Deficiency in infiltration of CD8/CD3 positive lymphocytes and macrophages plays a role in lip carcinogenesis: an immunohistochemical study.

OBJECTIVE: To evaluate the immunoexpression profile for CD8, CD3, CD20 and CD68 in the process and carcinogenesis of Carcinoma of the vermilion lip. METHODS: Average cell count with positive expression for CD3, CD8, CD20 and CD68. The CD8/CD3 ratio calculated in the region was based on the percentage of positive cells in a total of malignant cells. Kruska-Wallis/Dunn, Mann-Whitney and Spearman correlation tests (SPSS, p < 0.05) were used. RESULTS: In the Aquitic Cheilitis samples, there was an increase in intraepithelial CD8+ and CD68+. In LSCCs, there was an increase in peritumoral and intratumoral CD3+, CD8+, CD20+ and CD68+ cells. In peritumoral LSCC, CD3+ and CD8+ showed a direct correlation (p = 0.004), and CD68+ and CD8+ (p = 0.017). In the intraepithelial region, CD8+ correlated with CD20+ (p = 0.014) and CD68+ (p = 0.013). In the CAs, CD3 (p < 0.001) and CD8 (p = 0.025) correlated intraepithelial and subepithelial. In LSCC CD3+ (p = 0.002), CD8+ (p = 0.001) and CD68+ (p = 0.030) had intra and peritumoral correlation. CONCLUSION: CD68+ is the first interacting cell with the greatest capacity to migrate to the tumor and interact with CD3, CD8 and CD20. Apparently, CD20 affects perineural invasion. LEVEL OF EVIDENCE: Level 2.

Deficiency in infiltration of CD8/CD3 positive lymphocytes and macrophages plays a role in lip carcinogenesis: an immunohistochemical study

Abstract Objective To evaluate the immunoexpression profile for CD8, CD3, CD20 and CD68 in the process and carcinogenesis of Carcinoma of the vermilion lip. Methods Average cell count with positive expression for CD3, CD8, CD20 and CD68. The CD8/CD3 ratio calculated in the region was based on the percentage of positive cells in a total of malignant cells. Kruska-Wallis/Dunn, Mann-Whitney and Spearman correlation tests (SPSS, p< 0.05) were used. Results In the Aquitic Cheilitis samples, there was an increase in intraepithelial CD8+ and CD68+. In LSCCs, there was an increase in peritumoral and intratumoral CD3+, CD8+, CD20+ and CD68+ cells. In peritumoral LSCC, CD3+ and CD8+ showed a direct correlation (p= 0.004), and CD68+ and CD8+ (p= 0.017). In the intraepithelial region, CD8+ correlated with CD20+ (p= 0.014) and CD68+ (p= 0.013). In the CAs, CD3 (p< 0.001) and CD8 (p= 0.025) correlated intraepithelial and subepithelial. In LSCC CD3+ (p= 0.002), CD8+ (p= 0.001) and CD68+ (p= 0.030) had intra and peritumoral correlation. Conclusion CD68+ is the first interacting cell with the greatest capacity to migrate to the tumor and interact with CD3, CD8 and CD20. Apparently, CD20 affects perineural invasion. Level of evidence: Level 2.

Mu and Kappa opioid receptor immunolabeling indicates the prognosis of oropharyngeal squamous cell carcinoma: A cross-sectional observational study.

BACKGROUND: Opioids are the most effective drugs currently available for cancer pain management. The administration of morphine, in addition to its analgesic effect, can alter tumor development. OBJECTIVE: To characterize the immunoexpression of opioid receptors µ and κ in oropharyngeal squamous cell carcinoma, and correlate it with prognostic factors, proliferation markers, and cell death. MATERIALS AND METHODS: A retrospective, cross-sectional observational study was carried out with 50 patients diagnosed at Haroldo Juaçaba Hospital. Sociodemographic, clinicopathological, and overall survival data were collected, and excisional biopsies were taken for immunohistochemistry using tissue microarrays for opioid receptors µ and κ, Ki-67, and caspase-3. Immunolabeling was evaluated and correlated with other variables using Mann-Whitney, Kruskal-Wallis, Spearman correlation, log-rank (Mantel-Cox), and Cox regression tests. RESULTS: Immunoexpression of opioid receptors µ and κ, Ki-67, and caspase-3 was significantly higher in p16+ and p16- primary tumors and lymph node metastases than in surgical resection margins. The overall survival of patients with p16- tumors was 57.53 ± 8.43 months and that of patients with p16+ tumors was slightly higher at 75.92 ± 11.14 months. Multivariate analysis showed that the expression of opioid receptors µ and κ in the nucleus was directly associated with a lower and higher risk of death, respectively. CONCLUSION: We found increased expression of opioid receptors µ and κ in tumor tissues. The nuclear expression of opioid receptors µ and κ influences overall survival and may be a prognostic factor of oropharyngeal squamous cell carcinoma.

Prognostic factors and overall survival in a 15-year followup of patients with malignant salivary gland tumors: a retrospective analysis of 193 patients / Fatores prognósticos e sobrevida global em um seguimento de 15 anos de pacientes com tumores malignos da glândula salivar: uma análise retrospectiva de 193 pacientes

Abstract Introduction Malignant tumors of the salivary glands are uncommon pathological entities, representing less than 5% of head and neck neoplasms. The prognosis of patients with malignant tumors of the salivary glands is highly variable and certain clinical factors can significantly influence overall survival. Objective To analyze the clinicopathologic and sociodemographic characteristics that influence survival in patients with malignant tumors of the salivary glands Methods This retrospective study analyzed sex, age, race, education level, tumor location, tumor size, lymph node involvement, distant metastasis, margin status, treatment type, marital status, method of health care access and 15-year overall survival in 193 patients with malignant tumors of the salivary glands. The X², log-rank Mantel-Cox, multinomial regression and Cox logistic regression tests were used (SPSS 20.0,p < 0.05). Results The most common histological types were adenocarcinoma (32.1%), adenoid cystic carcinoma (31.1%) and mucoepidermoid carcinoma (18.7%). The 15-year overall survival rate was 67.4%, with a mean of 116 ± 6 months. The univariate analysis revealed that male sex (p = 0.026), age > 50 years (p = 0.001), referral origin from the public health system (p = 0.011), T stage (p = 0.007), M stage (p < 0.001), clinical stage (p < 0.001), compromised surgical margins (p = 0.013), and chemotherapy (p < 0.001) were associated with a poor prognosis. Multivariate analyses also showed that age > 50 years was independently associated with a poor prognosis (p = 0.016). The level of education was the only factor more prevalent in older patients (p = 0.011). Conclusion Patients with malignant tumors of the salivary glands older than 50 years have a worse prognosis and an independent association with a low education level.

Resumo Introdução Os tumores malignos das glândulas salivares são entidades patológicas incomuns, representam menos de 5% das neoplasias de cabeça e pescoço. O prognóstico dos pacientes com tumores malignos das glândulas salivares é altamente variável e alguns fatores clínicos podem influenciar significativamente a sobrevida global. Objetivo Analisar as características clinicopatológicas e sociodemográficas que influenciam a sobrevida em pacientes com tumores malignos das glândulas salivares. Método Este estudo retrospectivo analisou sexo, idade, etnia, nível de escolaridade, localização do tumor, tamanho do tumor, envolvimento linfonodal, metástase distante, margens, tipo de tratamento, estado civil, método de acesso à assistência médica e sobrevida global em 15 anos de 193 pacientes com tumores malignos das glândulas salivares. Foram usados os testes X2, log-rank Mantel-Cox, regressão multinomial e regressão logística de Cox (SPSS 20.0, p < 0,05). Resultados Os tipos histológicos mais comuns foram adenocarcinoma (32,1%), carcinoma adenoide cístico (31,1%) e carcinoma mucoepidermoide (18,7%). A taxa de sobrevida global em 15 anos foi de 67,4%, com média de 116 ± 6 meses. A análise univariada revelou que sexo masculino (p = 0,026), idade > 50 anos (p = 0,001), origem de referência do sistema público de saúde (p = 0,011), estádio T (p = 0,007), estádio M (p < 0,001)), estágio clínico (p < 0,001), margens cirúrgicas comprometidas (p = 0,013) e quimioterapia (p < 0,001) foram associados a um prognóstico ruim. As análises multivariadas também mostraram que a idade > 50 anos foi associada independentemente a um prognóstico ruim (p = 0,016). O nível de escolaridade foi o único fator mais prevalente em pacientes idosos (p = 0,011). Conclusão Pacientes com tumores malignos das glândulas salivares acima de 50 anos apresentam pior prognóstico e associação independente com baixo nível de escolaridade.

Prognostic factors and overall survival in a 15-year followup of patients with malignant salivary gland tumors: a retrospective analysis of 193 patients.

INTRODUCTION: Malignant tumors of the salivary glands are uncommon pathological entities, representing less than 5% of head and neck neoplasms. The prognosis of patients with malignant tumors of the salivary glands is highly variable and certain clinical factors can significantly influence overall survival. OBJECTIVE: To analyze the clinicopathologic and sociodemographic characteristics that influence survival in patients with malignant tumors of the salivary glands METHODS: This retrospective study analyzed sex, age, race, education level, tumor location, tumor size, lymph node involvement, distant metastasis, margin status, treatment type, marital status, method of health care access and 15-year overall survival in 193 patients with malignant tumors of the salivary glands. The X², log-rank Mantel-Cox, multinomial regression and Cox logistic regression tests were used (SPSS 20.0,p < 0.05). RESULTS: The most common histological types were adenocarcinoma (32.1%), adenoid cystic carcinoma (31.1%) and mucoepidermoid carcinoma (18.7%). The 15-year overall survival rate was 67.4%, with a mean of 116±6 months. The univariate analysis revealed that male sex (p = 0.026), age > 50 years (p=0.001), referral origin from the public health system (p=0.011), T stage (p= 0.007), M stage (p< 0.001), clinical stage (p< 0.001), compromised surgical margins (p= 0.013), and chemotherapy (p< 0.001) were associated with a poor prognosis. Multivariate analyses also showed that age > 50 years was independently associated with a poor prognosis (p= 0.016). The level of education was the only factor more prevalent in older patients (p= 0.011). CONCLUSION: Patients with malignant tumors of the salivary glands older than 50 years have a worse prognosis and an independent association with a low education level.

Immunoexpression of HSPA9 and CUL2 in prostatic tissue and adenocarcinoma.

CUL2 plays a crucial role in proteolysis by preserving the balance between normal growth and uncontrolled proliferation. HSPA9 safeguards the integrity of protein interactions and supports cellular homeostasis. In carcinomas, HSPA9 and CUL2 appear to protect neoplastic cells from internal and external damage. In prostate tumors they are apparently associated with increased risk of unfavorable outcomes, but information remains scarce. In this study we evaluated CUL2 and HSPA9 expression in neoplastic and non-neoplastic prostate tissue and Gleason pattern 3 and 4 adenocarcinoma to identify associations with ISUP prognostic groups and postoperative disease progression. The records of 636 radical prostatectomy patients were reviewed retrospectively and microarrays were mounted with paraffin-embedded adenocarcinoma and non-neoplastic tissue. We evaluated the ability of HSPA9 and CUL2 to predict postoperative PSA outcomes, response to adjuvant/salvage therapy and systemic disease. HSPA9 and CUL2 were diffusely expressed. HSPA9 expression was associated with increased risk of high-grade adenocarcinoma, while HSPA9 and CUL2 were associated with biochemical failure after salvage therapy. In conclusion, HSPA9 and CUL2 were highly expressed in prostate tissue, especially in neoplastic cells. HSPA9 and CUL2-positive Gleason pattern 3 adenocarcinoma was more likely to be associated with Gleason pattern 4 or 5, while HSPA9 and CUL2-positive Gleason pattern 4 adenocarcinoma was less likely to belong to ISUP groups 1 and 2. Staining for HSPA9 and CUL2 can help identify patients at increased risk of recurrence after salvage therapy.

PMS2: a potential prognostic protein marker in oral squamous cell carcinoma / PMS2: un potencial marcador proteico de pronóstico en el carcinoma oral de células escamosas

Background: An increase in oral squamous cell carcinoma (OSCC) cases was observed despite the reduction inexposure to classic risk factors. Although the exact cause of this trend remains unknown, epigenetic factors couldbe contributing to an increased occurrence of these tumors. This study aims to assess the influence of PMS2 pro-tein immunoexpression on the prognosis of patients with OSCC.Material and Methods: This study comprised 76 cases of OSCC treated between 2011 and 2016. Immunohisto-chemical staining for PMS2 was performed. For evaluation, 10 fields per histological section were photographed ata 400x magnification and positively-stained cells were counted with Image J. Mann-Whitney and Kruskal-Wallistests were used to compare the immunolabeling pattern with the clinical-pathological and prognostic characteris-tics. Survival analysis was performed with Chi-square, Long-Rank Mantel-Cox and Cox regression tests (p<0.05).Results: An overexpression of PMS2 was observed in N0/1 tumors and in oral cancers found in unusual locations.In patients ≤60 years of age, high levels of PMS2 (>60%; p=0.041) were associated with low survival (p=0.029).In multivariate analysis, surgery combined with chemotherapy (p=0.030) and high PMS2 immunoexpression(p=0.042) significantly increased the risk of death for ≤60 years old patients Conclusions: The findings of this study indicate that PMS2 can be a potential prognostic protein marker in OSCCpatients 60 years of age and younger.(AU)

Prognostic factors on surgically and non-surgically treated oral squamous cell carcinoma: Advances in survival in fifteen years of follow up.

BACKGROUND: Retrospectively to evaluate the influence of radiochemotherapy (RCT) in the treatment of surgically and non-surgically treated Oral Squamous Cell Carcinoma (OSCC). MATERIAL AND METHODS: We analysed 934 patients treated in Hospital Haroldo Juaçaba (2000-2014; 15 years of study) by extraction of data type of cancer, localization of tumour, sex, age, race, education level, risk factors (smoking and alcohol use), year of diagnosis, TNM stage, therapeutic approach, health system used (public or private) and overall survival (OS). Surgically and non-surgically treated OSCC were compared by chi-square and Fisher's exact tests, and their prognostic factors were analysed by log-rank Mantel-Cox plus Cox regression tests (SPSS 20.0, p<0.05). RESULTS: Non-surgically treated OSCC patients had a lower OS than surgically treated OSCC patients (p<0.001), but an increase in OS was shown in both groups. Although the 2010-2014 period (p=0.003), education level (p=0.032), tongue/mouth floor/palate localization (p=0.023) and TNM stage (p<0.05) were important in non-surgically treated OSCC OS, the major prognostic factors were node metastasis (p=0.003) and non-use of RCT (p=0.039) (multivariate analysis). In surgically treated OSCC patients, higher OS was shown in the 2010-2014 period (p<0.001), females (p=0.012), non-drinkers (p=0.011), non-smokers (p=0.009) and those with lower TNM stage (p<0.05), but the major prognostic factor was the 2010-2014 period (p=0.004) (multivariate analysis), which was directly associated with an increase in RCT indication (p<0.001). CONCLUSIONS: The increase in RCT improved the OS in this large cohort of surgically and non-surgically treated OSCC patients. Key words:Mouth neoplasms, neck, radiotherapy, drug therapy, combination.

Prognostic value of FUS immunoexpression for Gleason patterns and prostatic adenocarcinoma progression.

BACKGROUND: Risk assessment is important when planning treatment for prostatic adenocarcinoma. Gleason score is a strong predictor of disease progression, despite the possibility of mismatches between biopsy and prostatectomy. In order to increase the accuracy of Gleason scores, several markers have been proposed. One of these, FUS (fused in sarcoma), plays a role in RNA processing, chromosome stability and gene transcription. PATIENTS AND METHODS: Non-neoplastic tissue and Gleason pattern 3, 4 and 5 adenocarcinoma samples were submitted to tissue microarrays. Gleason pattern 3 and 4 were compared to the final Gleason score. We also conducted univariate and multivariate tests to probe the association between FUS expression in adenocarcinoma samples and outcome: biochemical persistence and biochemical recurrence (separately or pooled as biochemical progression), biochemical failure after salvage radiotherapy, and systemic progression. RESULTS: Our cohort consisted of 636 patients. Non-neoplastic tissue stained less frequently (36.5%) than neoplastic tissue (47.4%), with expression increasing from Gleason pattern 3 towards pattern 5. FUS-positive Gleason pattern 3 was significantly associated with final Gleason scores >6 (HR = 1.765 [1.203-2.589]; p = 0.004). Likewise, FUS-positive Gleason pattern 4 was significantly associated with final Gleason scores ≥7 (4 + 3). The association between FUS positivity and biochemical persistence and recurrence observed in the univariate analysis was not maintained in the multivariate analysis (HR = 1.147 [0.878-1.499]; p = 0.313). CONCLUSION: Non-neoplastic tissue was less frequently FUS-positive than neoplastic tissue. FUS positivity in Gleason pattern 3 and 4 increased the risk of high grade adenocarcinoma and was associated with clinical/laboratory progression in the univariate, but not in multivariate analysis.

Mismatch Repair Proteins in Oropharyngeal Squamous Cell Carcinoma: A Retrospective Observational Study.

Cases of oropharyngeal squamous cell carcinoma are on the rise and the disease now ranks as the most common human papillomavirus-related cancer. Although risk factors have been extensively discussed in the literature, the role of the DNA mismatch repair system remains unanswered. To evaluate the impact of the DNA mismatch repair (MMR) protein immunostaining on the tumor progression and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). This retrospective observational study comprised 50 cases of OPSCC. Immunohistochemistry for MSH2, MSH6, PMS2, MLH1, Ki67, p16 and caspase-3 was performed. The expression of these proteins was assessed in surgical resection margins, primary tumor (PT), and lymph node metastasis (LNM) of p16+ and p16- OPSCC. Clinical-pathological involvement in immunostaining was evaluated with Kruskal-Wallis/Dunn or Mann-Whitney test, Wilcoxon test and Spearman's correlation. Overall survival (OS) was analyzed with Log-Rank Mantel-Cox and Cox regression. MSH6 and caspase-3 showed high expression in PT (p16+ and p16 -) and in LNM (p16+ and p16-), and high levels of MSH2 were found in LNM (p16+ and p16 -). An imbalance in MutSα also was observed. PMS2 and caspase-3 expression was associated with poor survival in p16- OPSCC and, in multivariate analysis, MSH2, MSH6 and MLH1 had the poorest prognostic impact in p16+ OPSCC. MMR protein immunostaining is involved in OPSCC progression, dissemination and prognosis. The overexpression of MMR proteins as a response to increased DNA mismatch caused by cell proliferation and MSH2, MSH6 and MLH1 proteins might constitute a prognostic marker in p16+ OPSCC.

Histórico de Consumo de Álcool como Fator Preditivo de Sobrevida em Pacientes com Carcinoma de Células Escamosas de Boca e Orofaringe: Follow-up de 15 Anos / Alcohol Consumption History as a Predictive Factor of Survival in Patients with Mouth and Oropharyngeal Squamous Cell Carcinoma: Follow-up of 15 Years / Historia del Consumo de Alcohol como Factor Predictivo para la Supervivencia en Pacientes con Carcinoma de Células Escamosas Bucales y Orofaríngeas: Seguimiento de 15 Años

Introdução: O carcinoma de células escamosas é o tumor de maior importância na região de cabeça e pescoço, em razão da sua incidência e mortalidade. Sabe-se que fatores como consumo de álcool estão relacionados à diminuição da sobrevida de tumores tanto estimulando a progressão tumoral como causando comorbidades importantes, sendo um fator relevante para estudo. Objetivo: Avaliar a influência do histórico de álcool em características clinicoprognósticas de pacientes com carcinoma de células escamosas de boca e orofaringe (CCEBO). Método: Estudo de coorte, retrospectivo, no qual 156 prontuários de pacientes etilistas e 78 prontuários de pacientes não etilistas com CCEBO diagnosticados no Hospital Haroldo Juaçaba, em Fortaleza, Ceará, foram avaliados, entre 2000 e 2014, para análise de dados como idade, sexo, raça, localização do tumor, estadiamento TNM, tratamentos realizados e sobrevida em 15 anos por meio dos testes X², Long-Rank e modelos de regressão multinomial e de Cox (SPSS 20,0; p<0,05). Resultados: Houve maior prevalência de homens entre os pacientes etilistas (p<0,001), com tumores T3-T4 (p=0,003), linfonodos positivos (p=0,006) que realizaram tratamentos paliativos (p<0,001) e menor prevalência abaixo de 65 anos (p<0,001), quando havia histórico familiar de câncer (p=0,043). A sobrevida dos pacientes etilistas foi menor (p=0,040) e os fatores que diminuíram a sobrevida de maneira independente foram sexo masculino (p=0,042), estadiamento T3-T4 (p=0,004), metástase linfonodal (p=0,012), idade >65 anos (p=0,035) e localização na língua (p=0,042). O sexo masculino foi independentemente associado ao etilismo (p<0,001). Conclusão: O álcool é um fator de prognóstico em pacientes com CCEBO, mostrando maior prevalência em pacientes T3-T4 e, assim, influenciando negativamente no prognóstico.

Introduction: Squamous cell carcinoma is the most important tumor in the head and neck region, due to its incidence and mortality. It is known that factors as alcohol consumption are related to the decrease of the survival of tumors, either stimulating tumor progression or causing considerable comorbidities, being an important study factor. Objective: Evaluate the influence of alcohol history on clinical and prognostic characteristics of patients with mouth oropharynx squamous cell carcinoma (MOSCC). Method: A retrospective cohort study in which 156 charts of alcoholic patients and 78 medical charts of non-alcoholic patients with MOSCC diagnosed at Haroldo Juaçaba Hospital in Fortaleza, state of Ceará were evaluated between 2000 and 2014 for data analysis such as age, gender and race, tumor location, TNM staging, treatments performed and 15-year survival through X², Long-Rank and Cox and multinomial regression models (SPSS 20.0; p <0.05). Results: Men were more prevalent among alcoholic patients (p <0.001), with T3/4 tumors (p = 0.003), positive lymph nodes (p = 0.006) who submitted to palliative treatments (p<0.001) and lower prevalence under 65 years (p <0.001), when there was a family history of cancer (p = 0.043). The survival of alcoholic patients was lower (p = 0.040) and the factors that independently reduced survival were male sex (p = 0.042), T3-T4 staging (p = 0.004), lymph node metastasis (p = 0.012), age> 65 years (p = 0.035) and tumor in the tongue (p = 0.042). Male sex was independently associated with alcohol consumption (p<0.001). Conclusion: Alcohol is a prognostic factor in patients with MOSCC, showing a higher prevalence in T3-T4 patients and, thus, negatively influencing the prognosis.

Introducción: El carcinoma de células escamosas es el tumor de mayor importancia en la región de cabeza y cuello, debido a su incidencia y mortalidad. Se sabe que factores como el consumo de alcohol están relacionado con la disminución de la supervivencia de tumores tanto estimulando la progresión tumoral, como provocando comorbilidades considerables, siendo un factor de estudio importante. Objetivo: Evaluar la influencia del historial del consumo de alcohol en las características clínicas-pronósticas de pacientes con carcinoma de células escamosas oral y orofaringe (CCEOO). Método: Estudio retrospectivo en el que se evaluaron 156 registros médicos de pacientes consumidores de alcohol y 78 de pacientes no alcohólicos con CCEOO diagnosticados en el Hospital Haroldo Juaçaba, en Fortaleza, Ceará, entre 2000 y 2014, para el análisis de datos como edad, sexo raza, escolaridad, los antecedentes familiares, vínculo matrimonial, registro en el servicio, ubicación del tumor, clasificación de TNM, los tratamientos realizados y la supervivencia durante 15 años a través de las pruebas X² Long-Rank y modelos de regresión multinomial y de Cox (SPSS 20.0; p<0,05). Resultados: Hubo una mayor prevalencia de hombres entre pacientes alcohólicos (p<0,001), con tumores T3-T4 (p=0,003), ganglios linfáticos positivos (p=0,006), y realizó tratamientos paliativos (p<0,001) y menor prevalencia en paciente menores de 65 años (p <0,001); cuando se presentaron antecedentes familiares de cáncer (p=0,043). La supervivencia de los pacientes alcohólicos fue menor (p=0,040); y los factores que disminuyeron la supervivencia de forma independiente fueron hombres (p=0,042); estadificación t3-t4 (p=0,004); metástasis a ganglios linfáticos (p=0,012); edad > 65 años (p=0,035); localización de la lengua (p=0,042). El sexo masculino se asoció independientemente con el consumo de alcohol (p<0,001). Conclusión: El alcohol define el pronóstico en pacientes con CCEOO, muestra una mayor prevalencia en pacientes con T3-T4, por lo tanto, influye negativamente en el pronóstico.

Role of Inflammatory Markers in Prognosis of Oral Squamous Cell Carcinoma.

BACKGROUND: This estudie evaluated the immunostaining of cytokines in oral carcinoma, in tissue of margin of surgical resecate (MSR) and metastatic lymph nodes, as well as their role in patient prognosis. METHODS: A retrospective study was carried out in patients with oral squamous cell carcinomas, and sociodemographic and clinical-pathological data were evaluated. In addition, surgical site analysis of the patients was conducted by immunohistochemistry, using a tissue microarray for inflammatory (Tumor Necrosis Factor-alpha, Interleukin-1beta, Interleukin-6, interleukin-10), transcription NF-kappa B and CD68 markers. Immunoexpression was assessed qualitatively and quantitatively using ImageJ software, and data were correlated with the prognostic factors and patient survival rates. RESULTS: There was a greater immunoexpression of inflammatory and CD68 cytokines in primary tumour and lymph node metastasis than in MSR. In a multinomial logistic regression model, patients with low education (p = 0.041) and a high histoscore for TNF-α (p = 0.021) showed a survival rate of 15.64 (95% CI = 1.13-217.24) and 6.81 (95% CI = 1.02-105.96). CONCLUSION: Therefore, despite there is an increased immunoexpression of cytokines in the primary tumour, only TNF-α was the inflammatory cytokine that influenced the survival of patients with oral cancer.

Smoking History Decreases Survival in Patients with Squamous Cell Carcinoma of the Mouth: A Retrospective Study with 15 Years of Follow-up.

Background: The purpose of this study was to evaluate the influence of smoking history on the clinical-pathological, sociodemographic and prognostic characteristics of patients with oral squamous cell carcinoma (SCC). Materials and Methods: A retrospective cohort study was carried out with the records of 136 smokers with SCC and 68 nonsmokers with oral SCC who were diagnosed and treated at Haroldo Juaçaba Hospital (2000-2014). Data on patient sex, age, race, education level, tumor location, tumor size, lymph node involvement, distant metastasis, treatment type, marital status, method of health care access (public or private health systems) and overall survival (15 years) were analyzed by the X² test, Mantel-Cox tests and multinomial and Cox logistic regression models (SPSS 20.0, p <0.05). Results: Smoking history was directly associated with male sex (p <0.001), low levels of education (p = 0.001), tumors of the mouth and palate (p = 0.001), stage T3/4 tumors (p = 0.014), lymph node metastasis (N+) (p = 0.024), palliative treatment (p = 0.024) and receiving health care through the public health system (p = 0.006), with education level being the only independently associated factor (p = 0.039). Lower survival was observed in patients who were smokers (p = 0,002), with low levels of education (p = 0.001), who had stage T3/4 tumors (p = 0.004), with N+ (p = 0.021), and had received palliative treatment (p = 0.002). Age (>65 years old, p = 0.015) and T staging (T3/4, p = 0.033) decreased the survival of SCC patients regardless of the other factors. Conclusions: Smoking history had an independent association with low education level and a history of alcoholism, and survival was negatively associated with older age and larger tumor size, which were more prevalent in smokers.

Evaluation of the diagnostic potential of CD1a immunohistochemistry for visceral leishmaniasis.

Visceral Leishmaniasis is a public health problem caused by protozoans of the genus Leishmania. K39 serological test is commonly used in the initial investigation, with high specificity, but variable sensitivity. Amastigotes can be identified by optical microscopy, however, the differential diagnosis with cellular debris or other intracellular parasites is necessary. Recent studies have raised the possibility of using immunohistochemistry in the diagnosis of visceral leishmaniasis with labeling of amastigotes by the anti-CD1a antibody. This retrospective study was based on 38 samples from patients with visceral leishmaniasis whose diagnoses were confirmed by myelogram and/or k39 testing, aside from positive (N=13) and negative biopsies (N=25), 2 samples from patients with false positive biopsies for visceral leishmaniasis and 8 samples from patients with histoplasmosis diagnosis. The histological slides were evaluated for the presence of amastigotes and their Modified Ridley Parasitic Index. The samples were submitted to immunohistochemical reactions using the anti-CD1a antibody with MTB1 and O10 clones. Immunohistochemical reactions with MTB1 and O10 clones had low sensitivity in this study. However, all bone marrow samples were previously decalcified with nitric acid which is probably a deleterious treatment for immunohistochemical reactions in this site. Excluding these samples, we obtained 58.33% sensitivity and 100% specificity with the MTB1 clone. Despite the intermediate sensitivity, the immunohistochemistry for the CD1a marker with clone MTB1 can be useful in the differential diagnosis of visceral leishmaniasis, helping to discriminate leishmania amastigotes from other pathogens with similar morphology and cellular debris in different samples, except in bone marrow biopsies previously decalcified with nitric acid.

PanCD44 Immunohistochemical Evaluation in Prostatectomies from Patients with Adenocarcinoma.

INTRODUCTION: CD44 has been proposed as a prognostic marker and a stem cell marker but studies in patients with prostate cancer have yielded inconsistent results. PATIENTS AND METHODS: Patients submitted to radical prostatectomy between 2008 and 2013 at a university hospital were followed with biannual serum PSA tests to determine the biochemical recurrence (BR). Archived paraffin blocks with neoplastic and nonneoplastic tissue were evaluated immunohistochemically for a panCD44 and MYC. RESULTS: Sixty-nine patients completed follow-up and were included. CD44 positivity was observed in inflammatory cells (42%), nonneoplastic epithelium (39.7%), and neoplastic tissue (12.3%). In nonneoplastic tissues staining was observed in basal and luminal cells with the morphology of terminally differentiated cells. In neoplastic tissues, CD44 negativity was correlated with higher Gleason scores (Rho = -0.204; p = 0.042) and higher preoperative serum PSA levels when evaluated continuously (p = 0.029). CD44 expression was not associated with tumor stage (p = 0.668), surgical margin status (p = 0.471), or BR (p = 0.346), nor was there any association between CD44 and MYC expression in neoplastic tissue (p = 1.0). CONCLUSION: In the bulk of cells, the minority of cancer stem cells would not be detected by immunohistochemistry using panCD44. As a prognostic marker, its expression was weakly correlated with Gleason score and preoperative PSA level, but not with surgical margin status, tumor stage, or BR.

The association among HER2, MET and FOXP3 expression and tumor regression grading in gastric adenocarcinoma.

Although the introduction of the perioperative chemotherapy on the management of gastric cancer has improved patients survival, heterogeneity of clinical outcomes has been evidenced in parallel to different histopathological regression pattern of gastric cancer cells. Thus, this study evaluated the tumor regression grading (TRG) in a series of post-treatment gastric tumors and its associations with HER2, MET, and FOXP3 expression. Material of 54 gastric cancer samples was available for TRG evaluation and immunohistochemistry. We found that total and subtotal pathologic response were significantly associated to the intestinal subtype (p = 0.04) and that well-differentiated tumors were significantly correlated with total or partial response (p = 0.019). Although not associated with the TRG, FOXP3 expression in gastric tumors was associated to poorly differentiated tumors (p = 0.03), to the diffuse and mixed subtypes together (p = 0.04) and to the presence of vascular infiltration (p = 0.04), while HER2 overexpression was associated to better differentiated cases (p = 0.04) and to the absence of vascular infiltration (p = 0.02). MET expression, however, showed no association with the analyzed clinicopathological factors. This study highlights the role of tissue differentiation on pathological response to neoadjuvant chemotherapy in gastric cancer and shows no impact between FOXP3, HER2 and MET expression in terms of TRG.

Mammary hibernoma: A case report of a rare disease / Hibernomamamário: relato de caso de uma doença rara

Abstract Mammary hibernomas are extremely rare benign tumors composed of brown fat cells, with only five cases previously reported in the literature. We report the case of a 42- year-old female patient with a painless growing mass in her right breast. A partial mastectomy was performed, and the diagnosis of hibernoma was confirmed by the histological features and the immunohistochemical profile. Although hibernoma is a benign tumor, its main differential diagnoses include aggressive lesions, making the accurate diagnosis essential to provide adequate care to the patient.

Resumo Hibernomas mamários são tumores benignos extremamente raros compostos por gordura marrom, com apenas cinco casos previamente relatados na literatura. Relatamos o caso de uma paciente do sexo feminino, de 42 anos de idade, apresentando- se com uma massa indolor em sua mama direita. Realizou-se uma mastectomia parcial e o diagnóstico de hibernomamamário foi confirmado pelo padrãomorfológico e pelo perfil imuno-histoquímico. Embora hibernomas constituamneoplasias benignas, seus principais diagnósticos diferenciais incluem lesões agressivas, sendo o diagnóstico acurado extremamente importante para o correto manejo clínico do paciente.

Mammary Hibernoma: A Case Report of a Rare Disease.

Mammary hibernomas are extremely rare benign tumors composed of brown fat cells, with only five cases previously reported in the literature. We report the case of a 42-year-old female patient with a painless growing mass in her right breast. A partial mastectomy was performed, and the diagnosis of hibernoma was confirmed by the histological features and the immunohistochemical profile. Although hibernoma is a benign tumor, its main differential diagnoses include aggressive lesions, making the accurate diagnosis essential to provide adequate care to the patient.

Hibernomas mamários são tumores benignos extremamente raros compostos por gordura marrom, com apenas cinco casos previamente relatados na literatura. Relatamos o caso de uma paciente do sexo feminino, de 42 anos de idade, apresentando-se com uma massa indolor em sua mama direita. Realizou-se uma mastectomia parcial e o diagnóstico de hibernoma mamário foi confirmado pelo padrão morfológico e pelo perfil imuno-histoquímico. Embora hibernomas constituam neoplasias benignas, seus principais diagnósticos diferenciais incluem lesões agressivas, sendo o diagnóstico acurado extremamente importante para o correto manejo clínico do paciente.

Immunohistochemical Expression of the Tumor Suppressor Protein p16INK4a in Cervical Adenocarcinoma.

Objective To evaluate the diagnostic utility of the p16ink4a protein expression as a marker for adenocarcinoma of the cervix. Methods In a cross-sectional study, p16ink4a expression was evaluated in 30 cervical biopsies from patients diagnosed with invasive adenocarcinoma from 2 reference clinics in Brazil, and compared with 18 biopsies of endocervical polyps (control cases). The performance of the tests for p16ink4a was evaluated using a conventional contingency table, and the Kappa (κ) index was used to evaluate the agreement of the marker with the tissue diagnosis. Results In total, 66% of the invasive adenocarcinoma cases were positive for p16ink4a. All of the adenomatous polyps cases used as negative controls were shown to be negative for p16ink4a. The marker showed a high sensitivity and a high negative predictive value. The Kappa index was good for p16ink4a (κ = 0.6). Conclusion Considering the strong association between the p16ink4a marker and the cervical adenocarcinoma, its use represents an important tool for reducing incorrect diagnoses of adenocarcinoma and thereby avoiding overtreatment.

Histopathological regression of gastric adenocarcinoma after neoadjuvant therapy: a critical review.

As the perioperative chemotherapy has been widely implemented on the management of gastric cancer patients, heterogeneity of clinical outcomes has been evidenced in parallel to different histopathological regression pattern of gastric cancer cells. Tumor histological response to preoperative therapy has been graded by various systems in order to categorize the amount of regressive changes induced by chemotherapy in relation to residual tumor. In this context, tumor regression grading (TRG) systems might provide important prognostic information as the variety of tumor response may imply on different clinical outcomes with impact in survival rates. Moreover, gastric cancer behavior varies enormously upon individual factors such as histological classification and tumor anatomic site of involvement that have been shown to affect the TRG interpretation. On the other hand, some studies have assessed the role of molecular markers as a predictor of tumor response to neoadjuvant chemotherapy in terms of TRG. Thus, the aim of this review is to evaluate how TRG has been interpreted in gastric cancer, discuss their clinical and prognostic relevance and also address the molecular markers involved in this process.