Comparative immunohistochemical study of MUC1 and carbohydrate antigens in breast benign disease and normal mammary gland.

The aim was to compare the expression of MUC1 and carbohydrate antigens in 124 tissue samples; 42 fibroadenoma (FA), 23 nonproliferative benign diseases (NPF), 25 usual epithelial hyperplasia (UEH), 7 atypical ductal hyperplasia (ADH), and 27 breast normal tissues. An immunohistochemical approach was adopted, using the following antibodies: reactive with MUC1 variable number of tandem repeats (C595, HMFG2, and SM3 monoclonal antibodies), anti-MUC1-cytoplasmic tail polyclonal antibody (CT33), and anti-carbohydrate antigens (sialyl Lewis x, Lewis x, Lewis y, Tn, and Thomsen-Friedenreich epitopes). Positive area of reaction, intensity, and pattern of expression were considered. A reactivity index was calculated as intensity (I) x 100+percentage of positive area (A). Statistical analysis comprised frequency analysis, P < 0.05, analysis of variance, and multiple correlation with principal component analysis. All samples expressed MUC1, detected by at least one anti-MUC1 antibody whereas Lewis x was the carbohydrate antigen most frequently found in all groups whereas variable number of tandem repeats MUC1 and Lewis x showed the highest correlation: 93% of normal samples, 62.5% of NPF, 87% of FA, 85% of UEH, and finally 80% of ADH. Although principal component analysis using reactivity indexes explained only 39% of data variability, normal samples appeared grouped and separated from benign breast diseases, which remained spread. Thomsen-Friedenreich was the only antigen that showed an increased tendency for positive expression and intensity from NPF through FA, UEH to ADH, whereas it was not detected in normals. With respect to the pattern of expression, an apical pattern was predominantly found in all the groups.

Omeprazole-associated changes in the gastric mucosa of children.

AIMS: To describe histological findings in gastric mucosa biopsy specimens of children treated with proton-pump inhibitors (PPIs) for different periods of time. METHODS: Biopsy specimens from 12 children (aged 8 months to 15 years) treated with PPIs and 8 controls were processed for paraffin embedding and stained with H&E as well as inmmunohistochemically for sialyl-Tn antigen. RESULTS: The main changes were related to parietal cells which showed brisk cytoplasmic eosinophilia, apical cytoplasmic protrusions to dilated glands, cytoplasmic and nuclear hypertrophy, dilated intracytoplasmic canaliculi, binucleation and multinucleation. The intracellular canaliculi surface showed strong immunohistochemical reaction for sialyl-Tn antigen, apparently a marker for this structure. Some of the patients were biopsied after a short period of oral or intravenously administered omeprazole; the changes may therefore occur rapidly. CONCLUSIONS: PPIs induce the same changes in the gastric mucosa of children as in adults, but the number of nuclei is increased. These effects have not been reported previously in this age group. It is suggested that the changes result from a combination of effects of PPIs and gastrin release.

CA72-4 antigen levels in serum and peritoneal washing in gastric cancer. Correlation with morphological aspects of neoplasia.

BACKGROUND: Determining levels of tumor markers in peritoneal washing enables likelihood of peritoneal recurrence to be ascertained in patients with high marker levels, thereby allowing provision of more accurate adjuvant treatment and postoperative follow up. AIM: To analyze the relationship between levels of tumor marker CA72-4 in serum and peritoneal washing, and morphological aspects of gastric carcinoma. METHOD: This study analyzed 32 consecutively-operated patients with gastric carcinoma, who underwent subtotal, total or palliative gastrectomy. The variables studied were CA72-4 levels in serum and peritoneal washing, lesion site, stage, degree of cell differentiation, operation performed, and number of extirpated and involvement lymph nodes. Of the 32 patient sample, 21 (65.6%) were male and 11 (34.4%) female. Mean age was 62.6 +/- 14.2 years (29 to 91 years). Following anesthetic induction, peripherical venous blood was collected through percutaneous punction of an upper limb vein. After the procedure, 50 mL of physiologic solution at 37 degrees C was introduced into the cul-de-sac. A 10 mL volume of this liquid was aspirated from the cavity and the peritoneal washing tested for CA72-4 levels. Normal values for CA72-4 levels in serum were considered < or =7 U/mL and high levels as >7 U/mL, whilst for the peritoneal washing normal levels were < or =0.61 U/mL, and abnormal >0.61 U/mL. RESULTS: Mean pre-operative serum levels for CA72-4 were 6.55 U/mL +/- 15.30 (0.3 to 75.30 U/mL) whilst the mean level of CA72-4 in peritoneal washing was 8.50 U/mL +/- 26.72 (0.3 to 142.00 U/mL); correlation between these levels was significant. Lymph nodes involvement by the gastric carcinoma correlated significantly with higher CA72-4 levels in both serum and peritoneal wash. There was no statistically significant correlation between serum level of CA72-4 and invasion into serosa by the gastric carcinoma. There was however, significant correlation between peritoneal washing levels of CA72-4 and involvement of serosa by gastric carcinoma. There was also a significant correlation between more advanced stages of gastric carcinoma and higher levels of CA72-4 in the peritoneal washing, although serum levels of CA72-4 and more advanced stage of gastric neoplasia showed no significant correlation. Degrees of cellular differentiation in the gastric carcinoma did not differ significantly with CA72-4 levels in serum or peritoneal washing. CONCLUSION: High levels of CA72-4 in peritoneal washing correlated significantly with lymph node metastasis and serosa involvement by the neoplasia, and also with more advanced stage of gastric carcinoma. The levels of CA72-4 in the blood correlated significantly with lymph node involvement by the gastric carcinoma, but not with serosa invasion or more advanced stage of neoplasia.

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

OBJECTIVE: 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% of the cases and the Tn was positive in 48%. In the columnar cells, Stn was always negative, while Tn was positive in 100% of the cases. However, in adenocarcinoma in BE, both antigens were 100% 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.

CA72-4 antigen levels in serum and peritoneal washing in gastric cancer: correlation with morphological aspects of neoplasia

BACKGROUND: Determining levels of tumor markers in peritoneal washing enables likelihood of peritoneal recurrence to be ascertained in patients with high marker levels, thereby allowing provision of more accurate adjuvant treatment and postoperative follow up. AIM: To analyze the relationship between levels of tumor marker CA72-4 in serum and peritoneal washing, and morphological aspects of gastric carcinoma. METHOD: This study analyzed 32 consecutively-operated patients with gastric carcinoma, who underwent subtotal, total or palliative gastrectomy. The variables studied were CA72-4 levels in serum and peritoneal washing, lesion site, stage, degree of cell differentiation, operation performed, and number of extirpated and involvement lymph nodes. Of the 32 patient sample, 21 (65.6 percent) were male and 11 (34.4 percent) female. Mean age was 62.6 ± 14.2 years (29 to 91 years). Following anesthetic induction, peripherical venous blood was collected through percutaneous punction of an upper limb vein. After the procedure, 50 mL of physiologic solution at 37ºC was introduced into the cul-de-sac. A 10 mL volume of this liquid was aspirated from the cavity and the peritoneal washing tested for CA72-4 levels. Normal values for CA72-4 levels in serum were considered <7 U/mL and high levels as >7U/mL, whilst for the peritoneal washing normal levels were <0.61 U/mL, and abnormal >0.61 U/mL. RESULTS: Mean pre-operative serum levels for CA72-4 were 6.55 U/mL ± 15.30 (0.3 to 75.30 U/mL) whilst the mean level of CA72-4 in peritoneal washing was 8.50 U/mL ± 26.72 (0.3 to 142.00 U/mL); correlation between these levels was significant. Lymph nodes involvement by the gastric carcinoma correlated significantly with higher CA72-4 levels in both serum and peritoneal wash. There was no statistically significant correlation between serum level of CA72-4 and invasion into serosa by the gastric carcinoma. There was however, significant...

RACIONAL: A determinação dos níveis de marcadores tumorais no lavado peritonial apresenta a possibilidade de indicar tendência à recidiva peritonial nos doentes com níveis elevados, o que pode indicar tratamento adjuvante e seguimento pós-operatório mais acurado. OBJETIVO: Analisar a relação entre os níveis do marcador tumoral CA72-4 no sangue e no lavado peritonial e os aspectos morfológicos do carcinoma gástrico. MÉTODO: Foram analisados 32 doentes operados consecutivamente, com carcinoma gástrico e submetidos a gastrectomia subtotal, total ou paliativa. Foram estudadas as seguintes variáveis: nível sérico e no lavado peritonial do CA72-4, localização da lesão, estádio, grau de diferenciação celular, operação realizada, e número de linfonodos extirpados e acometidos. Dos 32 doentes do estudo, 21 (65,6 por cento) eram homens e 11 (34,4 por cento) mulheres. A média de idade foi de 62,6 ± 14,2 anos (29 a 91 anos). Logo após a indução anestésica, o sangue venoso periférico foi coletado por punção percutânea de veia do membro superior. Após o término da operação, 50 mL de solução fisiológica aquecida a 37ºC foi derramado no fundo de saco. Desse líquido, foi aspirado o volume de 10 mL e encaminhado para a determinação do nível do CA72-4 no lavado peritonial. Para o nível sérico do CA72-4 foram considerados normais os valores < a 7 U/mL e elevados os valores > que 7 U/mL. Para o nível no lavado peritonial do CA72-4 foram considerados normais os valores < 0,61 U/mL, e alterados os valores > que 0,61 U/mL. RESULTADOS: média do nível sérico do CA72-4 no pré-operatório foi de 6,55 U/mL ± 15,30 (0,3 a 75,30 U/mL) e a média do nível do CA72-4 no lavado peritonial foi de 8,60 U/mL ± 26,72 (0,3 a 142,00 U/mL); a correlação entre esses níveis foi significativa. O acometimento linfonodal pelo carcinoma gástrico correlacionou-se significantemente com os níveis mais elevados do CA72-4 sérico e peritonial. Não houve diferença significativa...

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.

Characterization of the carcinoma-associated Tk antigen in helminth parasites.

Expression of Tk antigen, a truncated carbohydrate antigen, was examined in helmith parasites. Using the monoclonal antibody LM389, this antigen was detected in extracts from Taenia hydatigena, Mesocestoides vogae (syn corti), and Taenia crassiceps. No reactivity was observed in Thysanosoma spp., Dipylidium caninum, Fasciola hepatica, and Nyppostrongylus brasiliensis. On the basis of their electrophoretic mobility, different patterns of Tk-bearing glycoproteins were observed among T. hydatigena, M. corti and T. crassiceps by immunoblotting, with certain components resolved as broad bands typical of mucin-like glycoproteins. Most Tk-reactive material remained in the 0.6 N perchloric acid-soluble fraction, confirming that Tk epitopes are carried by mucin-type glycoproteins. Immunohistochemical analysis revealed that in T. hydatigena, Tk antigen is mainly expressed in the tegument, whereas in M. corti the reactivity was principally observed in the subtegumental parenchyma. The presence of a novel tumor-associated carbohydrate antigen in invertebrates, contributes to strengthen the notion that truncated mucin-type O-glycosylation is a normal phenomenon in parasitic worms and may help identify new biological characteristics of helminth parasites.

Simple mucin-type cancer associated antigens are pre-cancerous biomarkers during 1,2-dimethylhydrazine-induced rat colon carcinogenesis.

The simple mucin-type truncated O-glycans Tn (GalNAc-O-Ser/Thr) and sialyl-Tn (STn) antigens are useful diagnostic markers for human colon cancer. We herein report the characterization of 1,2-dimethylhidrazine (DMH)-induced colon cancer in rats as a new model for the study of aberrant O-glycosylation products during carcinogenesis. Evaluated by immunohistochemistry, both anti-Tn and anti-STn MAbs revealed no staining of normal colonic mucosa. On the contrary, Tn and STn were expressed by the first lesions detected following carcinogen administration (aberrant crypt foci), observing the most intense and uniform pattern in crypts with severe dysplasia. Adenocarcinomas with non-secreting components showed moderately and strong stain, but mucin-secreting carcinomas were mildly stained. The biochemical characterization of soluble Tn glycoproteins from ascitic fluids of rats with colon cancer revealed that Tn is bearing high molecular weight glycoproteins (containing sialic acid and/or GlcNAc and GalNAc), which migrated as two major components (one of approximately 220 kDa and other>500 kDa). Evaluated by CsCl gradient ultracentrifugation and perchloric acid precipitation, it was shown that Tn is carried for mucins. These results indicate that Tn and STn are pre-cancerous biomarkers in colon of rats treated with DMH. This model of rat colon cancer could be useful to study in vivo the temporal sequence of molecular events responsible for the deregulation of O-glycosylation pathways during colon carcinogenesis, and could contribute to improve the evaluation of diagnostic and therapeutic strategies based on the utilization of Tn and STn antigens.

[Typing of colorectal epithelium by lectin histochemistry: expression of T glycoepitope]. / Tipificación del epitelio colorrectal por lectinhistoquímica: expresión del glicotope T.

The current study deals with the setting up of a new tool that enables the benign versus the malignant nature of colorectal epithelium to be determined early and accurately. The objective is to determine a different biologic characteristic between normal and malignant colorectal tissue, which is the site and the level of expression of the T glycoepitope (Thomsen-Friedenreich antigen). It was characterized in a series of 62 colorectal samples, including 31 normal (without pathologic lesion) and 31 cancerous (mostly moderately or poorly differentiated) tissue sections. The glycoconjugate expression was demonstrated by lectin-histochemistry, using PNA lectin. The binding patterns of the lectin were determined in both columnar and goblet cells, from normal and malignant colorectal tissue. The results show that specific and different glycochemical staining patterns could be identified between benign and malignant epithelium. The data of the cytostructural localization were submitted to statistical analyses, which strongly suggested the association between the patterns of expression of the T antigen and the degree of the tissue differentiation. The methodology developed can be applied directly in routine diagnosis and it has an important prognostic value.

Tipificación del epitelio colorrectal por lectinhistoquímica: expresión del glicotope T / Typing of colorectal epithelium by lectin histochemistry if the T glycoepitope

El presente estudio refiere a una nueva herramienta que permite detectar fechaciente y tempranamente la naturaleza maligna del epitelio colorrectal. El objetivo es determinar una característica biológica diferente entre tejido normal y neo-plásico, como es el nivel de expresión del glicoepitope T (Ag Thomsen-Friedenreich). Se lo caracterizó en una serie de 62 muestras del tejido en estudio, incluyendo 31 normales (sin lesiones anatomopatológicas) y 31 correspondientes a cánceres (en su mayoría moderada o pobremente diferenciados). La expresíon del glicoconjugado se demostró por tectínhistoquímica, usando lectina PNA. Los patrones de unión de lectina fueron determinados en células absortivas (cilídricas) y caliciformes, normales y neoplásicas, encontrándose patrones característicos y diferentes según tipo de célula y naturaleza del tejido. El análisis estadístico de la localización citoestructural del Ag T en ambas poblaciones sugiere fuertemente que existe asociación entre el patrón de expresión y el grado de diferenciación tisular. La sencillez de la metodología hace a la determinación aplicable en diagnóstico de rutina y además tiene importante valor pronóstico.

Tipificación del epitelio colorrectal por lectinhistoquímica: expresión del glicotope T / Typing of colorectal epithelium by lectin histochemistry if the T glycoepitope

El presente estudio refiere a una nueva herramienta que permite detectar fechaciente y tempranamente la naturaleza maligna del epitelio colorrectal. El objetivo es determinar una característica biológica diferente entre tejido normal y neo-plásico, como es el nivel de expresión del glicoepitope T (Ag Thomsen-Friedenreich). Se lo caracterizó en una serie de 62 muestras del tejido en estudio, incluyendo 31 normales (sin lesiones anatomopatológicas) y 31 correspondientes a cánceres (en su mayoría moderada o pobremente diferenciados). La expresíon del glicoconjugado se demostró por tectínhistoquímica, usando lectina PNA. Los patrones de unión de lectina fueron determinados en células absortivas (cilídricas) y caliciformes, normales y neoplásicas, encontrándose patrones característicos y diferentes según tipo de célula y naturaleza del tejido. El análisis estadístico de la localización citoestructural del Ag T en ambas poblaciones sugiere fuertemente que existe asociación entre el patrón de expresión y el grado de diferenciación tisular. La sencillez de la metodología hace a la determinación aplicable en diagnóstico de rutina y además tiene importante valor pronóstico. (AU)

Detection and isolation of MUC1 mucin from larynx squamous cell carcinoma.

UNLABELLED: The progression from uncontrolled cell proliferation to invasion and metastasis of epithelial tumors is partially understood. Alteration of epithelial mucin expression have been described in different malignant localizations but only few attempts have been made to identify mucin expression in malignant laryngeal tumors. In the present report, results are shown of studies on the expression of mucins and carbohydrate related antigens in laryngeal cancer and on the isolation of MUC1 mucin from this tumor tissue. Malignant laryngeal specimens were processed for immunohistochemical analysis and for extranuclear membrane fractions (ENM) which were obtained by ultracentrifugation. Subsequently, ENM samples were centrifuged in density-gradient; the analysis of fractions was performed by means of SDS-PAGE and Western-blotting. The panel of monoclonal antibodies (MAbs) included anti MUC1 mucin, anti Lewis x, anti sialyl Lewis x, anti Lewis y, anti MUC-5B, anti oral mucin (gp230), anti Tn hapten, anti p53 and anti cytokeratins. By immunohistochemistry, it was possible to detect MUC1 mucin, Lewis x and Lewis y showing strong reactions while sialyl-Lewis x and Tn antigen only reacted weakly in a few cells; cytokeratins were detected in all samples. In ENM derived fractions obtained by CsCl centrifugation, MUC1 was demonstrated by Western blotting. CONCLUSIONS: (1) laryngeal cancer antigenic expression comprises mostly MUC1 mucin, Lewis x, Lewis y as well as Tn antigen and (2) the methodology here employed is useful to isolate MUC1 from tumor samples.

Tn antigen is a pre-cancerous biomarker in breast tissue and serum in n-nitrosomethylurea-induced rat mammary carcinogenesis.

The Tn determinant (GalNAcalpha-O-Ser/Thr), normally a cryptic structure in mucin-type O-glycans, is a tumor-associated marker which has attracted particular interest in cancer biology. We herein report the characterization of N-nitrosomethylurea (NMU)-induced breast cancer in rats as a new model for the study of aberrant O-glycosylation products. Tn-antigen expression is detectable not only in mammary carcinoma induced by NMU but also in carcinogen-initiated mammary epithelium, indicating that Tn could be a pre-cancerous biomarker in rats treated with NMU. Serum Tn levels were followed up longitudinally in 30 rats from the time of the first injection of NMU to the development of advanced breast cancer. Tn antigen increased in serum several weeks before tumor development, and became highly positive after 56 days of carcinogenesis (prior to breast-cancer occurrence), and the levels correlated with Tn expression in mammary tissues. However, during the follow-up after detection of mammary cancer, all animals displayed a significant decrease of serum Tn antigen, and low levels were observed in animals with advanced breast cancer. We have shown that the humoral immune response to cancer, with the production of anti-Tn antibodies, could hamper the detection of Tn antigen in animals with advanced breast cancer. These results suggest that NMU-induced rat mammary carcinogenesis is a useful experimental model to study the regulation of O-glycosylation at the cellular level during malignant transformation.

Sialosyl-Tn antigen as a marker of gastric cancer progression: an international study.

Sialosyl-Tn, a mucin-associated carbohydrate antigen, is not expressed by normal mucus-producing cells of the stomach but becomes expressed in metaplastic, pre-malignant and malignant gastric tissues. Reports vary as to the frequency of STn expression and its prognostic role in gastric cancer. To determine whether these differences might be due to inter-country variations in gastric cancer biology, we immunohistochemically analyzed 340 gastric cancers from 2 countries at high-risk (high incidence) for gastric cancer (Japan and Chile), one with intermediate risk (Brazil) and one with low-risk (USA). Expression of STn was correlated with clinico-pathological features of the tumors and with cancer-related survival. Regardless of country, the frequency of STn-positive tumors was lower in non-invasive ("early") than in advanced gastric cancer. Consequently, high-risk countries where early gastric cancer is more common demonstrated a lower overall frequency of STn-positive tumors. In all 4 countries, STn expression directly correlated with depth of invasion, stage, and lymph node involvement. In addition, STn expression correlated with a poor prognosis in all 4 countries, but the effect of STn on survival was not independent of tumor stage. Our findings indicate the need to consider the inherent gastric cancer risk and prevalence of early gastric cancer in the study population when reporting frequency of STn expression in gastric cancer. Regardless of country, however, STn expression is a marker of gastric cancer progression suggesting that cancer-associated mucins play a role in the malignant behavior of this tumor.

Simple mucin-type carbohydrate antigens (T, sialosyl-T, Tn and sialosyl-Tn) in breast carcinogenesis.

Immunohistochemical analysis of the expression of simple mucin-type carbohydrate antigens (Tn, sialyl-Tn and T) was performed in a series of 43 cases of intraductal hyperplasia without atypia, 9 cases of intraductal hyperplasia with atypia, 54 cases of ductal carcinoma in situ (DCIS) and 26 cases of invasive breast carcinoma. We also studied 36 cases of isolated breast normal epithelium, 20 cases of "normal" breast epithelium adjacent to neoplasms and 14 cases of apocrine metaplasia. All antigens were detected in different frequencies in normal, hyperplastic, metaplastic and neoplastic breast epithelium. Tn and sialyl-Tn are expressed more frequently in malignant than in benign breast epithelium; while Tn expression increases from normal to invasive carcinomas, sialyl-Tn increases until DCIS and drops in invasive carcinomas, suggesting that either there is a failure of a proportion of DCIS to progress to invasive carcinoma or loss of expression of sialyl-Tn when some carcinomas become invasive. The high frequency of Tn and sialyl-Tn expression in breast intraductal proliferations probably reflects incomplete glycosylation in these lesions, which is a well-known tumour-associated phenomenon and supports the assumption that such lesions are putative precursors of breast cancer. T antigen was expressed in all groups studied, but its prevalence differed significantly between normal and neoplastic epithelium. The expression of these antigens in epithelium adjacent to carcinomas is similar to that found in isolated normal breast epithelium, whereas apocrine metaplasia has a pattern of simple mucin-type glycosylation that is specific and distinct from that of the normal breast epithelium, with a high frequency of marked expression of Tn and sialyl-Tn. The similarity of the pattern of expression of simple mucin-type antigens in metaplasia and malignant neoplasia reduces the usefulness of these markers from a diagnostic standpoint.

[Gallbladder cancer: immunohistochemical expression of CA-19-9, epithelial membrane antigen, dupan-2 and carcinoembryonic antigen]. / Cancer de la vesicula biliar: expression inmunohistoquimica del CA19-9, antigeno de membrana epitelial, Dupan-2 Y antigeno carcinoembrionario.

The immunohistochemical expression of CA19-9, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA) was studied in 103 tissue samples of gallbladder cancer and 25 samples of non tumoral gallbladder lesions. CA19-9 and EMA were positive in over 90% of cancers and non tumoral lesions. Dupan-2 expression was observed in 100% of non tumoral lesions and 78% of cancers. CEA expression was observed in 12% of non tumoral lesions and 89% of cancers. The magnitude of immunohistochemical staining was moderate or intense for all antibodies, except Dupan-2. No differences were observed in the location of positive staining in superficial or deep parts of the tumor. In these lesions the positive staining was cytoplasmatic with a granular and irregular pattern; on the contrary, in the non tumoral lesions, staining was seen in the apical parts of the cell. Calculated sensitivity, specificity and positive predictive value for CEA was 89%, 88% and 96% respectively. If future studies disclose a good correlation between serological and immunohistochemical detection of this antigen, its determination would be potentially useful in clinical grounds.

Initial clinical evaluation of two murine IgG2a monoclonal antibodies for immunotherapy of gastrointestinal carcinoma.

Eleven patients with advanced gastrointestinal (GI) carcinoma were entered in Phase I initial clinical trials with IgG2a antiGI carcinoma monoclonal antibodies (MAbs) GA733 (five patients) or CO19-9 (six patients). Infusion of MAb GA733 in doses greater than 30 mg was accompanied by mild and short-lasting GI toxicity. Infused MAb GA733 was bound to each patient's tumor tissue in vivo. MAb circulated in the blood for 10-25 days. All patients developed anti-mouse antibodies between 15 and 60 days post infusion. Furthermore, all but one patient raised anti-idiotypic antibodies against MAb GA733. Following administration of 10-600 mg of MAb CO19-9, no immediate or delayed toxicity symptoms were noted. Binding of infused MAb CO19-9 to tumor cells in vivo could not be detected in any of the six patients studied. The MAb circulated in the bloodstream between 5 and 12 days. Human anti-mouse antibody was detected in sera of three patients. None of the eleven patients treated with either MAb had anti-tumor responses in this Phase I clinical trial. The strong binding reactivity of MAb GA733 to tumors in vivo suggests the use of this MAb in cancer patients with less tumor burden to determine the tumoricidal efficacy of this antibody.

Aplicaçöes clínicas do CA 125 no carcinoma de ovário / Clinical applications of CA 125 carcinoma of the ovary

De todas as ginecopatias no âmbito oncológico, nenhuma se compara, em relaçäo à gravidade, ao carcinoma de ovário. Esta peculiaridade está intimamente relaconada à sua história natural e à "proteçäo" oferecida pela cavidade peritoenal. A tentativa de se descobrir maneiras eficazes para diagnóstico precoce e controle evolutivo dessa temível enfermidade tem sido objeto persistente de estudo. Dentre as modalidades que têm revolucionado o diagnóstico e o seguimento pós-terapêutico do câncer ovariano, a utilizaçäo do antígeno oncogenético CA 125 tem merecido notável realce. O objetivo desta monografia é demonstrar a importância desse marcador bioquímico na avaliaçäo do carcinoma de ovário, procurando-se näo somente relatar os aspectos conhecidos, mas também averiguar os mais controversos. Dessa forma, os autores procuram determinar sua aplicabilidade clínica e suas falhas de acordoo com os relatos mais recentes da literatura pertinente

[Clinical applications of CA 125 carcinoma of the ovary]. / Aplicações clínicas do CA 125 no carcinoma de ovário.

Cancer of the ovary is one of the most common causes of death among gynecologic neoplasms. As it is relatively "protected" by the peritoneal cavity, there is great need of methods to improve early diagnosis and to assist with the management of patients with this disease. An important advance was observed with the application of monoclonal antibodies. After 1983, most papers have mentioned CA 125 as a biochemical marker of ovarian non-mucinous cancer. The purpose of the authors is to discuss the controversial aspects of this important marker and its role in the diagnosis and follow-up of ovarian carcinoma. All being considered, clinical applications, post-treatment follow-up, and flaws can be established.

Serum CEA and CA 19-9: potential future diagnostic or screening tests for gallbladder cancer?

The poor prognosis of gallbladder cancer and the presence of high-risk populations make the identification of a screening test for this disease very desirable. As part of an ongoing case-control study of gallbladder cancer being conducted in Mexico City, Mexico, and in La Paz, Bolivia, blood specimens were sought from all patients with cancer of the gallbladder and on controls of similar age and sex undergoing upper abdominal surgery. Each sample was analyzed for carcino-embryonic antigen (CEA) and CA 19-9. Using the specimens from Bolivia, a serum CEA cutoff of 4.0 ng/ml yielded a sensitivity of 50.0% and a specificity of 92.7%, while a serum CA 19-9 cutoff of 20.0 units/ml yielded a sensitivity of 79.4% and a specificity of 79.2%. Using ROC curve analysis, the latter was a much better test than the former (p less than 0.05). Using the tests in series or in parallel did not substantively improve the results. The specimens from Mexico were used for validation purposes, and yielded very similar results. In conclusion, serum CA 19-9 and CEA are fairly good tests for discriminating patients with gallbladder cancer from patients with gallstones and no cancer, the former being a better test than the latter. These tests may be useful in identifying disease recurrences. In addition, if a sufficiently high-risk population could be identified, this could potentially become a useful screening test for this serious disease, allowing early intervention. However, additional data are needed prior to recommending this clinically.