CLCA1 is Poorly Expressed in Stomach Adenocarcinoma and Correlates with Immune Infiltration / CLCA1 se Expresa Deficientemente en el Adenocarcinoma de Estómago y se Correlaciona con la Infiltración Inmune

SUMMARY: Calcium-activated chloride channel regulator 1 (CLCA1) is associated with cancer progression. The expression and immunologic function of CLCA1 in stomach adenocarcinoma (STAD) remain unclear. In this investigation, the expression of CLCA1 in STAD tissues and its involvement in the progression and immune response of STAD were examined using databases such as cBioPortal, TISIDB, and UALCAN. In order to validate the expression level of CLCA1 protein in gastric adenocarcinoma, thirty clinical tissue specimens were gathered for immunohistochemical staining. The findings indicated a downregulation of CLCA1 in STAD patients, which was correlated with race, age, cancer grade, Helicobacter pylori infection, and molecular subtype. Through the examination of survival analysis, it was identified that diminished levels of CLCA1 within gastric cancer cases were linked to decreased periods of post-progression survival (PPS), overall survival (OS), and first progression (FP) (P<0.05). The CLCA1 mutation rate was lower in STAD, but the survival rate was higher in the variant group. The correlation between the expression level of CLCA1 and the levels of immune infiltrating cells in STAD, as well as the immune activating molecules, immunosuppressive molecules, MHC molecules, chemokines, and their receptor molecules, was observed. Gene enrichment analysis revealed that CLCA1 may be involved in STAD progression through systemic lupus erythematosus (SLE), proteasome, cell cycle, pancreatic secretion, and PPAR signaling pathways. In summary, CLCA1 is anticipated to function as a prognostic marker for patients with STAD and is linked to the immunization of STAD.

El regulador 1 del canal de cloruro activado por calcio (CLCA1) está asociado con la progresión del cáncer. La expresión y la función inmunológica de CLCA1 en el adenocarcinoma de estómago (STAD) aún no están claras. En esta investigación, se examinó la expresión de CLCA1 en tejidos STAD y su participación en la progresión y respuesta inmune de STAD utilizando bases de datos como cBioPortal, TISIDB y UALCAN. Para validar el nivel de expresión de la proteína CLCA1 en el adenocarcinoma gástrico, se recolectaron treinta muestras de tejido clínico para tinción inmunohistoquímica. Los hallazgos indicaron una regulación negativa de CLCA1 en pacientes con STAD, que se correlacionó con la raza, la edad, el grado del cáncer, la infección por Helicobacter pylori y el subtipo molecular. Mediante el examen del análisis de supervivencia, se identificó que los niveles reducidos de CLCA1 en los casos de cáncer gástrico estaban relacionados con períodos reducidos de supervivencia posterior a la progresión (PPS), supervivencia general (OS) y primera progresión (FP) (P <0,05). La tasa de mutación CLCA1 fue menor en STAD, pero la tasa de supervivencia fue mayor en el grupo variante. Se observó la correlación entre el nivel de expresión de CLCA1 y los niveles de células inmunes infiltrantes en STAD, así como las moléculas activadoras inmunes, moléculas inmunosupresoras, moléculas MHC, quimiocinas y sus moléculas receptoras. El análisis de enriquecimiento genético reveló que CLCA1 puede estar involucrado en la progresión de STAD a través del lupus eritematoso sistémico (LES), el proteasoma, el ciclo celular, la secreción pancreática y las vías de señalización de PPAR. En resumen, se prevé que CLCA1 funcione como un marcador de pronóstico para pacientes con STAD y está vinculado a la inmunización de STAD.

Comprehensive Analysis of CLCA1 Expression, Immune Infiltration and Immune Checkpoints in Colon Adenocarcinoma / Análisis Completo de la Expresión de CLCA1, Infiltración Inmune y Puntos de Control Inmunológico en Colonadenocarcinoma

SUMMARY: Colon adenocarcinoma (COAD) is a prevalent disease worldwide, known for its high mortality and morbidity rates. Despite this, the extent of investigation concerning the correlation between COAD's CLCA1 expression and immune cell infiltration remains insufficient. This study seeks to examine the expression and prognosis of CLCA1 in COAD, along with its relationship to the tumor immune microenvironment. These findings will offer valuable insights for clinical practitioners and contribute to the existing knowledge in the field. In order to evaluate the prognostic significance of CLCA1 in individuals diagnosed with colorectal cancers, we conducted a comprehensive analysis using univariate and multivariate Cox regression models along with receiver operating characteristic curve (ROC) analysis. This study was performed on the patient data of COAD obtained from The Cancer Genome Atlas (TCGA) database. Nomograms were developed to anticipate CLCA1 prognostic influence. Furthermore, the CLCA1 association with tumor immune infiltration, immune checkpoints, immune checkpoint blockade (ICB) response, interaction network, and functional analysis of CLCA1-related genes was analyzed. We found that Colon adenocarcinoma tissues significantly had decreased CLCA1 expression compared to healthy tissues. Furthermore, the study revealed that the group with high expression of CLCA1 demonstrated a significantly higher overall survival rate (OS) as compared to the group with low expression. Multivariate and Univariate Cox regression analysis revealed the potential of CLCA1 as a standalone risk factor for COAD. These results were confirmed using nomograms and ROC curves. In addition, protein-protein interaction (PPI) network analysis and functional gene enrichment showed that CLCA1 may be associated with functional activities such as pancreatic secretion, estrogen signaling and cAMP signaling, as well as with specific immune cell infiltration. Therefor, as a new independent predictor and potential biomarker of COAD, CLCA1 plays a crucial role in the advancement of colon cancer.

El adenocarcinoma de colon (COAD) es una enfermedad prevalente a nivel mundial, conocida por sus altas tasas de mortalidad y morbilidad. Sin embargo, el alcance de la investigación sobre la correlación entre la expresión de CLCA1 de COAD y la infiltración de células inmunes sigue siendo insuficiente. Este estudio busca examinar la expresión y el pronóstico de CLCA1 en COAD, junto con su relación con el microambiente inmunológico del tumor. Estos hallazgos ofrecerán conocimientos valiosos para los profesionales clínicos y contribuirán al conocimiento existente en el campo. Para evaluar la importancia de pronóstico de CLCA1 en personas diagnosticadas con cáncer colorrectal, realizamos un análisis exhaustivo utilizando modelos de regresión de Cox univariados y multivariados junto con un análisis de la curva característica operativa del receptor (ROC). Este estudio se realizó con los datos de pacientes de COAD obtenidos de la base de datos The Cancer Genome Atlas (TCGA). Se desarrollaron nomogramas para anticipar la influencia pronóstica de CLCA1. Además, se analizó la asociación de CLCA1 con la infiltración inmunitaria tumoral, los puntos de control inmunitarios, la respuesta de bloqueo de los puntos de control inmunitarios (ICB), la red de interacción y el análisis funcional de genes relacionados con CLCA1. Descubrimos que los tejidos de adenocarcinoma de colon tenían una expresión significativamente menor de CLCA1 en comparación con los tejidos sanos. Además, el estudio reveló que el grupo con alta expresión de CLCA1 demostró una tasa de supervivencia general (SG) significativamente mayor en comparación con el grupo con baja expresión. El análisis de regresión de Cox multivariado y univariado reveló el potencial de CLCA1 como factor de riesgo independiente de COAD. Estos resultados se confirmaron mediante nomogramas y curvas ROC. Además, el análisis de la red de interacción proteína- proteína (PPI) y el enriquecimiento de genes funcionales mostraron que CLCA1 puede estar asociado con actividades funcionales como la secreción pancreática, la señalización de estrógenos y la señalización de AMPc, así como con la infiltración de células inmunes específicas. Por lo tanto, como nuevo predictor independiente y biomarcador potencial de COAD, CLCA1 desempeña un papel crucial en el avance del cáncer de colon.

The role of immunoinflammatory markers in the prognosis and resectability of pancreatic adenocarcinoma / O papel dos marcadores imunoinflamatórios no prognóstico e ressecabilidade do adenocarcinoma pancreático

ABSTRACT Background: Pancreatic adenocarcinoma has a high mortality rate. A prognostic tool is essential for a better risk stratification. The neutrophil/lymphocyte ratio and adaptations and the platelet/lymphocyte ratio seem promising for this purpose. Aim: Evaluate the prognostic value of neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, analyze the ideal cutoff values and investigate their utility in predicting resectability. Methods: Data were collected of patients with pancreatic adenocarcinoma in Hospital de Clínicas de Porto Alegre between 2003 and 2013. The studied ratios were determined by blood count collected at hospital admission and after two cycles of palliative chemotherapy. Results: Basal neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio did not have prognostic impact in survival (p=0.394, p=0.152, p=0.177 respectively). In subgroup analysis of patients submitted to palliative chemotherapy, neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio determined after two cycles of chemotherapy were prognostic for overall survival (p=0.003, p=0.009, p=0.001 respectively). The ideal cutoff values found were 4,11 for neutrophil/lymphocyte ratio (sensitivity 83%, specificity 75%), 2,8 for derived neutrophil/lymphocyte ratio (sensitivity 87%, specificity 62,5%) and 362 for platelet/lymphocyte ratio (sensitivity 91%, specificity 62,5%), Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were not able to predict resectability (p=0.88; p=0.99; p=0.64 respectively). Conclusions: Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are useful as prognostic markers of overall survival in patients with pancreatic adenocarcinoma submitted to palliative chemotherapy. Its use as resectability predictor could not be demonstrated.

RESUMO Racional: O adenocarcinoma pancreático apresenta alta taxa de mortalidade. Uma ferramenta que possa predizer adequadamente o seu prognóstico é fundamental para melhor estratificação de risco. A razão neutrófilos/linfócitos e suas adaptações e a razão plaquetas/linfócitos tem se mostrado promissores para este fim. Objetivo: Avaliar o valor prognóstico das razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos, analisar os pontos de corte mais adequados e investigar sua utilidade como fator preditivo de ressecabilidade. Métodos: Foram coletados dados de pacientes com adenocarcinoma pancreático atendidos no Hospital de Clínicas de Porto Alegre entre 2003 e 2013. As razões estudadas foram determinadas com base nos hemogramas coletados na internação e após dois ciclos de quimioterapia paliativa. Resultados: As razões neutrófilos/linfócitos basal, neutrófilos/linfócitos derivada basal e plaquetas/linfócitos basal não tiveram impacto prognóstico na sobrevida (p=0,394, p=0,152, p=0,177 respectivamente). No subgrupo submetido a quimioterapia paliativa, as razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos após dois ciclos de tratamento mostraram-se fatores prognósticos para sobrevida global (p=0,003, p=0,009 e p=0,001 respectivamente). Os pontos de corte encontrados foram 4,11 para neutrófilos/linfócitos (sensibilidade 83% e especificidade 75%), 362 para plaquetas/linfócitos (sensibilidade 91% e especificidade 62,5%) e 2,8 para neutrófilos/linfócitos derivada (sensibilidade 87% e especificidade 62,5%). As razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos não se mostraram estatisticamente significativas como preditores para ressecabilidade (p=0,88; p=0,99 e p=0,64 respectivamente). Conclusões: As razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos são úteis como marcadores prognósticos de sobrevida global em pacientes com adenocarcinoma pancreático submetidos à quimioterapia paliativa. Seu uso como preditor de ressecabilidade não foi demonstrado.

Evaluation of P53, E-cadherin, Cox-2, and EGFR protein imunnoexpression on prognostic of resected gallbladder carcinoma / Avaliação da imuno-expressão das proteínas P53, E-caderina, Cox-2 e EGFR no prognóstico do carcinoma de vesícula biliar ressecado

BACKGROUND: Gallbladder carcinoma presents a dismal prognosis. Choice treatment is surgical resection that is associated a high levels of both morbidity and mortality. Best knowledgement of prognostic factors may result a better selection of patients either for surgical or multimodal treatment. AIM: To evaluate tecidual immunoexpression of P53, E-cadherin, Cox-2, and EGFR proteins and to correlate these findings with resected gallbladder adenocarcinoma survival. METHODS: Clinical, laboratorial, surgical, and anatomopathological reports of a series of gallbladder adenocarcinoma patients were collected by individualized questionary. Total sample was 42 patients. Median of age was 72 years (35-87). There were seven men and 35 women. Lesion distribuition in according TNM state was the following: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Twenty-three patients underwent radical resection (R0), while 19 palliative surgery (R1-R2). A block of tissue microarray with neoplasic tissue of each patient was confected. It was performed evaluation of P53, E-Caderine, COX-2, and EGFR proteins imunoexpression. These findings were correlated with overall survival. RESULTS: Five-year survival was 28%. The median of global survival was eight months. Only immunoexpression of EGFR protein was considered independent variable at multivariated analysis. CONCLUSION: Final prognosis was influenced by over-expression of EGFR protein in tumoral tissue. .

RACIONAL: O carcinoma de vesícula biliar apresenta mau prognóstico. O tratamento de escolha é a ressecção cirúrgica que está associado à alta morbimortalidade. O melhor conhecimento de fatores prognósticos pode resultar em melhor seleção dos doentes para o tratamento cirúrgico e multimodal. OBJETIVOS: Avaliar a imunoexpressão tecidual das proteínas P53, E-caderina, Cox-2 e EGFR e correlacionar com a sobrevida do adenocarcinoma de vesícula biliar ressecado. MÉTODO: Os dados clínicos, laboratoriais, cirúrgicos e anatomopatológicos de uma série de doentes operados por adenocarcinoma de vesicula biliar foram coletados. A casuística total foi de 42 doentes. A mediana de idade foi de 72 anos (35-87). Foram sete homens e 35 mulheres. A distribuição da lesão de acordo com TNM foi a seguinte: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Vinte três doentes realizaram ressecção radical (R0) enquanto 19 operação paliativa (R1-R2). Um bloco de tissue microarray foi confeccionado com tecido neoplásico de cada doente. para avaliação da imunoexpressão das proteínas P53, E-Caderina, COX-2 e EGFR. Esses achados foram correlacionados com prognóstico final dos doentes. RESULTADOS: A sobrevida estimada em cinco anos foi de 28%. A mediana de sobrevida global foi de oito meses. Apenas a imunoexpressão da proteína EGFR foi considerada variável independente no prognóstico dos doentes. CONCLUSÃO: Pior prognóstico teve relação com a imunoexpressão aumentada da proteína EGFR no tecido tumoral. .

Clinical predictors of resectability of pancreatic adenocarcinoma

Identifying patient-related factors as well as symptoms and signs that can predict pancreatic cancer at a resectable stage, which could be used in an attempt to identify patients at an early stage of pancreatic cancer that would be appropriate for surgical resection and those at an unresectable stage be sparred unnecessary surgery. A retrospective chart review was conducted at a major tertiary care, university hospital in Riyadh, Saudi Arabia. The study population included individuals who underwent a computed tomography and a pancreatic mass was reported as well as the endoscopic reporting database of endoscopic procedures where the indication was a pancreatic mass, between April 1996 and April 2012. Any patient with a histologically confirmed diagnosis of adenocarcinoma of the pancreas was included in the analysis. We included patients' demographic information [age, gender], height, weight, body mass index, historical data [smoking, comorbidities], symptoms [abdominal pain and its duration, anorexia and its duration, weight loss and its amount, and over what duration, vomiting, abdominal distention, itching and its duration, change in bowel movements, change in urine color], jaundice and its duration. Other variables were also collected including laboratory values, location of the mass, the investigation undertaken, and the stage of the tumor. A total of 61 patients were included, the mean age was 61.2 +/- 1.51 years, 25 [41%] were females. The tumors were located in the head [83.6%], body [10.9%], tail [1.8%], and in multiple locations [3.6%] of the pancreas. Half of the patients [50%] had Stage four, 16.7% stages two B and three, and only 8.3% were stages one B and two A. On univariable analysis a lower hemoglobin level predicted resectability odds ratio 0.65 [95% confidence interval, 0.42-0.98], whereas on multivariable regression none of the variables included in the model could predict resectability of pancreatic cancer. A CA 19-9 cutoff level of 166 ng/mL had a sensitivity of 89%, specificity of 75%, positive likelihood ratio of 3.6, and a negative likelihood ratio of 0.15 for resectability of pancreatic adenocarcinoma. This study describes the clinical characteristics of patients with pancreatic adenocarcinoma in Saudi Arabia. None of the clinical or laboratory variables that were included in our study could independently predict resectability of pancreatic adenocarcinoma. Further studies are warranted to validate these results.

Avaliação clínica e laboratorial da trombose venosa em pacientes com câncer de pulmão / Clinical and laboratory evaluation of venous thrombosis in patients with lung cancer

INTRODUÇÃO: A trombose é um fenômeno frequente nos pacientes portadores de neoplasias e está relacionada com o prognóstico dos mesmos. No entanto, até os dias de hoje, a real incidência de trombose e os mecanismos relacionados ainda não estão totalmente elucidados. MÉTODOS: O presente estudo acompanhou, de forma prospectiva e consecutiva, 120 pacientes portadores de adenocarcinoma de pulmão em diferentes estágios da doença. Nestes pacientes foram testados ao diagnóstico e a cada 6 meses, marcadores da coagulação (TAP, PTT, fibrinogênio, D-dímero, proteína C, antitrombina, fatores (VIII e IX) e plaquetas) além de parâmetros imunológicos (presença de anticorpos anticardiolipina, anticoagulante lúpico, anti B2 glicoproteína l, níveis de interleucinas (1 e 6) e fator de necrose tumoral). Os mesmos foram acompanhados a cada 3 meses (no caso de sintomas) com pesquisa de trombose em membros inferiores e superiores (e no caso de suspeita, pesquisa de embolia pumonar). Daqueles pacientes dos quais se obteve o bloco de diagnóstico, também foi feito estudo da expressão de fator tecidual e receptores PAR1. RESULTADOS: Trombose foi um evento frequente (24% dos pacientes) e esteve relacionada com uma pior sobrevida. Em análise univariável, a presença de altos níveis de interleucina-6, fatores VIII e IX, fibrinogênio, além de presença de anticorpo anticoagulante lúpico, estiveram relacionados com o aumento de eventos trombóticos. Porém, em análise multivariável, apenas o anticoagulante lúpico manteve-se como fator de risco. Por outro lado, a presença de anticorpos anti B2 glicoproteína l do tipo IgM não só reduziu o risco de eventos trombóticos como também aumentou a sobrevida dos pacientes. A presença da expressão de fator tecidual esteve mais frequente nas fases avançadas da doença, enquanto a expressão de PAR foi maior em estados iniciais. Ambos não mostraram influenciar de forma significativa o risco de trombose e mortalidade...

INTRODUCTION: Thrombosis is a frequent event on cancer patients and are related to their prognosis. However, until now the real incidence and their mechanism are still not fully elucidated. METHODS: We studied prospectively and consecutively 120 patients with lung adenocarcinoma in different disease stages. Those patients made blood evaluation at diagnosis and each 6 month each for clotting (TAP, TPP, fibrinogen, D-dimmer, Protein C, antithrombin, platelets and clotting factors VIII and IX) than immunologic markers (anticardiolipin antibodies, lupus anticoagulant, anti B2 glicoproteín I, interleukin 1 and 6 and Tumor Necrosing Factor Levels). The same patients were submitted to limb and arms Doppler scan each 3 month to screening for thrombosis and if suspected of pulmonary embolism it was screened). From those patients of witch paraffin block of tumor biopsy were obtained, immunohistochemical analysis were made to detect tissue factor and PAR1 expression. RESULTS: Thrombosis were a frequent event (24% of patients), and were related to survival (independently if symptomatic or not). Univariable analysis showed that high levels of interleukin 6, fibrinogen, factors VIII or XI and lupus anticoagulant detection increases thrombosis risk. However in multivariable analysis, only lupus anticoagulant antibodies maintain as risk factor of thrombosis. But, despite be from antiphospholipid family, IgM anti B2 glicoproteín l decreased thrombosis risk and increase patients' survival as compared for those patients without those antibodies. Tissue factor expression was more evident on advanced stage of disease and PAR expression in early stages. However neither tissue factor nor PAR changes in a significantly manner patient's survival (however, the number of patients samples studied is small). CONCLUSION: Venous thrombosis is very frequent in lung adenocarcinoma patients. In our study, we show interaction between both systems (clotting and immunologic)...

A inter-relação das sialomucinas (antígenos Tn e Stn) com o adenocarcinoma no esôfago de Barrett / Relationship of the sialomucins (Tn and Stn antigens) with adenocarcinoma in Barrett's esophagus

OBJETIVO: O esôfago de Barrett (EB) é conseqüência do refluxo gastroesofágico crônico e considerado fator de risco para o desenvolvimento de adenocarcinoma. Estudos do muco, em especial das mucinas ácidas representadas pelas sialomucinas presentes nas células caliciformes, mostraram que na metaplasia do tipo intestinal, o epitélio do órgão pode expressar antígenos denominados Tn e Stn. Estes antígenos já foram analisados em tumores gástricos e colônicos, porém não foram encontradas referências à sua utilização no EB. Este trabalho objetivou analisar estes antígenos em doentes com EB e em adenocarcinoma associado ao EB. MÉTODOS: Foram estudados, utilizando testes imunohistoquímicos, os antígenos Tn e Stn, nas biópsias endoscópicas de 29 doentes com EB, sete com adenocarcinoma no EB, além de oito indivíduos com epitélio esofágico normal. RESULTADOS: Nas células caliciformes, foi observada positividade para Stn em 100 por cento dos casos e para Tn em 48 por cento dos casos. Nas células colunares, o Stn foi sempre negativo, enquanto o Tn foi positivo em 100 por cento dos casos. Entretanto, nos doentes com adenocarcinoma no EB, a positividade para ambos os antígenos foi de 100 por cento. Nos indivíduos normais, houve positividade para o antígeno Tn e negatividade para Stn em todos os casos (100 por cento). CONCLUSÃO: É provável que nos doentes com EB a positividade para o Tn, à semelhança do ocorrido quanto à positividade do mesmo antígeno nos portadores de adenocarcinoma, possa significar maior suscetibilidade para ocorrência futura de câncer. Assim, a pesquisa das sialomucinas poderá ser rotineiramente utilizada, contribuindo como fator prognóstico para desenvolvimento de adenocarcinoma no EB.

OBJECIVE: Barrett's esophagus (BE) is a consequence of chronic gastroesophageal reflux and is considered a risk factor for adenocarcinoma. The study of the mucus, especially acid mucins, such as the sialomucins in the goblet cells which characterize BE, showed that in intestinal metaplasia, frequent in the digestive tract, the organ's original epithelium could express Tn and Stn antigens. These antigens have already been detected in gastric and colonic tumors, however references in BE were not found. This research aimed to analyze these antigens in patients with BE and in adenocarcinoma associated with BE. METHODS: Utilizing immunohistochemistry tests, Tn and Stn antigens were studied in the endoscopic biopsies of 29 patients with BE and seven with adenocarcinoma in BE, as well as eight individuals with normal esophageal epithelium at upper digestive endoscopy.. RESULTS: The Stn antigen was positive in the goblet cells of patients with BE in 100 percent of the cases and the Tn was positive in 48 percent. In the columnar cells, Stn was always negative, while Tn was positive in 100 percent of the cases. However, in adenocarcinoma in BE, both antigens were 100 percent positive. In normal individuals, the Tn antigen was positive and the antigen Stn negative in all cases. CONCLUSION: It is probable that the BE group in which the Tn antigens in the goblet cells are positive, similarly to the same antigen in the adenocarcinoma group, might indicate a higher susceptibility for potential occurrence of cancer. In the future, trials with sialomucins could be used routinely, thereby contributing as a prognostic factor of adenocarcinoma in BE.

Morphological Feature correlation with serum tumour markers in prostatic carcinoma

To find out Gleason grades, scores and to see the correlation of these morphological features with tumour markers in prostatic carcinoma. Design: A descriptive study. Place and Duration of Study: The study was conducted at the Departments of Histopathology and Chemical Pathology, Armed Forces Institute of Pathology, Rawalpindi, over a period of one year. Materials and Fifty cases of prostatic carcinoma were studied. Gleason grades and score of tumour were determined by doing haematoxylin and eosin [H and E] staining. Pre-operative serum prostatic acid phosphatase [PAP] and prostate-specific antigen [PSA] assays were carried out in these cases. The patients seen were between 50-102 years of age with an average of 70.9 years. There were 49 cases of adenocarcinoma and 01 case of mixed adeno and transitional cell carcinoma of prostate. Twenty-eight [56%] patients had Gleason score of 5-7. Twenty-nine [58%] patients were having serum PSA levels between 10.0 ng/ml and 50.0 ng/ml. Thirteen [26%] cases showed PSA assays > 50 ng/ml. The sensitivity of PSA test was 84% in these cases. Thirty-five [70%] patients were having PAP values > 3.7 U/l [sensitivity 70%]. The Gleason grading system is a specific morphological predictor. The serum PSA showed better sensitivity and specificity with Gleason grades and scores as compared to serum PAP. The serum PAP levels showed better correlation with morphological features as compared to serum PSA

Immunoreactivity of CD99 in Stomach Cancer

CD99 is characteristically expressed in Ewing's sarcoma/primitive neuroectodermal tumor. Recently its immunoreactivity has also been reported in other tumors. However, the significance of CD99 isoforms expressed in these tumors has not been elucidated. In this study, we evaluated the expression of CD99 isoforms and its relationship with histopathologic parameters in gastric adenocarcinomas. Paraffin sections of 46 gastric adenocarcinomas were stained with an anti-CD99 monoclonal antibody, YG32. Twelve (26.1%) cases of 46 gastric adenocarcinomas showed immunoreactivity to YG32. The CD99 expression was also seen both in non-neoplastic foveolar epithelial cells and infiltrating lymphocytes. In addition, Western blot and RT-PCR analyses revealed that the type I is the predominant isoform of CD99 in non-neoplastic and neoplastic gastric tissues. The CD99 expression was usually seen in the intestinal type adenocarcinoma, while rarely in the diffuse type. The CD99 immunoreactivity decreased in MMP-2-overexpressing adenocarcinomas (p=0.028). Our results suggest that the type I is the major isoform of CD99 expressed in non-neoplastic gastric mucosa and gastric adenocarcinomas and its downregulation in gastric adenocarcinoma may be associated with cellular dedifferentiation and/or MMP-2 overexpression.

Prostate specific antigen as tumor marker: relationship with histologic grading.

PSA is emerging as the best marker in oncology and had a profound impact on all aspects of prostate cancer care. From clinically suspected prostate tumor, 395 serum samples were taken out and estimated for serum PSA. Among elevated serum PSA, 98 were correlated with histologic findings. 42(42.8%) cases were BHP among 98 cases and 78.7% had serum PSA level within 10 ng/ml. 5 patients (5.1%) had PIN histologically, 3(60%) of which had PSA level upto 10 ng/ml and 2(40%) had serum PSA upto 20 ng/ml. 51(52%) were adenocarcinoma prostate of different grades and PSA level varies from less than 10 ng/ml to more than 50 ng/ml which almost correlates with the tumor grades.

Chicken egg yolk anti-asialoGM1 immunoglobulin (IgY): an inexpensive glycohistochemical probe for localization of T-antigen in human colorectal adenocarcinomas.

A egg yolk polyclonal IgY has been prepared by immunization of white leghorn chickens with small unilamellar liposomal asialoGM1. The newly prepared anti-asialoGM1 IgY has been characterized to be specific toward the terminal carbohydrate moiety of asialoGM1, and has no cross reactivity to its sialylated counterpart (ganglioside, GM1) as evidenced by immunochromatographic studies. General glycohistochemical methods along with antigen specific lectin and immunohistochemical staining using anti-asialoGM1 IgY were used to study the expression of Thomsen-Friedenreich (T-) disaccharide antigen in human colorectal adenocarcinoma tissues. The expression of T-antigen in colon cancer tissue was detected by two T-disaccharide specific probes, chicken anti-T-yolk antibody (IgY) and Artocarpus integrifolia lectin (AIL) and was found to be more pronounced in both the secreted mucin as well as the cytoplasmic mucin deposits. These immunochemical detection methods for T-antigen showed a weaker correlation with other glycostaining methods using, alcian-blue/periodic acid-Schiff (AB-PAS) and high iron diamine (HID). However, a general enzymatic staining for galactose and galactosamine containing glycoconjugates, by galactose oxidase-Schiff method, showed a good correlation with T-antigen detection. While the T-beta specific anti-asialoGM1 could localize T-antigen in 11 of 13 (84%) human colorectal adenocarcinoma tissue sections tested, the T-alpha specific AIL could localize the T-antigen in only 6 of the tissues (46%). These observations confirm previously reported findings, of the prevalence of T-beta conformation in colon cancer, that binds significantly more with the anti-asialoGM1 IgY than with the T-alpha specific AIL. Hence, both anti-T IgY and the AIL immunohistochemical probes may have useful diagnostic value because of the ease of preparation and cost effectiveness, but the T-beta specific anti-asialoGM1 probe (IgY) would have a better prognostic value in colon adenocarcinomas.

Expresión de la proteína del gen supresor de tumores p53 en el carcinoma de próstata / Expression of the supressor gene protein of p53 tumors in prostatic carcinoma

El cáncer de la próstata es una de las neoplasias más frecuentes en hombres mayores de 50 años. La mutación y expresión del gen supresor de tumores p53 ha sido demostrado en la carcinogénesis de múltiples neoplasias y en alrededor del 40 por ciento de los cánceres de la próstata. El objeto de este trabajo es determinar la frecuencia de la expresión del gen p53 en el carcinoma prostático. Se estudia la expresión de la proteína p53 en 35 carcinomas prostáticos mediante la técnica de inmunohistoquímica con anticuerpo monoclonal. Los pacientes se distribuyeron por etapas clínicas: Etapa A = 4 casos; Etapa B = 5 casos; Gleason entre 4 y 7 y el 16 por ciento entre 8 y 10. El promedio de edad fue 70,7 años (límites 53-85 años). No se observó tinción positiva en ninguno de los controles ni en los tumores en etapas A y B. Se observó tinción positiva de la proteína del gen p53 en 11 de los 35 casos (31,4 por ciento), 17 por ciento en los en Etapa C y un 64,2 por ciento tumores en los en Etapa D (p = 0,01). No se observó diferencia respecto del índice de Gleason aun cuando los tumores mejor diferenciados presentaron menor positividad. Nuestros resultados muestran que la proteína del gen supresor de tumores p53 no guarda relación con el índice de Gleason y sólo se observa en tumores avanzados, especialmente en la Etapa D, y su determinación puede contribuir significativamente a una mejor evaluación preoperatoria de los pacientes

Expresión inmunohistoquímica de la oncoproteína p53 en adenomas y adenocarcinomas del intestino grueso / Immunohistochemical expression of p53 oncoprotein in large bowel adenomas ans carcinomas

Material and methods: A random sample of 28 large bowel adenomas and 44 carcinomas was studied. Determination of p53 protein was made with an immunohistochemical method using monoclonal antibodies. Patients were followed for a mean of 36 months (range 1 to 100 months). Results: p53 immunostaining was obtained in one adenoma (3.5 percent) and in 18 carcinomas (41 percent, p = 0.01). There were no differences in survival during follow up, between cancer patients that expressed or did not express p53 protein. Conclusions: About half of colorectal tumors have immunohistochemical expression of p53 protein, as published abroad. We did not find a prognostic value for this protein in our sample

Primary adenocarcinoma of the urinary bladder--a case report with review of literature.

Primary adenocarcinoma of the urinary bladder is a rare neoplasm. We present the clinicopathological and immunohistochemical analysis of a case in a 50 year old male. The histogenesis of the tumour and a review of literature is also discussed.

Modulación de la angiogenesis inducida por linfocitos por proteinas de la matriz extracelular / Modulation of angiogenesis induced by lymphocytes by extracellular matrix proteins

La neovascularización es uno evento importante en el desarrollo y crecimiento tumoral. La liberación de células tumorales en la circulación no se observa en la fase avascular del crecimiento tumroal. Los linfocitos de ratones portadores de tumor son capaces de inducir una respuesta angiogénica cuando se inoculan intradérmicamente en la piel de animales singenéicos. Esta respuesta recibe el nombre de SLIA. En este trabajo se estudia proteínas presentes en la matriz extracelular, colágeno y fibronectina (FN) pueden modificar la respuesta antiogênica inducida por linfocitos de ratones portadores de tumor S13. El tratamiento de los linfocitos con FN o con el péptido Gly. Arg. Glyp. Asp. inhibió la angiogénesis. Por el contrario el colágeno y el péptido Gly. Arg. Gly. Asp. Ser no modificaron la respuesta neovascular inducida por los linfocitos de portadores de tumor

Localization of carcinoembryonic antigen in uterine cervical neoplasia.

Tissues for 74 uterine cervical lesions including 64 invasive squamous cell carcinomas, 4 adenocarcinomas and 6 cervical intraepithelial neoplasia (CIN) were studied by peroxidase-antiperoxidase (PAP) method for presence of carcinoembryonic antigen (CEA). CEA was absent in normal squamous and endocervical epithelium. The antigen was demonstrated in all the cases of CIN (100%) and in 48 invasive carcinomas (70.6%). A heterogeneous pattern of staining was noted in different cases and also within a tumour. None of the 6 endometrial carcinomas showed CEA reactivity while all sections from endocervical carcinomas were positive for CEA. Carcinoembryonic antigen may be a useful tumour marker in the diagnosis of cervical neoplasia and helpful in differentiating endocervical carcinoma from endometrial carcinoma.

Value of tissue carcinoembryonic antigen in patients with colorectal carcinoma.

The tumours of 55 patients with colorectal carcinoma were evaluated for tissue carcinoembryonic antigen (CEA) by immunoperoxidase staining. It was shown that 33/35 patients with increased preoperative serum CEA levels above 5 ng/ml had positive tissue CEA. The other 17/20 patients who had serum CEA levels less than 5 ng/ml could be demonstrated CEA in tissue. The results of tissues CEA were compared with their preoperative serum CEA levels in the pathologic grading, histologic type and staging of cancer. It was found that tissue CEA was more sensitive than serum CEA and was correlated with serum CEA in all respects. The finding in this study suggests that tissue CEA should be performed along with preoperative serum CEA in all patients suspected of having colorectal carcinoma. The postoperative serum CEA should be determined serially in the patients who have more than 5 ng/ml serum CEA and/or tissue CEA positive although their preoperative serum CEA is less than 5 ng/ml.

Pre-operative and post-operative evaluation of circulating immune complexes in patients with gastric adenocarcinoma.

Circulating immune complexes (CICs) in the sera of patients with histologically proven adenocarcinoma of stomach were sequentially studied. Serial CICs levels, quantitated using a sensitive method F(ab')2 anti-C3 ELISA, were measured before surgery and in a post-operative follow up. CICs could be detected in 85% of the patients pre-operatively, while ten days after surgery positivity decreased to 71%. Thirty days after surgery, the mean CIC levels decreased significantly and positivity fell to 46%. The results indicate that removal of primary tumor mass results in a sharp decline of CIC levels.

Immunological status of patients in carcinoma head and neck.

The cell mediated immune response in 45 patients of cancer, head and neck was evaluated by various parameters and compared with 20 control cases. (DNCB) Dinitrochlorobenzene cutaneous reactivity in vivo was compared with T lymphocytes, estimated as active rosette forming cells (ARFC) and Total rosette forming cells (TRFC) in peripheral blood. The ratio of TRFC/ARFC was studied in various histological subtypes of cancer head and neck. Lymphocytic infiltration around tumor mass was correlated with peripheral blood lymphocyte (PBL), ARFC and TRFC levels in blood. Significant difference was noted in the level of peripheral blood lymphocytes (PBL). TRFC and ARFC between control cases and cancer patients. There was a marked increase in all three parameters i.e. PBL, TRFC, ARFC (P less than 0.001) and a positive DNCB reaction in Adenocarcinoma of nasopharynx, thyroid and salivary gland and a significant decrease in Squamous cell Carcinoma of oral cavity and larynx (p less than 0.001) associated with impaired DNCB sensitivity. These parameters serve as an assessment of the degree of immune reactivity of the host to the malignant tumours.