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M Sobrinho-Simões

Publications and source records attributed to M Sobrinho-Simões.

At least 73 records · Page 4Linked to original sources
PubMed1997

MUC1 gene polymorphism and gastric cancer--an epidemiological study.

Gastric carcinoma is a major cause of cancer death worldwide and, like most human cancers, probably develops after environmental insults acting on normal individuals and/or individuals with increased genetic susceptibility. Mucins are attractive molecules to study the relationship between genetics and environment because they play an important role in the protection of gastric mucosa against environmental insults and exhibit a highly polymorphic genetic variation. We performed a case-control study using Southern blot analysis to evaluate the MUC1 gene polymorphism in a series of blood donors (n = 324) and in patients with gastric carcinoma (n = 159). We found that the distribution of MUC1 alleles is significantly different in the two populations and that small MUC1 alleles and small MUC1 genotypes are significantly more frequent in patients with gastric carcinoma than in controls. Individuals with small MUC1 genotypes are at increased risk for gastric carcinoma development.

ABO Blood-Group System↗
PubMed1997

Expression of stratified epithelial-type cytokeratins in hyalinizing trabecular adenomas supports their relationship with papillary carcinomas of the thyroid.

AIM: To evaluate the cytokeratin pattern of expression of hyalinizing trabecular adenomas and to verify whether or not these tumours, that share morphological features with papillary carcinomas, present the stratified epithelial-type cytokeratins commonly found in ordinary papillary carcinomas. METHODS AND RESULTS: This study consisted of the immunohistochemical detection of simple and stratified epithelial type cytokeratin filaments in a series of six hyalinizing trabecular adenomas, three papillary carcinomas with a trabecular growth pattern and two carcinomas combining hyalinizing trabecular and papillary patterns. Simple epithelial-type cytokeratins 7, 8, 18 and 19 were found in every case. Expression of the stratified epithelial-type cytokeratins 1, 5/6 and/or 13 was detected in four hyalinizing trabecular adenomas. CONCLUSION: Based on this, as well as on the cytological features and on the frequent co-occurrence of hyalinizing trabecular adenoma and papillary carcinoma, we suggest that the former lesion may be considered a peculiar encapsulated variant of papillary carcinoma.

Adenoma↗
PubMed1997

Prognostic factors in thyroid carcinomas.

The AA review the so-called prognostic factors in thyroid carcinoma taking in consideration four of the five major histotypes of thyroid tumours: Papillary ca. (5-year-survival -91%), follicular ca. (73%), poorly differentiated ca. (48%) and undifferentiated ca. (0%), with an emphasis on papillary carcinoma. The prognostic factors are described in two major groups: Clinicopathologic factors comprising the classic clinicopathologic features--age, gender, size, extrathyroidal extension, vascular invasion, nodal metastization and distant metastization--and Biologic factors, comprising a group of heterogeneous and less classic features such as DNA content and proliferation markers, oncogenes and tumour-suppressor genes, growth factors and growth factor receptors, pro- and anti-apoptotic genes, mucin and histo-blood group antigens, cytoskeletal filaments, adhesion molecules, and so forth. Finally, the AA address briefly a third group of (prognostic) factors that reflect the interaction between the neoplastic cells and their microenvironment: extracellular matrix and proteolytic enzymes (laminin, collagen IV, fibronectin, collagenases, alpha-1 anti-trypsin) and lymphocytic infiltration (S-100 positive cells, IGF-I and IGF-I receptor).

Adenocarcinoma, Follicular↗
PubMed1996

Establishment and characterization of two cell lines derived from human diffuse gastric carcinomas xenografted in nude mice.

Two human diffuse gastric carcinoma cell lines were established in vitro from xenografted tumours serially passaged in nude mice. Of 12 primary diffuse gastric carcinomas, 7 were successfully xenografted in nude mice (58.3%). Short-term primary cultures were achieved in all the xenografted lines. However, only 2 of the 7 short-term primary cultures were established as long-term cultures (GP202 and GP220). GP202 cells are larger than GP220 cells, show less abundant intercellular junctions at the ultrastructural level and grow in culture as a compact thin monolayer. The GP220 cells grow preferentially in small clusters attached to the monolayer, with a subpopulation of floating cells. Both lines have cells containing small mucin vacuoles in the cytoplasm and cells displaying a typical signet-ring shape. GP202 cells grow as solid tumours in nude mice but GP220 cells do not give rise to tumours. The flow cytometry and karyotype analysis showed aneuploidy in GP202 cells, with many numerical and structural chromosomal abnormalities, and diploidy in GP220 cells, with several structural chromosomal abnormalities. The CDw75 and Tn antigens are more prominently expressed in GP202 cells than in GP220 cells. T antigen is only expressed in GP202 cells, whereas only GP220 cells express EGFR. Sialosyl-Tn is not expressed in either of the cell lines. The gastric cancer cell lines described in this paper represent a valuable addition to the small number of diffuse gastric cancer cell lines currently available and also provide a good model for further in vitro and in vivo studies of gastric carcinogenesis.

Adenocarcinoma↗
PubMed1996

pS2 protein expression in gastric carcinoma. An immunohistochemical and immunoradiometric study.

The aim of this study was to examine the prevalence of pS2 expression in gastric carcinoma and to determine its prognostic significance. We analysed pS2 protein expression in 50 gastric carcinomas and respective adjacent mucosas by immunohistochemistry and immunoradiometric assay (IRMA). pS2 was consistently expressed in superficial and foveolar epithelium of non-neoplastic mucosa and in 66.0% of the carcinomas. pS2 immunoreactivity was significantly higher in diffuse than in intestinal carcinomas, and in those cases with nodal metastases than in those without. No correlation was found between pS2 immunostaining and gender, age, staging, depth of wall penetration, venous invasion, ploidy and S-phase fraction. The mean levels of pS2 (IRMA) were significantly lower in gastric carcinomas than in non-neoplastic mucosas, and were not correlated with any of the aforementioned clinicopathological features. The survival of patients with pS2-positive tumours was not significantly different from that of patients with pS2-negative tumours. We conclude that pS2 expression, which can be used as a marker of gastric-type differentiation, is associated with gastric carcinoma of diffuse type. The lack of correlation between pS2 expression and most features of tumor aggressiveness and patients' survival precludes its use as a prognostic tool in gastric carcinoma.

Adenocarcinoma↗
PubMed1996

Microsatellite instability at multiple loci in gastric carcinoma: clinicopathologic implications and prognosis.

BACKGROUND & AIMS: Microsatellite instability (replication error [RER]-positive phenotype) is a frequent genetic alteration in gastric carcinomas. The clinical relationship between RER-positive and RER-negative gastric tumors is poorly characterized. The aim of this study was to investigate the relationship between the number of altered microsatellite loci and the clinicopathologic features of gastric carcinoma. METHODS: Five or 6 microsatellite loci were analyzed in 61 gastric carcinomas using polymerase chain reaction. RESULTS: Twenty-one carcinomas (34.4%) had microsatellite instability: 7 at 1 locus, 2 at 2 loci, and 12 at multiple loci. The comparison between the three groups (with none, 1 or 2, and more than 2 RER-positive loci) showed that RER-negative carcinomas and carcinomas with 1 or 2 RER-positive loci share features that differ from those of carcinomas with multiple RER-positive loci. The latter were all of the intestinal or atypical subtype and had lower DNA content, more prominent lymphoid infiltration, and less prevalent nodal metastases than carcinomas in the other two groups. The patients with carcinomas showing multiple RER-positive loci had a better prognosis. CONCLUSIONS: The finding of microsatellite instability in a single or few loci does not qualify a case as a mutator phenotype from a clinical standpoint. Gastric tumors with multiple RER-positive loci have a particular clinicopathologic profile leading to a better outcome.

Carcinoma↗
PubMed1996

Pattern of pS2 protein expression in premalignant and malignant lesions of gastric mucosa.

The aim of this study was to evaluate the pattern of pS2 protein expression in premalignant and malignant lesions of gastric epithelium. We analysed, by immunohistochemistry, the pS2 expression in six samples of normal gastric mucosa, 18 cases of chronic atrophic gastritis with intestinal metaplasia (IM), 10 hyperplastic polyps, 11 adenomatous polyps and 50 gastric carcinomas, together with the respective samples of adjacent non-neoplastic mucosa. pS2 is expressed throughout foveolar and superficial epithelium of normal gastric mucosa and this pattern is retained in chronic atrophic gastritis out of IM lesions. pS2 expression is confined to goblet cells in complete IM and occurs both in goblet and columnar cells in incomplete IM. Hyperplastic polyps displayed significantly higher pS2 expression than adenomatous polyps. In gastric carcinomas, pS2 expression was observed in 66.0% of cases, being significantly higher in diffuse (88.9%) than intestinal type carcinomas (53.6%). A subset of carcinomas of the latter group displayed pS2 immunoreactivity in a high percentage of cells with a pattern similar to that of hyperplastic polyps. Our results demonstrate there are major changes in pS2 expression, which can be used as a marker of gastric-type differentiation during the process of gastric carcinogenesis, and support the existence of at least two pathways of malignant transformation of gastric mucosa: one via intestinal metaplasia and adenomatous dysplasia, leading to glandular carcinomas with intestinal-type differentiation, the other via hyperplastic changes or de novo changes, leading to diffuse carcinomas and to a subset of glandular carcinomas displaying gastric-type differentiation.

Biomarkers, Tumor↗
PubMed1995

Increasing levels of MYC and MET co-amplification during tumor progression of a case of gastric cancer.

The cytogenetic study of a nodal metastasis from a gastric carcinoma, after two passages in nude mice, revealed a large number of double minutes. Comparative genomic in situ hybridization (CGH) analysis using DNA extracted from this xenograft revealed the existence of three clear amplification units that originated from the chromosomal subregions 6q24-25, 7q31-32, and 8q24 in the xenograft DNA. Similar, though less prominent, CGH results were found with DNAs extracted from the primary tumor and its metastasis, implying that the same amplicons were also present, albeit less abundantly, in the DNAs of these neoplastic tissues. Southern analysis of the second-passage xenograft detected 18- and 10-fold amplification of MET (located at 7q31) and MYC (located at 8q24), respectively. The retrospective study of the first passage of the xenograft, as well as of the metastatic and primary tumors before xenografting, showed amplification levels of MET of, respectively, 12-, 9-, and 5-fold and MYC of, respectively, 8-, 7-, and 5-fold. Our results suggest that increased levels of co-amplification of MYC and MET correlate with enhanced growth potential in this case of gastric carcinoma.

Adult↗
PubMed1995

Sporadic gastric carcinomas with microsatellite instability display a particular clinicopathologic profile.

Mutations in recently identified genes on chromosomes 2 and 3 seem to be responsible for repair errors (RER+) throughout the genome. This novel genetic mechanism was first reported in hereditary non-polyposis colorectal cancer syndrome and in cancers that are characteristic of this syndrome, such as carcinomas of the right colon, stomach and endometrium. We investigated the frequency of RER+ phenotype in a series of 34 sporadic gastric carcinomas, in an attempt to see if the RER+ cases displayed any particular morphologic features and/or if they showed distinctive clinicopathologic characteristics. Twelve loci were investigated. We found 23 RER- cases (67.6%) and 11 RER+ cases (32.4%). A significant association was found between RER+ carcinomas and localization of the tumors: 9 of the 11 RER+ carcinomas (81.8%) were located at the antrum whereas all the cardiac tumors were RER-. The RER+ phenotype was also significantly related to the presence of moderate/abundant T-cell lymphoid infiltration within the tumors. The 3-year survival rate of patients with RER+ tumors was suggestively longer than that of patients with RER- tumors. No significant relationship was found between several clinicopathologic characteristics of the cases, including age, sex, staging, histologic type and ploidy, despite a trend towards an association between RER+ phenotype and advanced age of the patients and poorly differentiated, intestinal type of the carcinomas. The high frequency of microsatellite instability in sporadic gastric carcinomas supports the involvement of this genetic mechanism in gastric carcinogenesis. Gastric carcinomas with the RER+ phenotype tend to occur as poorly differentiated adenocarcinomas in the antrum of elderly patients, display abundant T-cell infiltration and carry a relatively good prognosis.

Adult↗
PubMed1995

New elements for an updated classification of the carcinomas of the stomach.

Based upon the results of a thorough study of 213 patients submitted to potentially curative resection we propose the following histologic classification of gastric carcinoma: isolated-cell carcinoma (6.6%), glandular carcinoma (41.8%), solid carcinoma (13.1%) and mixed carcinoma (38.5%). Half of the mixed carcinomas displayed a predominant isolated-cell pattern, whereas in the other half the isolated-cells were a minor component (the predominant component being either glandular, solid, or both). The survival of patients with mixed carcinomas is significantly worse than those of patients with other histologic types of gastric carcinoma regardless of the site of tumors and the inclusion, or not, in the series, of post-operative deaths. The proposed classification keeps its independent prognostic significance in a multifactorial analysis, appearing as the second most important prognostic factor in patients with gastric carcinomas, after the TNM staging and before venous invasion.

Adult↗
PubMed1995

Recent advances in cytometry, cytogenetics and molecular genetics of thyroid tumours and tumour-like lesions.

In this review we summarize the most recent advances of flow and image cytometry, cytogenetics and molecular genetics of tumours and tumour-like lesions of the thyroid, especially focusing on the putative relationship between nodular goitres and adenomas, the differential diagnosis of benign and malignant neoplasms and the pathogenesis and prognosis of carcinomas. Data obtained by in situ hybridization and immunohistochemical detection of proliferative markers, metal binding proteins and oncogenes, anti-oncogenes, growth factors and growth factor receptors are also used whenever appropriate.

Cytogenetics↗
PubMed1995

Diagnostic problems in differentiated carcinomas of the thyroid.

In this review article we consecutively address the following issues: differential diagnosis of follicular adenomas and minimally invasive follicular carcinomas, with a special emphasis on the hyalinizing trabecular tumours; differential diagnosis of benign and malignant papillary lesions; individualization of the variants of papillary carcinoma that carry a guarded prognosis; differential diagnosis of differentiated thyroid carcinomas exhibiting foci of other types of thyroid carcinoma, namely mucoepidermoid and poorly differentiated carcinoma; and, finally, the diagnostic problems raised by the so-called mixed medullary-follicular carcinomas.

Diagnosis, Differential↗
PubMed1995

Papillary and mucoepidermoid carcinoma of the thyroid with anaplastic transformation: a case report with histologic and immunohistochemical findings that support a provocative histogenetic hypothesis.

A unique thyroid tumor in a 62-year-old woman is reported. Foci of papillary carcinoma (PC), mucoepidermoid carcinoma (MEC) and undifferentiated carcinoma (UC) were found in the surgical specimen. Acid mucosubstances were observed in the two histologically differentiated areas of the neoplasia. The PC showed immunoreactivity for thyroglobulin, and both PC and MEC foci were positive for high-molecular-weight keratins. Papillary carcinoma, MEC and UC were stained with antibodies against keratin CAM 5.2, vimentin, S-100 protein and neuron-specific enolase. No immunoreactivity was found for calcitonin, calcitonin-gene-related peptide, chromogranin, keratin 1, carcinoembryonic antigen and p53 suppressor gene. The diagnosis of this peculiar carcinoma of the thyroid exhibiting papillary and mucoepidermoid features together with undifferentiated (anaplastic) areas, reinforces the existence of a close relationship between papillary carcinoma and mucoepidermoid carcinoma, and supports the importance that ultimobranchial multipotential stem cells may have in the histogenesis of thyroid carcinomas.

Carcinoma, Mucoepidermoid↗