Maintenance treatment in advanced HER2-negative gastric cancer.

Survival for patients with advanced gastric cancer (GC) remains poor. Systemic chemotherapy which has reached a plateau stays the standard first-line (1L) treatment for advanced human epidermal growth-factor receptor 2 (HER2)-negative GC. To maximize the benefit of 1L treatment, the concept of maintenance treatment is constantly being explored. In advanced HER2-negative GC, current clinical guidelines do not recommend a standard maintenance therapy strategy. In addition to the monotherapy maintenance with fluorouracil after 4-6 cycles of 1L chemotherapy, some agents that are active against novel targets have been evaluated in clinical trials for maintenance treatment. Whereas most of these trials do not reach their primary endpoints, they open new horizons for the 1L treatment of advanced HER2-negative GC. Therefore, we reviewed the clinical trials in the field of maintenance treatment in advanced HER2-negative GC and discussed some of the problems in clinical trials.

THE CANONICAL WNT PATHWAY IN GASTRIC CARCINOMA.

BACKGROUND: It is believed that the Wnt pathway is one of the most important signaling involved in gastric carcinogenesis. AIM: To analyze the protein expression of canonical and non-canonical Wnt pathways in gastric carcinoma. METHOD: The immunohistochemistry was performed in 72 specimens of gastric carcinomas for evaluating the expression of Wnt-5a, FZD5, GSK3ß, axin, CK1, ubiquitin, cyclin D1 and c-myc. RESULTS: There were significant differences for cytoplasm and nucleus ubiquitin for moderately and well differentiated tumors (p=0.03) and for those of the intestinal type of the Lauren classification (p=0.03). The absence of c-myc was related to Lauren's intestinal tumors (p=0.03). Expression of CK1 in the cytoplasm was related to compromised margin (p=0.03). Expression of cyclin D1 protein was more intense in male patients (p=0.03) There was no relation of the positive or negative expression of the Wnt-5a, FZD5, GSK3 and Axin with any clinicopathological variables. CONCLUSION: The canonical WNT pathway is involved in gastric carcinoma.

The canonical wnt pathway in gastric carcinoma / Via canônica do wnt no carcinoma gástrico

ABSTRACT Background : It is believed that the Wnt pathway is one of the most important signaling involved in gastric carcinogenesis. Aim : To analyze the protein expression of canonical and non-canonical Wnt pathways in gastric carcinoma. Method : The immunohistochemistry was performed in 72 specimens of gastric carcinomas for evaluating the expression of Wnt-5a, FZD5, GSK3β, axin, CK1, ubiquitin, cyclin D1 and c-myc. Results : There were significant differences for cytoplasm and nucleus ubiquitin for moderately and well differentiated tumors (p=0.03) and for those of the intestinal type of the Lauren classification (p=0.03). The absence of c-myc was related to Lauren's intestinal tumors (p=0.03). Expression of CK1 in the cytoplasm was related to compromised margin (p=0.03). Expression of cyclin D1 protein was more intense in male patients (p=0.03) There was no relation of the positive or negative expression of the Wnt-5a, FZD5, GSK3 and Axin with any clinicopathological variables. Conclusion: The canonical WNT pathway is involved in gastric carcinoma.

RESUMO Racional : Acredita-se que a via Wnt é uma das mais importantes da sinalização envolvidas na carcinogênese gástrica. Objetivos : Analisar a expressão das proteínas das vias Wnt canônicas e não-canônicas no carcinoma gástrico e relacionar sua expressão com as variáveisclinicopatológicas. Método : Foram coletadas 72 amostras de carcinoma gástrico, e áreas representativas do tumor foram selecionadas para o Tissue Microarray. Imunoistoquímica foi realizada para avaliar a expressão de Wnt-5a, FZD5, GSK3β, axina, CK1, ubiquitina, ciclina D1 e c-myc. Resultados : Houve diferenças significativas para a expressão de ubiquitina no citoplasma e núcleo para tumores moderadamente e bem diferenciados (p=0,03) e para aqueles do tipo intestinal da classificação de Lauren (p=0,03). A expressão negativa da proteína c-myc no citoplasma foi relacionada aos tumores intestinais de Lauren (p=0,028). A expressão positiva de CK1 no citoplasma das células neoplásicas foi relacionada a tumores com margens cirúrgicas livre de envolvimento neoplásico (p=0,03). A expressão positiva da proteína ciclina D1 foi maior nos tumores dos homens (p=0,03). Não houve relação da expressão positiva ou negativa das proteínas Wnt-5a e FZD5 no citoplasma ou núcleo com quaisquer variáveis clinicopatológicas. O mesmo foi observado para GSK3β e Axin. Conclusões : A relação da expressão das proteínas da via canônica com as variáveis epidemiológicas e tumorais sugere sua participação na carcinogênese gástrica. Por outro lado, a ausência da relação das expressões das proteínas da via não-canônica sugere sua não participação na carcinogênese gástrica.

[Primary gastric choriocarcinoma: case report]. / Coriocarcinoma gástrico primario: reporte de caso.

Primary gastric choriocarcinoma (PGC) is an extremely rare and highly invasive tumor with rapid hematogenous spread. We present the case of a 57-year-old female patient who started with hematemesis and progressive episodes of melena, weight loss and epigastralgia. It is derived from the National Institute of Neoplastic Diseases where gastroscopy and biopsy are performed. Histological analysis reported pattern suggestive of PGC; that was confirmed by immunohistochemical analysis for human chorionic gonadotrophin and fetal alpha protein. Subsequently, the patient underwent a radical D2 gastrectomy with splenic preservation and tail of the pancreas preservation. Unfortunately, her evolution was not favorable and died due to the progression of the disease.

Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer.

Gastric cancer is one of the most aggressive malignancies affecting humankind. With almost a million cases globally, it sits in fifth position in terms of incidence, and third in terms of mortality. The progression of this disease is slow, with prolonged and sequential precancerous stages including chronic gastritis, intestinal metaplasia, dysplasia, and finally gastric cancer. Here we used the iTRAQ approach combined with high-resolution mass spectrometry analysis to describe the spectrum of the gastric cancer cascade. Biopsies from three stages: chronic gastritis, intestinal metaplasia, and gastric adenocarcinoma, were selected for analysis by quantitative proteomics. We identified and reported quantitative data for 3914 different proteins quantified with high confidence, uncovering pathways and processes dysregulated between the different stages. Intestinal metaplasia is characterized by the down-regulation of ribosomal proteins, with overexpression of cell survival proteins such as GSTP1 and EPCAM. The transformation to gastric cancer involves overexpression of the DNA replication and the spliceosome pathways. The impairment of mitochondrial pathways was correlated with down-regulation of SIRT3 and SIRT5, and overexpression of enzymes supporting the glycolytic phenotype, such as HK3 and PCK2. Several proteins found dysregulated during the progression of gastric cancer have potential to be used as specific biomarkers and/or therapeutic targets.

Coriocarcinoma gástrico primario: reporte de caso / Primary gastric choriocarcinoma: case report

El coriocarcinoma gástrico primario (CGP) es un tumor extremadamente raro, altamente invasivo y de rápida diseminación hematógena. Presentamos el caso de una paciente de 57 años que inicia con cuadro de hematemesis y, progresivamente, se le suman episodios de melena, baja de peso y epigastralgia. Es derivada al Instituto Nacional de Enfermedades Neoplásicas en donde se le realizan gastroscopía y biopsia. Así, el análisis histológico reportó patrón sugestivo para CGP; el cual se confirmó al realizarle a la paciente los estudios por imágenes necesarios y llevar a cabo el análisis inmunohistoquímico para gonadotrofina coriónica humana y alfa feto proteína. Posteriormente, a la paciente se le realiza una gastrectomía radical D2 con preservación esplénica y de cola de páncreas. Lamentablemente, su evolución no fue favorable y fallece por la progresión de la enfermedad.

Primary gastric choriocarcinoma (PGC) is an extremely rare and highly invasive tumor with rapid hematogenous spread. We present the case of a 57-year-old female patient who started with hematemesis and progressive episodes of melena, weight loss and epigastralgia. It is derived from the National Institute of Neoplastic Diseases where gastroscopy and biopsy are performed. Histological analysis reported pattern suggestive of PGC; that was confirmed by immunohistochemical analysis for human chorionic gonadotrophin and fetal alpha protein. Subsequently, the patient underwent a radical D2 gastrectomy with splenic preservation and tail of the pancreas preservation. Unfortunately, her evolution was not favorable and died due to the progression of the disease.

[Immunohistochemical assessment of HER2 expression in gastric cancer. A clinicopathologic study of 93 cases]. / Evaluación por inmunohistoquímica de la expresión del HER2 en cáncer gástrico. Estudio clínico-patológico de 93 casos.

BACKGROUND: Gastric cancer in Mexico is ranked third in both males and females. Most patients present clinically with advanced disease and treatment options are sparse. HER2 overexpression in gastric cancer is related to poor outcome. Immunohistochemical testing for HER2 is becoming the standard of care for guiding adjuvant treatment of gastric cancer with trastuzumab. OBJECTIVES: To determine the frequency of HER2 overexpression in patients with gastric cancer in the Hospital de Oncología del Centro Médico Nacional, Siglo XXI and its association with other histopathological findings. MATERIAL AND METHODS: Patients with gastric cancer who underwent surgery between March 12, 2006-August 31, 2011, were enrolled in this retrospective study. Diagnosis was confirmed by review of slides and immunohistochemistry with anti-HER2 antibody was performed. Scoring was done by Hoffman scoring system. Medical records were evaluated. RESULTS: Ninety-three patients were included in the study, with 43 (46.2%) male and 50 (53.7%) female patients. The median age was 64 years. HER2-positive tumours were identified in 6 patients (6.45%) and located most frequently in the proximal stomach. There was no difference in HER2 overexpression in relation to age, gender or histologic type. CONCLUSION: In our study, about 7% of patients with gastric cancer were HER2-positive on immunohistochemistry.

Association between HER2 status in gastric cancer and clinicopathological features: a retrospective study using whole-tissue sections.

BACKGROUND: Gastric cancer is usually diagnosed in an advanced stage of disease and treatment options are sparse. Trastuzumab was recently approved for metastatic or locally advanced carcinomas arising in the stomach or in the gastroesophageal junction in patients with HER2-positive tumors. However, data on the frequency of HER2-positive cases among Brazilian patients are limited. Our aim was to characterize HER2 protein and gene status in a series of Brazilian patients with gastric cancer and to evaluate its association with clinicopathological data. METHODS: Histological slides from 124 primary gastrectomies were reviewed and their pathological reports were retrieved from the files at a Brazilian university hospital. Automated immunohistochemistry for HER2 was performed on whole-tissue sections from each tumor. HER2-equivocal cases by immunohistochemistry were submitted to automated dual in situ hybridization for gene amplification evaluation. HER2 status was confronted with clinicopathological parameters in order to assess statistically significant associations. RESULTS: Immunohistochemistry analysis revealed that 13/124 cases (10.5 %) were HER2 positive (3+), 10/124 cases (8.1 %) were equivocal (2+) and 101/124 cases (81.4 %) were negative, being 7 cases 1+. None of the equivocal cases showed gene amplification. The overall HER2 positivity rate was 10.5 %. There was an association between HER2 expression and Laurén's intestinal histological subtype (P = 0.048), well to moderately differentiated tumors (P = 0.004) and presence of lymphovascular invasion (P = 0.031). No association was found between HER2 status and tumor topography. CONCLUSIONS: Confronted with data published by other authors, the lower percentage of HER2-positive cases found in our series might be partially explained by the lower frequency of tumors arising at the gastroesophageal junction in comparison with distal gastric carcinomas in Brazilian patients. This could also account for the lack of statistically significant association between HER2 status and tumor topography in our study.

La "cultura de la sobrevivencia" y la salud pública internacional en América Latina: la Guerra Fría y la erradicación de enfermedades a mediados del siglo XX / The "culture of survival" and international public health in Latin America: the Cold War and the eradication of diseases in the mid-twentieth century

Este artículo analiza las principales campañas promovidas por agencias internacionales y organismos nacionales de salud dirigidas a erradicar enfermedad infecciosas en el ámbito rural latinoamericano de los años 1940 y 1950. Las dimensiones políticas del periodo han sido estudiadas pero todavía se ha prestado poca atención a sus dimensiones sanitarias. Este trabajo propone el concepto de "cultura de la sobrevivencia" para explicar los problemas de la salud pública oficial de Estados con políticas sociales limitadas que no permitieron el ejercicio de la ciudadanía. La salud pública, como parte de esta cultura de la sobrevivencia, buscaba ser una solución temporal sin enfrentarse a los problemas sociales que originaban las infecciones y dejó un legado en la salud pública de la región.

This article analyzes the main campaigns run by international agencies and national health bodies to eradicate infectious diseases in rural Latin America in the 1940s and 1950s. The political dimensions of the period have been studied but there has been little attention as yet to the health dimensions. This article proposes the concept of a "culture of survival" to explain the official public health problems of states with limited social policies that did not allow the exercise of citizenship. Public health, as part of this culture of survival, sought a temporary solution without confronting the social problems that led to infections and left a public health legacy in the region.

IMP3 expression in gastric cancer: association with clinicopathological features and HER2 status.

BACKGROUND: The aim of this study was to evaluate the expression of IMP3, an independent poor prognostic factor for many cancers, and its association with clinicopathological features and HER2 status. METHODS: Gastrectomy specimens from 106 patients were evaluated by immunohistochemistry and fluorescence in situ hybridization. RESULTS: HER2 overexpression was found in 4.71 % of the samples. A negative association was observed between HER2 overexpression and grade of differentiation. No association was observed between HER2 overexpression and status of surgical margins, vascular invasion, perineural invasion, nodal metastasis and depth of invasion. Among all specimens of gastric cancer, 67.92 % were positive for IMP3. Expression of IMP3 was significantly higher in specimens with vascular invasion, perineural invasion, nodal metastasis and higher depth of invasion. HER2 overexpression was detected in only 5.55 % of IMP3 positive specimens. CONCLUSIONS: IMP3 expression was frequently observed in gastric cancer and was associated with poor prognostic clinicopathological features. A survival benefit with HER2 therapy should be expected for the minority of patients with IMP3 positive specimens. Studies should be conducted to evaluate the response to HER2 therapy of gastric cancer expressing IMP3.

STAG2 expression in oral cancer and potentially malignant lesions.

Oral cancer is a world health problem, and one of the highest incidence rates of oral cancer worldwide occurs in Brazil. STAG2 is part of the cohesin complex which is responsible for sister chromatid cohesion. STAG2 loss of expression was reported in a range of tumors, and STAG2 loss was found to cause chromosomal instability and aneuploidy in cancer cells. On the basis of these findings, we investigated STAG2 expression in oral cancer and potentially malignant lesions. We investigated STAG2 immunoexpression in oral cancer, lip cancer, oral leukoplakia, and actinic cheilitis, including complete clinical information. Normal oral mucosa samples were included as normal controls. STAG2 protein was highly expressed in all samples. We further tested STAG2 expression in gastric adenocarcinomas and glioblastomas, as these tumor types were previously shown to lose STAG2 expression. We found homogenous expression of STAG2 by these tumor cells. Our results suggest that STAG2 loss of expression is not a common event in oral carcinogenesis.

Lesiones gástricas en pacientes infectados con Helicobacter pylori: expresión de RAGE (receptor de productos de glicosilización avanzada) y otros inmunomarcadores / Expression of RAGE in Helicobacter pylori infested gastric biopsies

Background: Inflammation is a common phenomenon present in gastric mucosa of patients infected with H. pylori. Activation of the RAGE/multiligand axis is thought to be a relevant factor in cancer-mediated inflammation. RAGE is a membrane receptor, belonging to the immunoglobulin family, and the over-expression of RAGE has been associated with increased invasiveness and metastasis generation in different types of cancer, including gastric cancer. Furthermore recent experiences show that the use of its soluble form (sRAGE) or silencing of the gene coding for this receptor could provide therapeutic benefits in cancer. Aim: To evaluate the immunohistochemical expression of RAGE, MUC-1, β-Catenin free and phosphorylated, Cyclin-D1 and GSK3 in gastric biopsy specimens infected with H. pylori. Material and Methods: Immunohistochemical analysis was carried out in gastric biopsies from 138 patients: 55 with inflammatory injury (no atrophic gastritis), 42 with pre-cancerous conditions (atrophy or intestinal metaplasia) and 41 with dysplastic lesions or in situ adenocarcinoma. Results: There was a high rate of positive RAGE expression in the three groups of biopsies. Biopsies with dysplasia or in situ carcinoma had a significantly higher percentage of RAGE expression than the other groups of biopsies. Conclusions: The increased RAGE expression reported in both dysplasia and incipient cancer support the role of the multiligand/RAGE axis in gastric carcinogenesis.

[Expression of RAGE in Helicobacter pylori infested gastric biopsies]. / Lesiones gástricas en pacientes infectados con Helicobacter pylori: expresión de RAGE (receptor de productos de glicosilización avanzada) y otros inmunomarcadores.

BACKGROUND: Inflammation is a common phenomenon present in gastric mucosa of patients infected with H. pylori. Activation of the RAGE/multiligand axis is thought to be a relevant factor in cancer-mediated inflammation. RAGE is a membrane receptor, belonging to the immunoglobulin family, and the over-expression of RAGE has been associated with increased invasiveness and metastasis generation in different types of cancer, including gastric cancer. Furthermore recent experiences show that the use of its soluble form (sRAGE) or silencing of the gene coding for this receptor could provide therapeutic benefits in cancer. AIM: To evaluate the immunohistochemical expression of RAGE, MUC-1, ß-Catenin free and phosphorylated, Cyclin-D1 and GSK3 in gastric biopsy specimens infected with H. pylori. MATERIAL AND METHODS: Immunohistochemical analysis was carried out in gastric biopsies from 138 patients: 55 with inflammatory injury (no atrophic gastritis), 42 with pre-cancerous conditions (atrophy or intestinal metaplasia) and 41 with dysplastic lesions or in situ adenocarcinoma. RESULTS: There was a high rate of positive RAGE expression in the three groups of biopsies. Biopsies with dysplasia or in situ carcinoma had a significantly higher percentage of RAGE expression than the other groups of biopsies. CONCLUSIONS: The increased RAGE expression reported in both dysplasia and incipient cancer support the role of the multiligand/RAGE axis in gastric carcinogenesis.

Levels of CEA and Ca 19 - 9 in the sera and peritoneal cavity in patients with gastric and pancreatic cancers.

PURPOSE: Tumor markers are substances found in blood and other biological fluids if tumor is present in the body. They can be produced by tumor itself or can be results of cancer - body relation. They may be used in the follow-up of cancer patients to identify tumor recurrence. Pre-treatment levels have prognostic tool and could signalize persistence of minimal residual disease despite radical surgery. METHODS: We operated on 52 patients with upper GI malignancy (32 with gastric cancer and 20 with pancreatic cancer). Blood samples were taken before surgery and peritoneal samples immediately after laparotomy before any manipulation with tumor. All samples were examined by standard biochemical technique and the level was compared with a stage of the disease. RESULTS: Patients suffering from gastric carcinoma of stage I and II had higher level of both markers in sera then in the peritoneal cavity, however most of them were within physiological range. Patients in stage III and IV had average marker levels in the peritoneal cavity higher than in sera. Number of positive findings was increasing according to the stage of the disease. The peritoneal levels of both markers varied extremely in higher stages. In patients suffering from pancreatic carcinoma the CEA levels both in sera and peritoneal cavity were parallel but peritoneal levels were slightly higher in stages III and IV. Ca 19 - 9 was more sensitive for pancreatic cancer. The percentage of positive findings was higher in sera but the level of Ca 19 - 9 was higher in the peritoneal cavity. The number of positive findings again correlated with the stage of the disease. CONCLUSIONS: Levels of tumor markers in sera could signalize inoperability of tumor (Ca 19 - 9 in cases of pancreatic carcinoma); peritoneal levels could predict R1 resection especially in gastric cancer patients and risk of early peritoneal recurrence of the disease. Difference between the levels in the peritoneum and sera may signalize the route of dissemination (hematogenous and intraperitoneal).

Levels of CEA and Ca 19 - 9 in the sera and peritoneal cavity in patients with gastric and pancreatic cancers / Níveis de CEA e Ca 19 - 9 em soro e cavidade peritoneal em pacientes com câncer do estômago e pâncreas

PURPOSE: Tumor markers are substances found in blood and other biological fluids if tumor is present in the body. They can be produced by tumor itself or can be results of cancer - body relation. They may be used in the follow-up of cancer patients to identify tumor recurrence. Pre-treatment levels have prognostic tool and could signalize persistence of minimal residual disease despite radical surgery. METHODS: We operated on 52 patients with upper GI malignancy (32 with gastric cancer and 20 with pancreatic cancer). Blood samples were taken before surgery and peritoneal samples immediately after laparotomy before any manipulation with tumor. All samples were examined by standard biochemical technique and the level was compared with a stage of the disease. RESULTS: Patients suffering from gastric carcinoma of stage I and II had higher level of both markers in sera then in the peritoneal cavity, however most of them were within physiological range. Patients in stage III and IV had average marker levels in the peritoneal cavity higher than in sera. Number of positive findings was increasing according to the stage of the disease. The peritoneal levels of both markers varied extremely in higher stages. In patients suffering from pancreatic carcinoma the CEA levels both in sera and peritoneal cavity were parallel but peritoneal levels were slightly higher in stages III and IV. Ca 19 - 9 was more sensitive for pancreatic cancer. The percentage of positive findings was higher in sera but the level of Ca 19 - 9 was higher in the peritoneal cavity. The number of positive findings again correlated with the stage of the disease. CONCLUSIONS: Levels of tumor markers in sera could signalize inoperability of tumor (Ca 19 - 9 in cases of pancreatic carcinoma); peritoneal levels could predict R1 resection especially in gastric cancer patients and risk of early peritoneal recurrence of the disease. Difference between the levels in the peritoneum and sera may signalize the route of dissemination (hematogenous and intraperitoneal).

OBJETIVO: Os marcadores tumorais são substâncias encontradas no sangue e outros fluidos biológicos em pacientes com doenças oncológicas. São produzidos pelo próprio tumor ou ser resultado da interação entre o tumor e o organismo. Podem ser usados no seguimento de pacientes com câncer para identificar recidiva tumoral. Os níveis pré-tratamento têm valor prognóstico e podem sinalizar persistência de doença residual mínima após cirurgia radical.. MÉTODOS: Foram operados 52 pacientes com tumores do trato gastroinstestinal superior (32 com câncer do estômago e 20 do pâncreas). Amostras sanguineas foram colhidas no préoperatório e amostras peritoneais imediatamente após a laparotomia, antes de qualquer manipulação do tumor. Todas as amostras foram examinadas bioquímicamente e os resultados foram comparados entre si e em face ao progresso da doença. RESULTADOS: Os pacientes com câncer de estômago nos estadios I e II apresentaram níveis sanguineos mais elevados de ambos os marcadores tumorais do que no peritônio, mas a maioria dos valores encontrava-se dentro dos limites fisiológicos. Já nos estadios III e IV os níveis dos marcadores tumorais foram mais elevados no peritônio do que no sangue. O número de exames positivos aumentou de acordo com o estadio da doença. Nos estádios avançados, observou-se elevada variabilidade nos níveis de ambos os marcadores analisados no peritônio. Os doentes com carcinoma de pâncreas tiveram níveis de CEA semelhantes no sangue e no peritônio, mas os níveis peritoneais foram ligeiramente mais elevados nos estadios III e IV. Ca 19 - 9 foi muito mais sensível para o câncer do pâncreas. A porcentagem de exames positivos foi mais elevada no sangue, mas o níveis do Ca19-9 foram mais elevados no peritônio.A porcentagem de exames positivos também teve correlação com o estadio da doença. CONCLUSÕES: Os níveis de marcadores tumorais no sangue podem indicar inoperabilidade do tumor. No peritônio podem indicar o tipo de ressecção, especialmente nos doentes com câncer gástrico, e o risco de recidiva peritoneal precoce. A diferença entre os níveis no peritônio e sangue podem sinalizar a via de disseminação, hematogênica ou intra-peritoneal.

Identification of protein expression signatures in gastric carcinomas using clustering analysis.

BACKGROUND AND AIM: The identification of gastric carcinomas (GC) has traditionally been based on histomorphology. Recently, DNA microarrays have successfully been used to identify tumors through clustering of the expression profiles. Random forest clustering is widely used for tissue microarrays and other immunohistochemical data, because it handles highly-skewed tumor marker expressions well, and weighs the contribution of each marker according to its relatedness with other tumor markers. In the present study, we identified biologically- and clinically-meaningful groups of GC by hierarchical clustering analysis of immunohistochemical protein expression. METHODS: We selected 28 proteins (p16, p27, p21, cyclin D1, cyclin A, cyclin B1, pRb, p53, c-met, c-erbB-2, vascular endothelial growth factor, transforming growth factor [TGF]-ßI, TGF-ßII, MutS homolog-2, bcl-2, bax, bak, bcl-x, adenomatous polyposis coli, clathrin, E-cadherin, ß-catenin, mucin (MUC)1, MUC2, MUC5AC, MUC6, matrix metalloproteinase [MMP]-2, and MMP-9) to be investigated by immunohistochemistry in 482 GC. The analyses of the data were done using a random forest-clustering method. RESULTS: Proteins related to cell cycle, growth factor, cell motility, cell adhesion, apoptosis, and matrix remodeling were highly expressed in GC. We identified protein expressions associated with poor survival in diffuse-type GC. CONCLUSIONS: Based on the expression analysis of 28 proteins, we identified two groups of GC that could not be explained by any clinicopathological variables, and a subgroup of long-surviving diffuse-type GC patients with a distinct molecular profile. These results provide not only a new molecular basis for understanding the biological properties of GC, but also better prediction of survival than the classic pathological grouping.

[HER2 expression in gastric cancer in Peru]. / Expresión de HER2 en cancer gástrico en el Perú

HER2 positivity is thought to be a negative prognostic factor in gastric cancer (GC), correlating with poor survival rates. Reported HER2-positivity rates in GC have varied widely (6-35%). Objective of this study is to determine rate of positivity and describe clinical and pathological characteristics of HER-2(+) GC. 100 GC tumour samples were centrally screened by immunohistochemistry and FISH. 9% of cases were positive. More positivity HER2 was found in advanced stages (III/IV) vs. early stages (I/II)(p=0.045) ; intestinal histology subtype vs diffuse/ mixed (p=0.045) and gastro-oesophageal junction cancer vs GC ( p=0.005).

[Concomitant presence of a gastric adenocarcinoma and gastrointestinal stromal tumor: report of one case]. / Adenocarcinoma gástrico primario concomitante con tumor estromal gastrointestinal: reporte de un caso y revisión de literatura.

The concomitant presence of a primary gastric adenocarcinoma and a gastrointestinal stromal tumor in the stomach is uncommon. We report a 68-year-old male with an advanced gastric adenocarcinoma. During gastrectomy, a nodular intramural lesion was found. The pathological study, revealed a gastrointestinal stromal tumor, positive form CD117. After six months of follow up, there is no evidence of recurrence of either tumor).

Immunohistochemical expression of HER-2/NEU-CERBB-2 in patients with adenocarcinoma of the stomach / Expressão imunoistoquímica do HER-2/NEU-CERBB-2 em pacientes com adenocarcinoma do estômago

Objectives: To determine the prevalence of Her-2/Neu-cerbb-2 in the gastric mucosa of patients with gastric adenocarcinoma in a brazilian patient group. Methods: The immunohistochemical expression of Her-2/Neu was studied in 37 formalin-fixed paraffin–embedded tissue sections. Results: The immunohistochemical reaction produced by the anti-HER- 2/Neu antibody was positive in two cases (5.4%). Conclusion: The low prevalence of Her-2/Neu observed in these southern brazilian cases is probably due to the great number of poorly differentiated cancers in this serie.

Objetivo: Determinar a prevalência do Her-2/Neu-CerbB-2 na mucosa de pacientes com adenocarcinoma de estômago em um grupo de doentes brasileiros. Métodos: A expressão imunoistoquímica do Her-2/Neu foi estudada em 37 amostras de tecidosfixados em formalina e embebidos em parafina. Resultados: A reação imunoistoquímica produzida pelo anticorpo HER-2/Neu foi positiva em dois pacientes (5.4%). Conclusão: A baixa prevalência Her-2/Neu observada neste grupo de pacientes é provavelmente devida ao grande número de tumores pouco diferenciados encontrados nesta série.

Adenocarcinoma gástrico primario concomitante con tumor estromal gastrointestinal: Reporte de un caso y revisión de literatura / Concomitant presence of a gastric adenocarcinoma and gastrointestinal stromal tumor: Report of one case

The concomitant presence of a primary gastric adenocarcinoma and a gastrointestinal stromal tumor in the stomach is uncommon. We report a 68-year-old male with an advanced gastric adenocarcinoma. During gastrectomy, a nodular intramural lesion was found. The pathological study, revealed a gastrointestinal stromal tumor, positive form CD117. After six months of follow up, there is no evidence of recurrence of either tumor.