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.

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.

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.

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.

An Inverse Relationship between the Expression of the Gastric Tumor Suppressor RUNX3 and Infection with Helicobacter pylori in Gastric Epithelial Dysplasia

BACKGROUND/AIMS: This study was performed to determine the association between RUNX3 expression and Helicobacter pylori infection in premalignant gastric lesions. METHODS: We examined 107 patients with gastric epithelial dysplasia who had undergone endoscopic mucosal resection or submucosal dissection. All tissue samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H. pylori infection in dysplastic lesions and the normal surrounding tissue was examined by silver staining, and cagA status was assessed by polymerase chain reaction. RESULTS: The loss of RUNX3 expression was observed in 62 cases (57.9%), and an association with H. pylori infection was found in 54 cases (50.5%). The infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3-negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of category 4 lesions (according to the revised Vienna classification) were high (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3-negative category 4 lesions, the rate of cagA-positive H. pylori infection rate was high but not significantly increased (p=0.08). CONCLUSIONS: Infection with H. pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis. This mechanism was prominent in gastric cancer with a gastric mucin phenotype.

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.

A Tulip-Shaped Gastric Carcinoid Tumor

No abstract available.

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.

Levels of carcinoembryonic antigen and CA 19-9 in the sera and peritoneal washing of patients undergoing surgical treatment for gastric carcinoma / Níveis do antígeno carcinoembriônico e do CA 19-9 no soro e no lavado peritonial em doentes submetidos ao tratamento cirúrgico do carcinoma gástrico

BACKGROUND: Early peritoneal recurrence of gastric carcinoma following curative resection remains a great challenge in the treatment and prevention of this disease. AIM: To analyze the relationship between levels of tumor markers, carcinoembryonic antigen (CEA) and CA 19-9 in the sera and peritoneal washing, and anatomopathological aspects of the gastric carcinoma. METHODS: Of the 46 patients in the study, 29 (63.0 percent) were males and 17 (37.0 percent) females. Mean age was 63.6 ± 11.7 years (31 to 91 years). Peripheral venous blood samples were collected from the upper limb vein from both patient groups after anesthetic induction, in order to determine serum levels of CEA and CA 19-9. After the end of the procedure, 50 mL of physiologic solution was introduced into the bottom of the Douglas sack and a portion aspirated to determine CEA and CA 19-9 levels in the peritoneal washing. Levels of CEA and CA 19-9 in the sera and peritoneal washing were compared to the following variables: lesion diameter ≤4 cm or >4 cm, lymph node involvement, angiolymphatic invasion, depth of invasion into gastric wall, and initial or late stage. RESULTS: Sera CEA levels were significantly higher in patients with lesions >5 cm. CEA levels in the sera and peritoneal washing were significantly greater in patients with signet ring cell gastric carcinoma. In addition, levels of CEA in peripheral blood and peritoneal washing showed significant association with the degree of carcinoma penetration into the gastric wall, while sera CEA was significantly higher in patients at more advanced stages. There was no significant difference between sera and peritoneal CEA values regarding grade of differentiation. Patients with gastric lesions measuring > 5cm and more differentiated lesions had significantly higher sera CA 19-9 values. In patients with lymph nodes invasion by gastric carcinoma, CA 19-9 levels in peritoneal washing were significantly higher than in ...

RACIONAL: A recidiva peritonial precoce do carcinoma gástrico operado com intenção curativa continua sendo um grande desafio do seu tratamento e prevenção. OBJETIVO: Analisar a relação entre os níveis do marcador tumoral antígeno carcinoembriônico (CEA) e CA 19-9 no sangue e no lavado peritonial e os aspectos anatomopatológicos do carcinoma gástrico. MÉTODO: Dos 46 doentes do estudo, 29 (63,0 por cento) eram do sexo masculino e 17 (37,0 por cento) do feminino. A média de idade foi de 63,6 ± 11,7 anos (31 a 91 anos). Após a indução anestésica, o sangue venoso periférico foi coletado de veia do membro superior para a determinação do nível sérico do CEA e CA 19-9. Após o término do procedimento operatório foram derramados 50 mL de solução fisiológica no fundo de saco de Douglas, aspirada alíquota que foi encaminhada para a determinação do nível no lavado peritonial do CEA e CA 19-9. O nível do CEA e do CA 19-9 sérico e no lavado peritonial foram relacionados às seguintes variáveis: diâmetro da lesão ≤4 cm ou >4 cm, comprometimento linfonodal, invasão angiolifática, profundidade de invasão na parede gástrica e estádio inicial ou tardio. RESULTADOS: Em relação ao CEA, o nível sérico foi significantemente maior nos doentes com o diâmetro da lesão >5 cm. O nível de CEA sérico e no lavado peritonial foi significantemente maior nos doentes com carcinoma gástrico com células em anel de sinete. O nível de CEA no sangue periférico e no lavado peritonial mostrou relação significante com o nível de penetração do carcinoma na parede gástrica, e o CEA sérico foi significantemente mais elevado nos doentes com estádio mais avançados. Não houve diferença significante entre os valores do CEA sérico e peritonial nos carcinomas mais diferenciados em relação aos menos diferenciados. No tocante ao CA 19-9, os enfermos com lesões gástricas com diâmetro >5 cm e mais diferenciadas exibiram valores séricos de CA 19-9 significantemente maiores. Nos doentes ...

Expression of Cyclooxygenase-2, p53 and Ki-67 in Gastric Cancer

It has been reported that p53 mutation may contribute to upregulate cyclooxygenase (COX)-2 expression that is observed in malignant tissues. These molecules are involved in carcinogenesis by affecting tumor cell proliferation. The aim of this study was to examine the relationship between COX-2 or p53 expression and clinico-pathological characteristics including tumor cell proliferation in gastric cancer. COX-2 and p53 expressions were investigated with immunostaining, in tissue specimens obtained from 119 patients who underwent surgery for gastric cancer. The Ki-67 labeling index (LI) was counted by Ki-67 immunostaining. COX-2 and p53 expressions correlated significantly with depth of tumor invasion. However, there was no association between COX-2 or p53 expression and survival. p53 expression did not correlate with COX-2 expression. There was no significant difference in various clinicopathological variables between Ki-67 LI subgroups. The mean Ki-67 LI value of COX-2 positive tumors was significantly higher than that of negative tumors. The mean Ki-67 LI value of p53 positive tumors was not significantly higher than that of negative tumors. The mean Ki-67 LI value of both COX-2 and p53 positive tumors was significantly higher than that of both negative tumors. These results imply that COX-2 expression is associated with tumor cell proliferation of gastric cancer.

Clinicopathological Features and Differences of p53 and Ki-67 Expression in Adenosquamous and Squamous Cell Carcinomas of the Stomach / 대한소화기학회지

BACKGROUND/AIMS: This study reviewes the clinicopathological features, prognosis, and differences in the expression of p53 and Ki-67 immunochemical staining in squamous cell and adenosquamous carcinoma of the stomach. METHODS: From January 1995 to June 2005, 2,282 cases of gastric carcinoma were resected surgically in our hospital and 191 additional cases were resected by endoscopic mucosal resection. Retrospective pathologic review and immunochemical staining of p53 and Ki-67 were performed. RESULTS: The study consists of eight cases (0.032%) of primary squamous cell carcinoma (one case) and adenosquamous carcinoma (seven cases) without early gastric cancer. Six cases (75.0%) were male and two cases were female. The mean age was 66 year-old. The clinical presentation and physical findings did not differ from those of adenocarcinoma. The mean tumor size was 5.2+/-1.7 cm. Macroscopically, five were Borrmann type 3 (62.5%) and three were type 2. At the initial diagnosis, six (75%) were stage IV based on TNM tumor staging. Six cases (75%) progressed despite the therapy while two cases responded to the treatment. The median survival time was 11.0 months (range 4.3+/-17.7). Overexpression of p53 was seen in five cases (62.5%) and their survival was poor when compared to the p53-negative group (p=0.04). The mean Ki-67 labeling index was 70.0+/-20.8%, and was not associated with p53 staining (p>0.05). CONCLUSIONS: Adenosquamous and squamous cell carcinoma of the stomach are very rare. They tend to be at advanced stages on initial diagnosis, and progress rapidly. They show p53 protein overexpression and high Ki-67 labeling index, which might be related to poor prognosis.

Expression of CD40 in Gastric Cancer and Its Effect on the Apoptosis of Gastric Cancer Cells / 대한소화기학회지

BACKGROUND/AIMS: The expression of CD40 in gastric cancer has not been studied. The aims of this study were to determine the expression of CD40 in gastric cancer and to investigate the effect of CD40 on the apoptosis of gastric cancer cells. METHODS: We examined the expression of CD40 by immunohistochemistry and flow cytometry. CD40 mRNA in 5 gastric cancer cell lines was analyzed by RT-PCR. To assess the effect of CD40 on the viability of gastric cancer cells, we performed MTT assay. The effect of CD40 signaling on the apoptosis of gastric cancer cells was examined by annexin V affinity assay. RESULTS: Twelve of twenty human gastric cancer tissues demonstrated positive staining for CD40. Among 5 gastric cancer cell lines, AGS cell line expressed membrane-bound CD40 antigen and CD40 mRNA. In AGS cells, CD40 stimulation significantly reduced the cell viability. CD40 ligation significantly increased the apoptosis in AGS cells compared to the control. CONCLUSIONS: CD40 is expressed in human gastric cancer tissues and gastric cancer cell line, and induces apoptosis in gastric cancer cells. These results suggest that CD40 expression in gastric cancer may play an important role in host defense mechanism against the gastric cancer.

Expressions of p53 and p21 in Primary Gastric Lymphomas

The p21 overexpression is thought to be a consequence of the p53 induced activation of the p21 gene. The immunohistochemical evaluation of p53 and p21 can be a valuable means of assessing the functional status of the p53 gene product. We examined the overexpression of p21 and p53 proteins in primary gastric lymphomas and the correlation with prognosis. A total of 32 cases of gastric lymphomas was classified into low-grade lymphomas of mucosa-associated lymphoid tissue type (n=16) and high-grade B-cell lymphomas (n=16). In low-grade lymphomas, only one case showed p53 positivity and all cases were p21-negative. In high-grade lymphomas, seven cases were p53+/p21- (44%), one case was p53+/p21+ (6%), and eight cases were p53-/p21- (50%). The p53+/p21- cases had a much lower percentage of patients sustaining a continuous complete remission state (3/7, 43%) compared with other cases (6/7, 86%). From these results, we concluded that p21 expression is rare in primary gastric lymphomas. Therefore, p53-positive lymphomas can be assumed as having p53 mutation. And combined studies of p53 and p21 may be used as a prognostic indicator in primary gastric high-grade lymphomas.

DNA ploidy patterns in gastric adenocarcinoma

To assess the value of DNA ploidy, flow cytometric analysis was performed on unfixed fresh materials obtained from 86 patients with gastric cancer who underwent stomach resection. We evaluated the DNA content of gastric carcinoma cells from four different sites and compared it with Ki-67 proliferating activity, and other pathologic parameters. The incidence of aneuploid and diploid was similar (48.8% vs. 51.1%). Early gastric carcinoma showed a higher rate of the diploid pattern (75%) compared to that of advanced gastric carcinoma 7.3%). DNA diploidy was noted increasingly in diffuse-type tumors according to uren, in signet ring cell type tumor according to WHO classification and in orly differentiated tumors (p<0.05). Well and moderately differentiated rcinomas revealed the aneuploid pattern more frequently than poorly fferentiated tumors. The aneuploidy was associated with high S phase fraction d high proliferative index. Aneuploidy was noted in the mucosa adjacent to the mor (26%), in the close normal-looking mucosa (7%) and in the remote rmal-looking mucosa (3%). This result suggest the possible role of field ncerization in the development of gastric adenocarcinoma.

c-Myc expression is related with cell proliferation and associated with poor clinical outcome in human gastric cancer

We underwent protein assay for Myc expression in 76 human gastric cancer tissues using immunohistochemistry. Expression of Myc protein was analyzed according to proliferative indices measured by flow cytometry. Levels of Myc protein expression was evaluated by correlating with biologic and clinical parameters. In 36 (47.4%) of 76 primary gastric cancers, overexpression of Myc was observed. We could observe expression of Myc protein in a significant portion of early gastric cancer (42.9%). Expression of Myc protein was demonstrated to be more frequent in poorly differentiated cancer cells (p=0.043). However, expression of Myc protein had little influence over progress or extent of the disease. Expression of Myc protein was significantly correlated with increased proliferative activity (p=0.032) and patients with high levels of Myc expression had poor disease-free survival. In a certain proportion of human gastric cancer, Myc protein may function as a regulator of cancer cell growth and expression of Myc may represent an aggressive phenotype of gastric cancer.

Expression of p53 and NDP-K/nm23 in gastric carcinomas: association with metastasis and clinicopathologic parameters

To evaluate the role of p53 and NDP-K/nm23(nm23) protein as a prognostic factor and their relation to metastasis of cancer, we studied metastatic and nonmetastatic gastric carcinoma specimens by immunohistochemical staining. Among the 101 specimens examined, 37(36.6%) showed positivity in staining for p53 protein and 64(63.4%) showed no detectable p53 protein in tumor cells. p53 overexpression was correlated with depth of invasion, lymphatic invasion, lymph node metastasis and distant metastasis. Out of 101 specimens, 35 cases had no staining for nm23. 62 cases(61.4%) exhibited a cytoplasmic staining on most cells and 42 cases (41.6%) had nuclear staining. In 16 of 101 cases(15.8%), a mild to moderate membranous staining was observed in some cells. Cytoplasmic nm23 expression was negatively correlated with lymph node metastasis(P < 0.01) and distant metastasis(P < 0.01). The nuclear nm23 expression showed negative correlation with depth of invasion(P < 0.01), lymphatic invasion(P < 0.01), lymph node metastasis(P < 0.01), and distant metastasis(P < 0.04). The membranous nm23 expression revealed negative correlation with lymphatic invasion(P < 0.02), lymph node metastasis(P < 0.01) and distant metastasis(P < 0.02).

The prognostic significance of c-erbB-2 and p53 protein expressions in gastric carcinoma: a multivariate analysis of prognostic factors

152 curative gastrectomy specimens from patients with gastric carcinoma were examined in an attempt to assess the prognostic value of c-erbB-2 and mutant p53 protein expressions. The labeled streptavidin-biotin method was applied to routinely fixed and paraffin-embedded tissue sections, using the polyclonal and monoclonal antibodies against the c-erbB-2 protein and the mutant form p53 protein, respectively. In this examination, staining of c-erbB-2 protein was found in 9.2% of these carcinomas. The c-erbB-2 stained tumors were significantly associated with the tumors whose diameters were smaller than 5cm, and were more likely to be associated with serosal invasion and nodal involvement than the unstained ones. However, there was little association between staining of c-erbB-2 protein and clinicopathologic findings such as age, sex, location, histology, gross type, lymph node status, depth of invasion, and stage. The survival analysis of 104 patients with stage III gastric carcinoma revealed no significant association between c-erbB-2 staining status and survival duration. The 5-year survival rates of the c-erbB-2 positive group and its negative group were 21% and 28%, respectively. Positive p53 protein expression was observed in 46% of 152 carcinomas. There was no significant association between p53 expression and parameters such as age, sex, location, histology, gross type, and size. The p53 stained tumors were more likely to be associated with lymph node metastasis, serosal invasion than p53 unstained ones; but this did not reach significance. The 5-year survival rates of the p53 positive group and counter part group were 27% and 31%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemical detection of p53 protein, c-erbB-2 protein, epidermal growth factor receptor protein and proliferating cell nuclear antigen in gastric carcinoma

There is increasing evidence that genes involved in normal cell growth and differentiation (oncogenes) or genes that encode for growth factors are important in determining the development and biologic aggressiveness of gastric carcinoma. This study was undertaken to define the prognostic value of the overexpression of p53 protein, c-erbB-2 protein, EGFr protein and PCNA in gastric carcinomas. Using monoclonal antibodies, immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections from 84 primary gastric carcinomas. Overall, 34% of gastric carcinomas had nuclear-staining for p53 protein, 34% of carcinomas membrane staining for the c-erbB-2 and 74% of carcinomas membrane and cytoplasmic staining for EGFr, showing distribution in a heterogeneous fashion. PCNA was expressed as Grade 2 and 3 in 75% of patients with gastric carcinomas. Both c-erbB-2 and p53 staining was significantly associated with high grade expression of PCNA. p53 staining tended to be associated with positive nodal status and metastasis, and c-erbB-2 staining with positive nodal status only. Multivariate analysis using the Cox model showed that overexpression of p53 protein, c-erbB-2 protein and PCNA was not an independent prognostic variable in gastric carcinoma. These results suggest that expressions of p53 and c-erbB-2 protein are heterogeneous and that p53 and c-erbB-2 overexpressions are significantly associated with high proliferative activity in gastric carcinoma.