Lectin-like Transcript-1 (LLT1) Expression in Oral Squamous Cell Carcinomas: Prognostic Significance and Relationship with the Tumor Immune Microenvironment.

Lectin-like transcript-1 (LLT1) expression is detected in different cancer types and is involved in immune evasion. The present study investigates the clinical relevance of tumoral and stromal LLT1 expression in oral squamous cell carcinoma (OSCC), and relationships with the immune infiltrate into the tumor immune microenvironment (TIME). Immunohistochemical analysis of LLT1 expression was performed in 124 OSCC specimens, together with PD-L1 expression and the infiltration of CD20+, CD4+, and CD8+ lymphocytes and CD68+ and CD163+-macrophages. Associations with clinicopathological variables, prognosis, and immune cell densities were further assessed. A total of 41 (33%) OSCC samples showed positive LLT1 staining in tumor cells and 55 (44%) positive LLT1 in tumor-infiltrating lymphocytes (TILs). Patients harboring tumor-intrinsic LLT1 expression exhibited poorer survival, suggesting an immunosuppressive role. Conversely, positive LLT1 expression in TILs was significantly associated with better disease-specific survival, and also an immune-active tumor microenvironment highly infiltrated by CD8+ T cells and M1/M2 macrophages. Furthermore, the combination of tumoral and stromal LLT1 was found to distinguish three prognostic categories (favorable, intermediate, and adverse; p = 0.029, Log-rank test). Together, these data demonstrate the prognostic relevance of tumoral and stromal LLT1 expression in OSCC, and its potential application to improve prognosis prediction and patient stratification.

Imposter syndrome and its associated factors in medical students in six Peruvian faculties.

OBJECTIVE: To determine the factors associated with impostor syndrome in medical students from six regions of Peru. MATERIAL AND METHODS: A multicentre, cross-sectional study was conduced on students from first to the sixth year in six Peruvian regions. Sociodemographic, academic, and psychological characteristics were included through the Depression, Anxiety, and Stress Scale-21, the Rosenberg Self-Esteem Scale and the Clance Imposter Phenomenon Scale. Generalised linear models were performed using crude and adjusted estimated prevalence ratios. RESULTS: Of 2,231 medical students, 54.3% were female and 30.6% had the impostor phenomenon. An association was found between the PI and those who suffered from depression (aPR=1.51; 95%CI, 1.27-1.79), anxiety (aPR=2.25; 95%CI, 1.75-2.90), stress (aPR=1.37; 95%CI, 1.19-1.57), and being female (aPR=1.12; 95%CI, 1.01-1.26). CONCLUSIONS: Three out of 10 medical students suffer from PI; having some level of depression, anxiety, stress, being a woman, and/or attending the fourth academic year were predisposing factors for their development.

Síndrome del impostor y sus factores asociados en estudiantes de Medicina de seis facultades peruanas

Objetivo: Determinar los factores asociados con el síndrome del impostor (IP) en estudiantes de Medicina de 6 facultades peruanas. Material y métodos: Estudio multicéntrico transversal analítico realizado en estudiantes del primer al sexto año en 6 regiones peruanas. Se incluyeron características sociodemográficas, académicas y psicológicas mediante la escala de depresión, ansiedad y estrés, la escala de autoestima de Rosenberg y la escala del Fenómeno del Impostor de Clance. Los modelos lineales generalizados se construyeron mediante razones de prevalencia estimada brutas y ajustadas. Resultados: De 2.231 estudiantes de Medicina, el 54,3% eran mujeres y el 30,6% padecía IP. Se encontró asociación entre el IP y la depresión (RPa = 1,51; IC95%, 1,27-1,79), la ansiedad (RPa = 2,25; IC95%, 1,75-2,90), el estrés (RPa = 1,37; IC95%, 1,19-1,57) y el sexo mujer (RPa = 1,12; IC95%, 1,01-1,26). Conclusiones: De cada 10 estudiantes de Medicina, 3 sufren IP; tener depresión, ansiedad o estrés, ser mujer y/o cursar el cuarto anno fueron los factores predisponentes.

Objective: To determine the factors associated with impostor syndrome in medical students from six regions of Peru. Material and methods: A multicentre, cross-sectional study was conduced on students from first to the sixth year in six Peruvian regions. Sociodemographic, academic, and psychological characteristics were included through the Depression, Anxiety, and Stress Scale-21, the Rosenberg Self-Esteem Scale and the Clance Imposter Phenomenon Scale. Generalized linear models were performed using crude and adjusted estimated prevalence ratios. Results: Of 2,231 medical students, 54.3% were female and 30.6% had the impostor phenomenon. An association was found between the PI and those who suffered from depression (aPR=1.51; 95%CI, 1.27-1.79), anxiety (aPR = 2.25; 95%CI, 1.75-2.90), stress (aPR=1.37; 95%CI, 1.19-1.57), and being female (aPR = 1.12; 95%CI, 1.01-1.26). Conclusions: Three out of 10 medical students suffer from PI; having some level of depression, anxiety, stress, being a woman, and/or attending the fourth academic year were predisposing factors for their development.

Risk factors associated with fixation-related complications in microsurgical free flap reconstruction of the mandible.

BACKGROUND: Hardware complications (loosening of screws, infection, or exposure of the plate) in mandibular reconstruction with vascularized osseous free flaps impose significant morbidity, and frequently require revision surgery. Purpose of this study was to identify possible contributing factors for hardware complications. METHODS: This is a retrospective cohort study involving case series of patients who underwent microvascular mandible reconstructions between 2000 and 2020. Patient demographics, pathological, clinical, and treatment-related factors were analyzed in univariate and multivariate analyses. RESULTS: Ninety-one patients were enrolled, encompassing 63 reconstructions with fibular free flaps, 26 reconstructions with scapular, and 2 reconstructions with iliac flaps. Rate of hardware complications and plate exposure was 14.3% and 7.7%, respectively, with a median follow-up time for extrusion of 29 months. In univariate analysis, preoperative radiotherapy (odds ratio [OR] = 6.57, p = .01), and secondary mandible reconstruction (OR = 4.3, p = .04) were significant predictors of hardware complications, and plate exposure was most frequently found in secondary reconstruction (37.5%, OR = 11.8, p = .04). Hypertension was the most commonly found comorbidity (24%), and it trended toward significance regarding plate exposure (p = .05). Only secondary mandible reconstruction was associated with osteosynthesis complications (OR = 12.53, p = .01) and plate exposure (OR = 23.86, p = .005) on multivariate analysis, while preoperative radiation therapy did not retain its relevance on plate exposure. CONCLUSION: Secondary mandible reconstructions with vascularized osseous free flaps have a higher risk of osteosynthesis complications than primary reconstructions.

Prognostic implications of preoperative systemic inflammatory markers in oral squamous cell carcinoma, and correlations with the local immune tumor microenvironment.

Purpose: The aim of this study was to investigate the prognostic significance of preoperative inflammatory markers in peripheral blood of patients with oral squamous cell carcinoma (OSCC), and to establish correlations with the infiltrate of macrophages and lymphocytes in the local immune tumor microenvironment (TME). Materials and Methods: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and systemic immune-inflammation index (SII) were retrospectively evaluated in a cohort of 348 OSCC patients, and correlated with overall (OS) and disease-specific survival (DSS). Immunohistochemical analysis of tumoral and stromal infiltration of CD8+, CD4+, FOXP3+ and CD20+ lymphocytes and CD68+ and CD163+ macrophages was performed in a subset of 119 OSCC patient samples, and correlations further assessed. Results: NLR, SII, and LMR were significantly associated with a poorer OS in univariate analysis; however, only NLR remained a significant independent predictor in the multivariate analysis (HR = 1.626, p = 0.04). NLR and SII were inversely and significantly correlated with stromal infiltration of CD8+, CD4+, and CD20+ lymphocytes. Moreover, a significant correlation between LMR was also found to significantly associate with stromal infiltration of CD8+, CD4+, and CD20+ lymphocytes, stromal CD68+ and CD163+ macrophages, and also tumoral infiltration of CD4+ and CD20+ lymphocytes. Conclusions: Preoperative NLR, SII, and LMR may serve as valuable systemic markers to predict OSCC patient survival, with NLR emerging as an independent predictor of poor OS. Moreover, strong significant correlations were exclusively observed between systemic inflammatory markers and the local stromal infiltration of lymphocytes in the TME.

Concordance between Different Criteria for Metabolic Syndrome in Peruvian Adults Undergoing Bariatric Surgery.

BACKGROUND: Metabolic Syndrome (MetS) is a clinical entity that has been linked to several non-communicable diseases. There are various consensuses to determine its presence, such as the IDF, ALAD, Harmonized, AHA/NHLBI, NCEP-ATP III or AACE criteria. However, there is currently no standardization to properly identify it. OBJECTIVE: To assess the diagnostic concordance between different criteria for MetS in Peruvian adults undergoing bariatric surgery. METHODS: We conducted a secondary analysis of the institutional database of a bariatric clinic located in Lima, Peru. We obtained data from adults between 18-59 years who underwent bariatric surgery (Roux-en-Y Gastric Bypass or Sleeve Gastrectomy). According to the Kappa coefficient, a heatplot was designed to analyze the concordance of the criteria. RESULTS: An almost perfect concordance was found between all criteria except AACE. The highest kappa coefficient (κ = 0.980) was recorded between the IDF and ALAD criteria using all the sample. Similar results were obtained when we stratified by sex. CONCLUSIONS: This study shows that, excluding the AACE, different criteria for metabolic syndrome could be used in Latino adults undergoing bariatric surgery with similar results. Given the postoperative implications, we believe that IDF and ALAD would be the best options in our population.

Hippo-YAP signaling activation and cross-talk with PI3K in oral cancer: A retrospective cohort study.

OBJECTIVES: This study aimed to investigate the clinical and prognostic relevance of the Hippo-YAP transactivators YAP1 and TAZ in oral squamous cell carcinoma, and their possible relationship with PI3K/mTOR pathway activation. MATERIALS AND METHODS: Immunohistochemical analysis of YAP1, TAZ, PIK3CA (p110α), p-AKT (Ser473), and p-S6 (Ser235) was performed in paraffin-embedded tissue specimens from 165 OSCC patients. Correlations between protein expression and clinical data were further assessed. RESULTS: YAP1 expression was detected in both cytoplasm and nucleus of tumor cells, whereas TAZ expression was only found in the nucleus. Nuclear YAP1 was significantly associated with tumor size (p = 0.03), neck lymph node metastasis (p = 0.02), TNM stage (p = 0.02), and poor differentiation (p = 0.04). Nuclear TAZ was associated with tobacco (p = 0.03) and alcohol consumption (p = 0.04), and poor tumor differentiation (p = 0.04). There was a positive significant correlation between nuclear and cytoplasmic YAP1, nuclear TAZ, p110α expression, and mTORC1 activation p-S6 (S235). Combined expression of nuclear and cytoplasmic YAP1 was prognostic in both univariate and multivariate analyses. Active nuclear YAP1 was significantly and independently associated with poor disease-specific (p = 0.005, HR = 2.520; 95% CI = 1.319-4.816) and overall survival (p = 0.015, HR = 2.126; 95% CI = 1.155-3.916). CONCLUSION: Nuclear YAP1 is an independent predictor of poor survival in oral squamous cell carcinoma.

Imaging of odontogenic keratocysts: a pictorial review.

INTRODUCTION: The aim of the present article was to review and depict the main radiological features of odontogenic keratocysts (OKCs), thus helping the differential diagnoses from other odontogenic cysts and neoplasms. EVIDENCE ACQUISITION: A review of articles published between January 2000 and October 2020 using Medline and the MeSH Term "odontogenic keratocyst" in combination with the following terms "imaging," "radiology," "panoramic radiograph," and "computed tomography," was performed. EVIDENCE SYNTHESIS: Radiographically, OKCs are well-defined unilocular or multilocular radiolucencies bounded by corticated margins. Most lesions are unilocular; instead, multilocular OKCs represent about the 30% of cases, mainly involving the posterior mandible. When, particularly in large lesions, OKCs display a multilocular presentation with adjacent satellite cysts (daughter cysts) a "soap-bubble appearance" can be recognized. DISCUSSION: Panoramic radiograph and CT still play an important role in the diagnosis and treatment planning of OKCs. Unfortunately, it may not be easy to differentiate OKCs from other odontogenic lesions, especially when they are small and unilocular. CONCLUSIONS: Histopathological findings are still necessary to obtain a definitive diagnosis.

Imposter Syndrome and its Associated Factors in Medical Students in Six Peruvian Faculties. / Síndrome del impostor y sus factores asociados en estudiantes de Medicina de seis facultades peruanas.

OBJECTIVE: To determine the factors associated with impostor syndrome in medical students from six regions of Peru. MATERIAL AND METHODS: A multicentre, cross-sectional study was conduced on students from first to the sixth year in six Peruvian regions. Sociodemographic, academic, and psychological characteristics were included through the Depression, Anxiety, and Stress Scale-21, the Rosenberg Self-Esteem Scale and the Clance Imposter Phenomenon Scale. Generalised linear models were performed using crude and adjusted estimated prevalence ratios. RESULTS: Of 2,231 medical students, 54.3% were female and 30.6% had the impostor phenomenon. An association was found between the PI and those who suffered from depression (aPR=1.51; 95%CI, 1.27-1.79), anxiety (aPR=2.25; 95%CI, 1.75-2.90), stress (aPR=1.37; 95%CI, 1.19-1.57), and being female (aPR=1.12; 95%CI, 1.01-1.26). CONCLUSIONS: Three out of 10 medical students suffer from PI; having some level of depression, anxiety, stress, being a woman, and/or attending the fourth academic year were predisposing factors for their development.

Macrophages in Oral Carcinomas: Relationship with Cancer Stem Cell Markers and PD-L1 Expression.

Tumor-associated macrophages (TAMs) can be polarized into antitumoral M1 and protumoral and immunosuppressive M2 macrophages. This study investigated the clinical relevance of TAM infiltration in oral squamous cell carcinoma (OSCC), evaluating CD68 (M1 and M2 macrophage marker) and CD163 expression (M2 macrophage marker) in the tumor nests and surrounding stroma. Immunohistochemical analysis of both stromal/tumoral CD68+ and CD163+ TAMs was performed in paraffin-embedded tissue specimens from 125 OSCC patients, and correlated with clinical data. Potential relationships with the expression of cancer stem cell (CSC) markers and PD-L1 in the tumors were also assessed. Stromal CD163+ infiltration was significantly associated with the tumor location in the tongue, and stromal and tumoral CD68+ and CD163+-infiltrating TAMs were more abundant in nonsmokers and non-alcohol-drinkers. Strikingly, this study uncovers an inverse relationship between CD68+ and CD163+ TAMs and CSC marker expression (NANOG and SOX2) in OSCC. High infiltration of CD163+ TAMs in both tumor and stroma was strongly and significantly correlated with the absence of NANOG expression. Moreover, infiltration of both CD68+ and CD163+ TAMs was also significantly associated with high tumor expression of PD-L1. Our results suggest that there is a link between TAM infiltration and immune escape in OSCC.

Depression and Abuse During Medical Internships in Peruvian Hospitals / Depresión y maltrato en internos de Medicina de hospitales peruanos

ABSTRACT Objective: To estimate the prevalence of depression and abuse and identify the associated factors in medical interns in Peruvian hospitals. Methods: We conducted a multicentre, cross-sectional and analytical study during the months of March to May 2016. We included medical interns from 18 Peruvian hospitals, in Lima and provinces. We used a survey that included sociodemographic data and a scale to measure the perception of abuse (psychological, physical and sexual). In addition, we used the Spanish version of the PHQ-9 to evaluate depression. We used Poisson regression with robust variances to calculate prevalence ratios (PRs). Results: A total of 402 medical interns participated in the study, the median age was 25 [IQR: 21-33], and 52.7% were male. Moreover, 25.4% of them suffered from depression. In the adjusted model, the variables associated with depression were age (PRa = 1.15), the number of hours they sleep per day (PRa = 1.23), being a woman (PRa = 3.33), performing the internship in a province (PRa = 0.25), studying at a public university (PRa = 0.64), living with parents (PRa = 0.65) or alone (PRa = 0.33), and having perceived some type of abuse (PRa = 1.07). Conclusions: A quarter of surveyed medical interns had depression. Early screening is necessary to identify perceived abuse and other triggering depression factors that may adversely affect work performance and overall mental health during medical internships.

RESUMEN Objetivo: Estimar la prevalencia de depresión y maltrato e identificar sus factores asociados en los internos de Medicina de los hospitales peruanos. Métodos: Estudio multicéntrico, transversal y analítico, llevado a cabo durante los meses de marzo a mayo de 2016. Conformaron la población los internos de Medicina en 18 sedes hospitalarias de Lima y provincias. Se aplicó una encuesta que incluía características sociodemográficas y una escala para medir la percepción de maltrato (psicológico, físico y sexual). Asimismo, para evaluar la depresión, se usó el cuestionario PHQ-9 en su versión en español. Se usó regresión de Poisson con varianzas robustas para calcular las razones de prevalencia (RP). Resultados: Participaron 402 internos de Medicina; la mediana de edad fue 25 [intervalo intercuartílico, 21-33] años y el 52,7% eran varones. Además, el 25,4% padecía depresión. En el modelo ajustado, las variables asociadas con padecer depresión son edad (RPa = 1,15), cuántas horas duermen durante el día (RPa = 1,23), ser mujer (RPa = 3,33), realizar el internado en provincia (RPa = 0,25), estudiar en una universidad pública (RPa = 0,64), vivir con sus padres (RPa = 0,65) o solo (RPa = 0,33) y percibir algún tipo de maltrato (RPa = 1,07). Conclusiones: La cuarta parte de los internos encuestados tenían depresión. Es necesario realizar un cribado temprano para identificar posibles maltratos percibidos y otros factores desencadenantes de depresión, y así evitar repercusiones negativas en el desempeño laboral y la salud mental general durante el internado médico.

Depression and Abuse During Medical Internships in Peruvian Hospitals.

OBJECTIVE: To estimate the prevalence of depression and abuse and identify the associated factors in medical interns in Peruvian hospitals. METHODS: We conducted a multicentre, cross-sectional and analytical study during the months of March to May 2016. We included medical interns from 18 Peruvian hospitals, in Lima and provinces. We used a survey that included sociodemographic data and a scale to measure the perception of abuse (psychological, physical and sexual). In addition, we used the Spanish version of the PHQ-9 to evaluate depression. We used Poisson regression with robust variances to calculate prevalence ratios (PRs). RESULTS: A total of 402 medical interns participated in the study, the median age was 25 [IQR: 21-33], and 52.7% were male. Moreover, 25.4% of them suffered from depression. In the adjusted model, the variables associated with depression were age (PRa=1.15), the number of hours they sleep per day (PRa=1.23), being a woman (PRa=3.33), performing the internship in a province (PRa=0.25), studying at a public university (PRa=0.64), living with parents (PRa=0.65) or alone (PRa=0.33), and having perceived some type of abuse (PRa=1.07). CONCLUSIONS: A quarter of surveyed medical interns had depression. Early screening is necessary to identify perceived abuse and other triggering depression factors that may adversely affect work performance and overall mental health during medical internships.

Tularemia: diagnosis of an unexpected oculoglandular case in a non-endemic area by universal PCR / Tularemia: diagnóstico de un caso oculoglandular inesperado en un área no endémica mediante PCR universal

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SOX2 Expression Is an Independent Predictor of Oral Cancer Progression.

Potentially malignant oral lesions, mainly leukoplakia, are common. Malignant transformation varies widely, even in the absence of histological features such as dysplasia. Hence, there is a need for novel biomarker-based systems to more accurately predict the risk of cancer progression. The pluripotency transcription factor SOX2 is frequently overexpressed in cancers, including oral squamous cell carcinoma (OSCC), thereby providing a link between malignancy and stemness. This study investigates the clinical relevance of SOX2 protein expression in early stages of oral carcinogenesis as a cancer risk biomarker, and also its impact on prognosis and disease outcome at late stages of OSCC progression. SOX2 expression was evaluated by immunohistochemistry in 55 patients with oral epithelial dysplasia, and in 125 patients with OSCC, and correlated with clinicopathological data and outcomes. Nuclear SOX2 expression was detected in four (7%) cases of oral epithelial dysplasia, using a cut-off of 10% stained nuclei, and in 16 (29%) cases when any positive nuclei was evaluated. Univariate analysis showed that SOX2 expression and histopathological grading were significantly associated with oral cancer risk; and both were found to be significant independent predictors in the multivariate analysis. Nuclear SOX2 expression was also found in 49 (39%) OSCC cases, was more frequent in early tumor stages and N0 cases, and was associated with a better survival. In conclusion, SOX2 expression emerges as an independent predictor of oral cancer risk in patients with oral leukoplakia. These findings underscore the relevant role of SOX2 in early oral tumorigenesis rather than in tumor progression.

The Emerging Role of NANOG as an Early Cancer Risk Biomarker in Patients with Oral Potentially Malignant Disorders.

NANOG, a key regulator of pluripotency and self-renewal in embryonic and adult stem cells, is frequently overexpressed in multiple cancers, including oral squamous cell carcinoma (OSCC). It has been frequently associated with poor outcomes in epithelial cancers, and recently implicated in laryngeal tumorigenesis. On this basis, we investigated the role of NANOG protein expression as an early cancer risk biomarker in oral potentially malignant disorders (OPMD), and the impact on prognosis and disease outcomes in OSCC patients. NANOG expression was evaluated by immunohistochemistry in 55 patients with oral epithelial dysplasia, and 125 OSCC patients. Correlations with clinical and follow-up data were assessed. Nuclear NANOG expression was detected in 2 (3.6%) and cytoplasmic NANOG expression in 9 (16.4%) oral dysplasias. NANOG expression increased with the grade of dysplasia. Cytoplasmic NANOG expression and the histopathological grading were significantly correlated with oral cancer risk, although dysplasia grading was the only significant independent predictor of oral cancer development in multivariate analyses. Cytoplasmic NANOG expression was also detected in 39 (31%) OSCC samples. Positive NANOG expression was significantly associated with tobacco and alcohol consumption, and was more frequent in pN0 tumors, early I-II stages. These data unveil the clinical relevance of NANOG in early stages of OSCC tumorigenesis rather than in advanced neoplastic disease. NANOG expression emerges as an early predictor of oral cancer risk in patients with OPMD.

PD-L1 Expression in Tumor Cells Is an Independent Unfavorable Prognostic Factor in Oral Squamous Cell Carcinoma.

BACKGROUND: The immune checkpoint PD-1 and its ligand PD-L1 are involved in the induction of immunological tolerance of solid tumors including oral squamous cell carcinoma (OSCC). The aim of the study was to establish the clinical and prognostic significance of PD-L1 in OSCC. METHODS: Tissue microarrays of 125 resected OSCC were stained with two different commercially available PD-L1 antibodies (clones E1L3N and 22C3), alongside PD-1 immunostaining. RESULTS: PD-L1 expression in more than 10% of tumor cells was associated with poorer survival, and established as a clinically relevant cut-off point. This relevant PD-L1 expression was detected in 10% to 15% OSCC specimens depending on the anti-PD-L1 antibody, and showed an inverse correlation with tobacco and alcohol consumption. We consistently found that PD-L1 expression was associated with tumor recurrence and lower disease-specific survival. Multivariate analysis further revealed that neck node metastasis (HR 2.304; P = 0.009) and tumor PD-L1 expression (HR 2.571; P = 0.01) were significant independent factors for poor prognosis. CONCLUSIONS: PD-L1 expression in more than 10% of tumor cells was a significant and independent factor of poor prognosis in OSCC. IMPACT: PD-L1 expression in more than 10% of tumor cells was consistently established as a clinically relevant cut-off point by using two different antibodies. Remarkably, PD-L1 expression emerges as an independent poor prognosis marker in patients with OSCC.

Distinct Expression and Clinical Significance of Zinc Finger AN-1-Type Containing 4 in Oral Squamous Cell Carcinomas.

Zinc finger AN1-type containing 4 (ZFAND4) has emerged as a promising prognostic marker and predictor of metastasis for patients with oral squamous cell carcinoma (OSCC). However, further validation is fundamental before clinical implementation. Hence, this study evaluated the expression pattern of ZFAND4 protein expression by immunohistochemistry using an independent cohort of 125 patients with OSCC, and correlations with the clinicopathologic parameters and disease outcome. Remarkably, ZFAND4 expression, while negligible in normal epithelium, exhibited two distinct expression patterns in tumors that did not overlap. A gross granular staining was characteristic of the undifferentiated cells at the invasive front of tumors, whereas the most differentiated cells located at the center of the tumor nests showed diffuse non-granular staining. ZFAND4 staining was higher in undifferentiated than in differentiated areas of tumors. High ZFAND4 expression in differentiated cells was significantly associated to well-differentiated (p = 0.04) and non-recurrent tumors (p = 0.04), whereas ZFAND4 expression in undifferentiated cells correlated with tumor location (p = 0.005). No correlations between the ZFAND4 expression and patient survival were found. These data question the clinical relevance of ZFAND4 expression as a prognostic biomarker in OSCC, and also reveal distinct ZFAND4 expression patterns depending on the differentiation areas of tumors that should be evaluated separately.

Dysregulation of Mir-196b in Head and Neck Cancers Leads to Pleiotropic Effects in the Tumor Cells and Surrounding Stromal Fibroblasts.

The miR-196 family members have been found dysregulated in different cancers. Therefore, they have been proposed as promising biomarkers and therapeutic targets. This study is the first to investigate the role of miR-196b in the development and progression of head and neck squamous cell carcinomas (HNSCC), and also the impact on the surrounding tumor microenvironment. Increased miR-196b levels were detected in 95% of primary tumors and precancerous lesions, although no significant differences were observed between non-progressing versus progressing dysplasias. Furthermore, increased levels of both miR-196a and miR-196b were successfully detected in saliva samples from HNSCC patients. The functional consequences of altered miR-196 expression were investigated in both HNSCC cell lines and cancer-associated fibroblasts (CAFs) by transfection with specific pre-miR precursors. Results showed that both miR-196a and miR-196b elicit cell-specific responses in target genes and downstream regulatory pathways, and have a distinctive impact on cell proliferation, migration and invasion. These data reveal the early occurrence and prevalence of miR-196b dysregulation in HNSCC tumorigenesis, suggesting its utility for early diagnosis and/or disease surveillance and also as a non-invasive biomarker in saliva. The pleiotropic effects of miR-196a/b in HNSCC cell subpopulations and surrounding CAFs may complicate a possible therapeutic application.

Phosphorylated ribosomal protein S6 correlation with p21 expression and inverse association with tumor size in oral squamous cell carcinoma.

BACKGROUND: The purpose of this study was to investigate the clinical relevance of phosphorylated ribosomal protein S6 (p-S6), a surrogate marker of mammalian target of rapamycin (mTOR) activation, and p21 in a series of 125 patients with oral squamous cell carcinomas (OSCCs). METHODS: Immunohistochemical analysis was performed to ascertain the phosphorylation status of p-S6 at Ser235/236 and Ser240/244, p21, and p53 protein expression. RESULTS: Expression of phosphorylated S6 protein on either serine 235/236 or serine 240/244 was detected in 83% and 88% tumors, respectively, and both of them were inversely and significantly correlated with the tumor size and local infiltration. Positive p21 expression was found in 91.5% of the cases, and was inversely correlated with tumor size. In OSCC, p21 expression correlates with p-S6 levels, a surrogate marker of mTOR activation, independently of p53 status. CONCLUSION: Expression of both p21 and p-S6 was found to inversely associate with tumor size but not survival outcomes in patients with OSCC.