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.

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.

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.

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.

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.

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.

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.

Epidermal growth factor receptor as an adverse survival predictor in squamous cell carcinoma of the penis.

Penile carcinoma (PC) is more frequent in underdeveloped countries, generally is diagnosed at an advanced stage when therapeutic options are restricted, and thus is associated with high morbidity/mortality rates. Recent studies have demonstrated clinical benefits with epidermal growth factor receptor (EGFR)-targeted therapy in patients with PC, although there is no test that provides accurate patient selection. The aim of the present study was to evaluate the prognostic value of EGFR gene and protein status in tumor samples from patients with primary penile squamous cell carcinoma. We assessed the expression of wild-type and 2 mutant EGFR isoforms (delA746-E750 and mL858R) by immunohistochemistry in 139 samples, of which 49 were also evaluated for EGFR copy number by fluorescence in situ hybridization (FISH). Positive immunohistochemical staining of wild-type and mutant EGFR was evidenced by complete and strong membranous staining. For FISH analysis, cases were considered unaltered, polysomic, or amplified, as determined by signals of the EGFR gene and chromosome 7. An independent cohort of 107 PC samples was evaluated for mutations in EGFR, KRAS, and BRAF. Protein overexpression was noted in nearly half of the cases and was associated with cancer recurrence (P=.004) and perineural invasion (P=.005). Expression of the 2 mutated EGFR isoforms was not observed. The FISH status was not associated with protein expression. Altered FISH (polysomy and gene amplification) was an independent risk factor for dying of cancer. Only 1 patient of 107 presented KRAS mutations, and no mutations of EGFR or BRAF were observed.

Perfil clínico-patológico e molecular do cancer de pênis em pacientes atendidos em um centro de referência em oncologia no nordeste brasileiro / Molecular, clinical and pathology calfeatures of patients with penile carcinoma in a cancer center from Brazilian Northeast

O carcinoma de pênis (CaPe) é um dos desafios para a saúde pública no Brasil, correspondendo a cerca de 2,1% dos tumores masculinos, com incidência maior nas regiões norte e nordeste. Principais fatores de risco são más condições de higiene, baixo padrão sócio-econômico, fimose, tabagismo, número de parceiros sexuais e infecção pelo HPV. Acometimento linfonodal é o que mais se relaciona à diminuição da sobrevida. Genes que têm papel na proliferação e regulação celular podem estar envolvidos no seu desenvolvimento e progressão tumoral. Os genes EGFR, KRAS E BRAF fazem parte da via de sinalização das proteínas quinases ativadoras de mitose (MAPK) que controlam a proliferação e a diferenciação celular. Este estudo avaliou 108 pacientes com carcinoma peniano e pesquisou o status mutacional dos genes BRAF, KRAS e EGFR, bem como expressão de c-erbB2 correlacionando-os com dados clinico-patológicos. Apenas um pacientes apresentou mutação de KRAS e outro a hiperexpressão de c-erbB-2. Carcinomas bem diferenciados se correlacionaram positivamente com a presença de coilócitos, invasão de lâmina própria e ao estágio pT1. IPE de alto risco, invasão vascular, perineural e margens positivas se correlacionaram positivamente com a recorrência. O IPE de alto risco se relacionou com menor sobrevida. Sobrevida global e livre de doença após 2 anos de seguimento foram respectivamente 93,8% e 81,0 %. Curvas de sobrevida livre de doença foram significativamente relacionada à recorrência, envolvimento nodal e IPE de alto risco

The penile carcinoma (CAPe) nowdays is one of the major problems and challenges for public health in Brazil, accounting for approximately 2.1% of all tumors of the Brazilian men, showing a higher incidence in the North and Northeast regions. The main risk factors include poor hygiene, low socioeconomic status, and phimosis, tobacco exposure, number of sexual partners and HPV infection. The presence of lymph node involvement is the most important factor related to decreased survival. Genes EGFR, BRAF and KRAS are part of the signaling pathway of mitogen-activated protein kinases (MAPK) which that control cell proliferation and differentiation. This study evaluated 108 patients with penile carcinoma and accessed the mutational status of BRAF, KRAS and EGFR in these cases, considering their clinical outcome. In our analyses, one mutation was founded in KRAS and one c-erbB2 overexpression was observed. Well-differentiated carcinomas were positively correlated to the presence of koilocytes, lamina propria invasion and to stage pT1. Conversely, high risk score prognostic index, vascular invasion, perineural invasion and positive margins were significantly correlated to recurrence. Furthermore, high risk SPI was related to a shorter survival. Overall survival and disease-free survival after 2 years of follow-up were 93,8 % and 81,0% respectively. Curves of disease-free survival, in addition, were significantly related to the recurrence status, nodal involvement and high risk SPI

Tumor de células granulares da mama sincrônico à doença de Castleman retroperitoneal: relato de caso e revisão de literatura / Granular Cell Tumor of the Breast Synchronous to Retroperitoneal Castleman’s

Introdução: O tumor de células granulares é uma neoplasia benigna rara que pode ocorrer em qualquer parte do corpo. Na mama, representa 5-6% de todos os tumores de células da granulares. Geralmente são nódulos que podem simular um carcinoma invasivo em exames de imagem. Histologicamente é caracterizado por uma proliferação de células poligonais de aspecto granular que se agrupam em ninhos, cordões ou lençóis e apresentam uma forte marcação imuno-histoquímica para a proteína S-100. A doença de Castleman é um distúrbio linfoproliferativo benigno rarode origem controverso, caracterizada pela proliferação de tecido linfoide em qualquer cadeia linfática. Clinicamente,essa doença é dividida em forma unicêntrica e multicêntrica, a cura na forma unicêntrica é possível por meio daexcisão cirúrgica, enquanto a forma multicêntrica tem um prognóstico mais reservado em longo prazo. Relato docaso: Descreveu-se o caso de uma paciente com um nódulo de mama sugestivo de carcinoma e que teve o diagnóstico de tumor de células da granulares e, em exames de estadiamento, foi encontrada uma massa em retroperitônio que,após ressecção cirúrgica, foi diagnosticada como doença de Castleman. Conclusão: Deve-se ter, como diagnóstico diferencial de tumores malignos de mama, o tumor de células granulares, devido à similaridade ao exame clínico e em exames de imagem. A doença de Castleman deve estar no diagnóstico diferencial de massas retroperitoneais.

Helicobacter pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy: an open randomized clinical trial

RACIONAL: Ainda não está estabelecida a melhor terapêutica anti-H. pylori. OBJETIVO: Avaliar a erradicação de H.pylori usando tetraciclina e furazolidona versus amoxicilina e azitromicina em terapia tríplice com lansoprazol no nordeste do Brasil. PACIENTES E MÉTODOS: Cento e quatro pacientes infectados por H. pylori, diagnosticado através do teste rápido da urease e histologia, foram selecionados aleatoriamente para receber: lansoprazol (30 mg q.d.), tetraciclina (500 mg q.i.d.), furazolidona (200 mg t.i.d.) por 7 dias (LTF; n = 52); ou lansoprazol (30 mg b.i.d.) e amoxicilina (1 g b.i.d.) por 1 semana, mais azitromicina (500 mg q.d.) nos primeiros 3 dias (LAAz; n = 52). A erradicação de H.pylori foi avaliada 3 meses após término da terapia através do teste da urease, histologia e teste respiratório usando uréia marcada com 14Carbono. RESULTADOS: A erradicação do H. pylori foi atingida em 46 de 52 (88.4%, 95% CI: 77.5%-95.1%) pacientes no grupo LTF e em 14 de 52 (26.9%, 95% CI: 16.2%-40,1%) pacientes no grupo LAAz. Na análise per-protocolo, a taxa de erradicação foi de 91.8% (95% CI: 81.4%-97.3%) e 28.5% (95% CI: 17.2%-42.3%), respectivamente no grupo de LTF e LAAz. CONCLUSÃO: O esquema com LAAz ofereceu taxas de erradicação inaceitáveis. Por outro lado, o esquema com LTF representa alternativa adequada para erradicação de H.pylori.

[Tensional and morphologic analysis of the colonic anastomosis on 10% acetic acid induced colitis, in Wistar rats, treated with 10% aroeira-do-sertão (Myracrodruon urundeuva fr. all.) aqueous extract]. / Análise tensional e morfológica da anastomose colônica na colite induzida por ácido acético a 10%, em ratos Wistar, tratados com extrato aquoso de aroeira-do-sertão a 10% (Myracrodruon urundeuva fr. all.).

PURPOSE: Verify, from a morphologic and tensional view point, the effect of the 10% aqueous extract of aroeira-do-sertão on the colonic anastomosis, during the occurrence of 10% acetic acid induced colitis, in Wistar rats. METHODS: There were used 48 Wistar rats, distributed in two groups. All animals were subjected to induction of colitis by aqueous solution of 10% acetic acid. Twenty-four hours later, the animals were subjected to laparotomy, transverse total colotomy and end-to-end anastomosis with 5-0 polypropylene. Group A (vehicle), animals treated with carboxymethylcellulose based vehicle. Group B (aroeira), animals treated with 10% aroeira aqueous extract. Both treatments were by means of enema. Groups A and B were distributed in subgroups A3, A7, A14 and A21; B3, B7, B 14 and B21, according to the foreseen euthanasia date (days 3, 7, 14 and 21). On these dates, the animals were relaparotomized, the colonic segment containing the anastomosis was ressected subjected to the pressure test and then to the, histological analysis. For the momphologic study, the slides were dyed with hematoxilin-eosine and the healing status was evaluated based on a score chart that ranked from 0 to 16. The higher the score, the better the healing. RESULTS: On the evaluation of the morphologic study, which quantifies the evolution and degree of healing, as a final result of the healing process, the group aroeira was superior to the group vehicle (p<0.05) on the twenty-first day, showing higher velocity on tissue repair that occurs by regeneration and not by fibrosis. With respect to the tension test, there was a statistically significant difference on day 3, with predominance of the group aroeira over the group vehicle (p<0.05). CONCLUSION: The 10% aroeira-do-sertão aqueous extract, has healing activity on the colonic anstomosis during the occurrence of 10% acetic acid induced colitis. It improves the resistance to tension on the colonic anastomosis zone on the 3rd day.