlation between MYB positivity and survival. Contrarily, NTRK-positive patients had worse survival, indicating that NTRK is a negative prognostic factor. Tropomyosin receptor kinase inhibitors can be used to treat these patients. Furthermore, MYB-targeted inhibitors are promising therapeutic agents.

Low expression of miR-20b-5p indicates favorable prognosis in laryngeal squamous cell carcinoma, especially in patients with non-infiltrated regional lymph nodes.

PURPOSE: Tumor recurrence and distant metastasis are very common in laryngeal squamous cell carcinoma (LSCC). In this study, we examined the potential prognostic value of microRNA-20b-5p (miR-20b-5p), a component of the tumor-related miR-106a/363 cluster. MATERIALS AND METHODS: Total RNA was purified from 105 tissue specimens resected from patients having undergone surgical treatment for primary LSCC. After in vitro polyadenylation and reverse transcription, a sensitive real-time quantitative polymerase chain reaction (qPCR) methodology was applied for the relative quantification of miR-20b-5p levels. Then, we proceeded with biostatistical analysis, seeking to assess the prognostic value of miR-20b-5p expression in LSCC. RESULTS: miR-20b-5p positivity constitutes a predictor of inferior DFS and OS in LSCC (P < 0.001 and P = 0.002, respectively). The significant prognostic value of miR-20b-5p expression status seems to be independent of tumor size, histological grade, and TNM stage, as revealed by the multivariate bootstrap Cox regression analysis. Kaplan-Meier survival analysis showed also that miR-20b-5p expression status can stratify LSCC patients with non-infiltrated regional lymph nodes (N0) into two subgroups with distinct prognosis (P = 0.004 and P = 0.004, respectively). CONCLUSIONS: The miR-20b-5p expression status is a promising molecular tissue biomarker in LSCC, with an independent prognostic value, and thus merits further validation in larger cohorts of patients.

Expression of vimentin (VIM) and metastasis-associated 1 (MTA1) protein in laryngeal squamous cell carcinoma are associated with prognostic outcome of patients.

PURPOSE: Laryngeal squamous cell carcinoma (LSCC), a common type of head and neck cancer, is associated with high rates of metastasis and recurrence. In this study, we investigated the potential combinatorial prognostic value of NOTCH1, Vimentin (VIM), and Metastasis-associated 1 (MTA1) protein in LSCC, using immunohistochemistry. MATERIALS AND METHODS: Tissue specimens from 69 patients with LSCC were immunohistochemically evaluated for the protein expression of NOTCH1, VIM, and MTA1. Then, biostatistical analysis was performed, in order to assess the prognostic value of the expression of each one of these proteins. RESULTS: NOTCH1 expression status was not a significant prognosticator in LSCC, as shown in Kaplan-Meier survival analysis. On the contrary, both VIM and MTA1 seem to have an important prognostic potential, independently of TNM staging and histological grade of the tumor. In fact, positive VIM expression was shown to predict patients' relapse and poor outcome regarding patients' overall survival, in contrast with MTA1, the positive expression of which predicts higher disease-free survival (DFS) and overall survival (OS) rates in LSCC. CONCLUSIONS: VIM and MTA1 constitute potential tumor biomarkers in LSCC and could be integrated into a multiparametric prognostic model. Undoubtedly, their prognostic value needs further validation in larger cohorts of LSCC patients.

Distinctive expression profiles of Caveolin-1 and Notch-1 protein in patients with nasal polyps or sinonasal inverted papillomas.

BACKGROUND: Nasal polyposis (NP) and sinonasal inverted papillomas (SIP) are considered benign lesions capable of recurrence or malignant transformation although not with the same prevalence. Since fluctuations of Caveolin-1 and Notch-1 proteins expression have been reported in many pathologies, the current study aimed to investigate their involvement in the epithelial transformation observed in SIPs compared to NP. METHODS: Immunohistochemical expression of Caveolin-1 and Notch-1 proteins was assessed in 104 patients with sinonasal lesions (45 NP, 45 SIP and 14 NP with SIP), semiquantively (percentage times intensity). Proteins expression profiles were evaluated statistically for their correlation with patients demographic and clinicopathological variables (grade of dysplasia, inflammation, recurrence) as well as with markers of proliferation (Ki67) and apoptosis (7-AAD) as determined by flow cytometry analysis. RESULTS: SIP lesions presented increased Caveolin-1 immunopositivity compared to NP (62.2%, vs 40.9%; p = 0.045). Cytoplasmic staining was observed only in epithelium's basal and suprabasal layers. Caveolin-1 positivity was not related to Ki67 expression, apoptosis, inflammation or dysplasia, eventhough 81.8% of highly immunopositive lesions were dysplastic (p = 0.03). Also, smokers presented significantly increased immunopositivy (p = 0.03). In contrast SIP lesions presented reduced Notch-1 expression compared to NP (68.9% vs 100%; p < 0.001). Dysplastic lesions presented low Notch-1 immunopositivity (p < 0.001). Enhancement of Notch-1 gene expression was also associated with inflammation. CONCLUSIONS: The herein presented data suggest that the expression profiles of Caveolin-1 and Notch-1 proteins in sinonasal pathologies are distinctive and that could be explored as potential targets for the development of alternative therapeutic approaches.

Dysphagia Caused by Chronic Laryngeal Edema.

A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office.

Evaluation of acute/late toxicity and local recurrence in T1-T2 glottic carcinoma treated with accelerated hypofractionated 3D-conformal external beam radiotherapy (3D-CRT).

BACKGROUND: The aim of the study was to evaluate the efficacy, as well as the acute and late toxicity of an accelerated hypofractionated 3DCRT schedule as radical treatment in patients with organ confined glottic cancer cT1-2N0. PATIENTS AND METHODS: Between June of 2004 and September 2010, 47 retrospectively selected patients (29 males, 18 females) diagnosed with organ confined T1 or T2 glottic cancer, were treated with external 3DCRT in an accelerated hypofractionation schedule. The median age was 70 years. A dose of 64.4 Gy in 28 daily fractions was prescribed. The primary study endpoints were to assess the acute and late effects of radiation toxicity, according to the EORTC/ RTOG scale, as well as the therapeutic impact of this schedule in terms of local recurrence. RESULTS: The median follow up was 36 months. At the end of radiotherapy, grade I, II and III acute toxicity was observed in 34, 9 and4 patients, respectively. Late grade I and II toxicity was observed in 25 and in 8 patients respectively. Only two local recurrences were observed, 15 and 24 months post 3DCRT respectively. CONCLUSIONS: Our radiotherapy schedule achieves a high locoregional control rate with the advantage of voice preservation. The proposed hypofractionated schedule can be recommended as a standard radiotherapy treatment, since these results are comparable with those of conventional fractionation schedules.

The role of the VEGF-C/-D/flt-4 autocrine loop in the pathogenesis of salivary neoplasms.

Salivary gland cells produce and secrete VEGF under normal conditions, but this property has not been studied in salivary gland neoplasms. The aim of this study was to evaluate the expression of VEGF-C/VEGF-D/flt-4 in salivary gland tumors. Thirty-one salivary gland tumors (19 with and 12 without myoepithelial differentiation) were examined. Immunostaining for VEGF-C/VEGF-D/flt-4, p63 and SMA was carried out. The chi-square distribution and the Pearson correlation were applied. A statistically significant relationship (p<0.05) was found in the group of tumors with myoepithelial differentiation regarding simultaneous positive staining for VEGF-C/VEGF-D and flt-4. All pleomorphic adenomas (PA) exhibited a statistically significant coexpression of the three antibodies. p63 and SMA were strongly expressed in the same areas as VEGF-C, VEGF-D and flt-4. The cells responsible for the strong expression of VEGF-C, VEGF-D and flt-4 in PAs are myoepithelial cells. Coexpression of flt-4 and its ligands in all PAs suggests the presence of a dominant VEGF-C/VEGF-D/flt-4 axis in this tumor.

Simultaneous over activation of EGFR, telomerase (h TERT), and cyclin D1 correlates with advanced disease in larynx squamous cell carcinoma: a tissue microarray analysis.

Overexpression of Epidermal Growth Factor Receptor (EGFR) and also of cell cycle control proteins, such as cyclin D1 is a frequent event in squamous cell carcinoma of the larynx (LSSC). Our aim was to correlate their protein levels with telomerase catalytic subunit (h-TERT) expression. Using tissue microarray technology, fifty-five paraffin embedded histologically confirmed primary LSSCs and also ten dysplastic lesions were cored at a diameter of 1.5 mm. Immunohistochemistry (IHC) was performed by the use of anti-EGFR, anti-cyclin D1, and anti-h TERT monoclonal antibodies. Chromogenic in situ hybridization (CISH) analysis was also applied using EGFR gene and chromosome 7 probes, respectively. EGFR, cyclin D1 and h-TERT protein overexpression was observed in 48/55 (87.2%), 19/55 (34.5%) and 21/55 (38.1%) carcinoma cases, respectively. EGFR protein expression was statistically associated with grade (P=0.01), and also with stage (P=0.001) of the examined tumors. Borderline statistical significance was assessed correlating overall cyclin D1 expression to h TERT expression (P=0.06). Simultaneous up regulation of the three proteins was established in 7/55 (12.7%) cases, correlated to the stage of the tumors (P=0.05). EGFR gene amplification was observed in 7/65 (10.7%) carcinomas and dysplasias, whereas chromosome 7 aneuploidy was detected in 4/65 (6.1%) of those cases.Simultaneous up regulation of EGFR, cyclin D1 and h TERT proteins correlates with advanced stage in LSCC. EGFR gene amplification and not only protein over expression maybe is the eligible criterion for targeted therapeutic strategies in those patients.

Myofascial pain syndromes in the maxillofacial area: a common but underdiagnosed cause of head and neck pain.

Myofascial pain syndromes (MPS) are a large group of muscular disorders, characterized by the presence of hypersensitive spots called trigger points (TP). The maxillofacial region is a high-frequency area for developing TPs. The aim of this paper was to review and summarize the most important methods of management. A literature review was carried out from Medline and database sources. A range of study types were selected for analysis. TP formation and activity result in a reverberating circuit of sustained neural activity. Central mechanisms, primarily associated with psychosocial factors, lead to chronicity. Other synergistic factors are metabolic disorders, nutritional imbalances and regional anatomic disorders. A detailed history and physical examination are important for proper diagnosis. The aim of MPS management is pain relief and restoration of full muscle function. Treatment may require enhancing central inhibition, using pharmacological and/or behavioural techniques, and reducing peripheral inputs, using physical therapy. There are various effective methods of inactivation of TPs. Recognition and reduction of synergistic factors may be important. MPS have a very high prevalence in the general population, despite low awareness among physicians, affecting patients' quality of life. There is a need for interdisciplinary teams of health professionals to achieve proper diagnosis, management and sustainable outcomes.

Neurotoxicity of BFM-95 on the medial olivocochlear bundle assessed by means of contralateral suppression of 2f1-f2 distortion product otoacoustic emissions.

OBJECTIVE: Berlin-Frankfurt-Munster 95 (BFM-95) is a common chemotherapeutic protocol against acute lymphoblastic leukemia (ALL). This prospective study investigates whether this protocol has an adverse effect on the medial olivocochlear bundle (MOCB) and/or outer hair cells' (OHCs) function. The distortion product otoacoustic emissions (DPOAEs) and their suppression by means of contralateral application of white noise were used for assessing the function of OHCs and the MOCB, respectively. STUDY DESIGN: Prospective study. SETTING: Oncology and otorhinolaryngology departments in a pediatric hospital. PATIENTS: Thirty-six children treated with ALL-BFM-95. INTERVENTIONS: Before chemotherapy, a baseline audiologic evaluation with tympanogram, standard and extended high frequency, pure-tone audiometry, and DPOAEs in the absence and presence of white noise was performed in all children. This population was divided in three groups. In a first group (n = 12), the evaluation was repeated after four sessions of vincristine administration; in the second group (n = 12), after 8 sessions; and in the third group (n = 12), several months after completion of the protocol. MAIN OUTCOME MEASURE: DPOAEs suppression by contralateral application of white noise. RESULTS: In the first and the third groups, we observed no changes in DPOAE amplitudes. Nevertheless, in the second group, the DPOAEs demonstrated significant decrease at 1416, 1685, 2002, and 2380 Hz. At baseline examination, all groups presented significant suppression at all frequencies. After eight vincristine sessions, instead of suppression, an increase of amplitudes was noted at 5 of 12 frequencies. Efferent-mediated DPOAE suppression reappeared in the third group at all frequencies (significant at 5 of 12 frequencies). CONCLUSION: ALL-BFM-95 seems to exert an early and reversible toxic effect on the MOCB, whereas its effects on OHCs are minimal and reversible. These minimal cochleotoxic and neurotoxic properties of ALL-BFM-95 might prove useful for research studies on the role of efferent innervation in hearing.