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Biomedical subjects

M Sobrinho-Simões

Publications and source records attributed to M Sobrinho-Simões.

At least 19 recordsLinked to original sources

Loss of Y chromosome in gastric carcinoma. Fact or artifact?

Loss of chromosome Y has been reported in gastric cancer cells together with other chromosomal abnormalities. We noted loss of chromosome Y and near-diploid karyotypes in five cases of gastric adenocarcinoma, but DNA flow cytometry performed on fresh tumor tissue showed aneuploid peaks in four of them. Our findings suggest that loss of the Y chromosome in gastric cancer probably reflects the karyotype of a subpopulation of stromal cells and not a neoplasia-related chromosomal aberration.

Adult

Immunohistochemical analysis of ras oncogene p21 product in human gastric carcinomas and their adjacent mucosas.

In an attempt to clarify the relationship between ras oncogene expression and the clinico-pathological features of malignant and pre-malignant lesions of the stomach we undertook the immunohistochemical study of the expression of ras gene p21 product in a series of eighty gastric carcinomas and their respective adjacent mucosas. In two cases the mRNA of Ha-ras was also studied by in situ hybridization. The majority of gastric carcinomas as well as their adjacent non-neoplastic mucosas expressed ras gene product. There was a significant relationship between the expression of ras gene p21 product and the morphologic pattern of the tumours. An enhanced ras expression was found in several conditions regarded as precursor lesions of intestinal and/or diffuse types of gastric carcinoma (dysplasia, foveolar hyperplasia and even the neck zone of normal-appearing gastric glands, namely in the mucosa adjacent to diffuse carcinomas). Ras expression was actually more prominent in most of these conditions than in their respective adjacent carcinomas. No significant relationship was found between ras expression and invasiveness of the wall, nodal metastases and venous invasion.

DNA, Neoplasm

P53 mutations in gastric carcinomas.

We carried out an immunohistochemical study and DNA analysis of 30 gastric carcinomas to evaluate p53 overexpression and allelic loss at 17p. The immunohistochemical study demonstrated immunoreactivity for p53 protein in four cases. Allelic loss for the pYNZ22.1 marker was detected in nine cases. In total, ten cases showed immunoreactivity for p53 protein, allelic loss, or both. The study of nine of these cases by constant denaturant gel electrophoresis revealed p53 mutations in three cases. We conclude that the prevalence of mutations of p53 in our series is similar to what has recently been observed in other cases of gastric cancer, but lower than in colon carcinomas.

Alleles

c-erbB-2 expression in primary gastric carcinomas and their metastases.

In an attempt to evaluate the relationship between c-erbB-2 expression and/or gene amplification, DNA ploidy and morphology, wall penetration, lymphatic permeation, and vascular invasion, we studied a series of 87 primary gastric carcinomas and their respective metastases (n = 335) using immunohistochemistry and performed DNA analysis of 30 primary tumors and 10 metastases from eight cases. Flow cytometry of fresh or frozen material was performed in 79 primary tumors. Five out of 87 primary tumors (5.7%) and 17 out of 335 lymph node metastases (5.1%) showed unequivocal membrane immunostaining for c-erbB-2. Seven out of 30 primary tumors (23.3%) showed gene amplification while amplification was identified in four out of 10 metastases (40.0%) from three patients. Eight tumors (9.2%) showed c-erbB-2 protein immunoreactivity, gene amplification, or both. One of these cases showed c-erbB-2 protein immunoreactivity only in the metastatic deposits, while gene amplification could be identified in the primary tumor. Three primary tumors showed gene amplification, but immunoreactive cells could not be identified. In no case was protein overexpression identified in the absence of gene amplification. Five cases with c-erbB-2 expression/amplification were well/moderately differentiated, and all the eight cases with c-erbB-2 expression/amplification disclosed aggressive features. Lymphatic permeation/lymph node metastases were found in all the cases and seven cases showed vascular invasion as well. In one case, there was also a liver metastasis. Two cases were early gastric carcinomas (T1sm) showing lymphatic permeation/nodal metastases and venous invasion. Six cases were aneuploid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn and T) in gastric mucosa, carcinomas and metastases.

Immunohistochemical study of the expression of simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, T and sialosyl-T) was performed using specific monoclonal antibodies in the mucosa adjacent to gastric carcinomas histologically appearing unaffected (n = 58), and in primary gastric carcinomas (n = 87) and their metastases (329 lymph nodes and two liver metastases). Normal-looking mucosas: Tn antigen expression was identified in all the cases; sialosyl-Tn in eight cases; T antigen was never expressed and sialosyl-T antigen was observed in four cases; the expression of these antigens was distinctly limited to the cytoplasm, mostly in the supranuclear (Golgi) area. All the mucosas with intestinal metaplasia showed sialosyl-Tn expression in the goblet cells. Gastric carcinomas: 80 cases (91.9%) stained for Tn antigen, 69 cases (19.3%) expressed sialosyl-Tn antigen, 18 cases (20.7%) expressed T antigen and 17 cases (19.5%) stained for sialosyl-T antigen. In contrast to normal mucosa, carcinoma cells expressed simple mucin-type antigens both at the cytoplasm and at the cell membrane. Most primary carcinomas were concurrently stained for Tn and sialosyl-Tn antigens alone (41.1%), or together with T antigen or sialosyl-T antigen (28.7%). We found a close relationship between the expression of simple mucin-type carbohydrate antigens in the primary tumours and their respective metastases. T antigen (and sialosyl-T antigen) expression was correlated with the wall invasiveness of the tumours. The 18 tumours expressing T antigen and 16 out of the 17 tumours expressing sialosyl-T antigen had nodal metastases and/or sialosyl-Tn expression and the aggressiveness of the tumours (wall penetration, lymph node metastasis and venous invasion). No significant differences were observed between positive and negative tumours for Tn, sialosyl-Tn, T and sialosyl-T antigens regarding the morphologic at type, growth pattern, ploidy or lymphoid infiltrate of the primary tumours.

Antibodies, Monoclonal

Familial gastric polyposis revisited. Autosomal dominant inheritance confirmed.

We update and review a large pedigree originally described by Santos and Magalhães with familial gastric polyposis and a high incidence of gastric cancer. The present observation of male-to-male transmission of the disease clearly demonstrates the autosomal dominant pattern of inheritance. The histologic review of the polyps present in several members of the family allowed the diagnosis of hyperplastic polyposis. Eight members of the family (two with concomitant gastric pathology) have severe cutaneous psoriasis. This finding may represent the existence of two different disorders segregating in the family or, alternatively, pleiotropic manifestations of the same gene.

Adenocarcinoma, Mucinous

Ultrastructural and electron immunohistochemical features of medullary thyroid carcinoma.

An ultrastructural study, both morphological and immunohistochemical, has been carried out on eight thyroglobulin-positive and nine thyroglobulin-negative medullary carcinomas of the thyroid. The morphometric analysis of granule size showed that all tumours contained cells with small granules and cells with medium size granules, whereas eight tumours had additional cells with large granules. The small granules had an electron dense core, while the medium and large sized granules were both pale-cored and dense-cored. The cells with small, medium or large secretory granules were all immunoreactive for calcitonin and CGRP. No ultrastructural differences were observed between thyroglobulin-positive and thyroglobulin-negative cases of medullary carcinoma of the thyroid.

Adult

Diffuse sclerosing variant of papillary thyroid carcinoma. A clinicopathologic study of 10 cases.

The clinico-pathologic features of ten cases of the diffuse sclerosing variant (DSV) of papillary carcinoma of the thyroid (PCT) are presented and compared with those of 259 common PCT diagnosed during the same period at the Instituto Português de Oncologia (Centro de Lisboa). The primary therapeutic approach was basically the same in every case and follow-up information was obtained in every patient. DSV comprises 3.4% of our series of PCT. Patients with DSV are suggestively younger (34.7 +/- 19.9), than those with common PCT (42.3 +/- 16.1) regional lymph node metastases and distant metastases are significantly greater in DSV (100.0% and 50.0%, respectively) than in common PCT (38.6% and 14.3%, respectively). No significant differences were found between the two groups with regard to sex-ratio, extrathyroid invasion and mortality rate. No differences were either found regarding the immunohistochemical results: neoplastic cells of both groups showed immunoreactivity with antisera for thyroglobulin, epidermal keratins, S-100 protein and NSE. Some foci of three DSV cases displayed histological and histochemical features resembling those of the so-called mucoepidermoid carcinoma. It is concluded that a) DSV is an exceptional example of PCT in which most of the usual morphologic features of this type of carcinoma are overexpressed; b) DSV is not exclusively found in young patients and, in older patients, merges with other variants of PCT; c) DSV is indeed a more aggressive tumor than common PCT and should therefore be treated accordingly regardless of the age of the patients.

Adolescent

Carcinoembryonic antigen in medullary thyroid carcinoma: an immunohistochemical study applying six novel monoclonal antibodies.

Six novel mouse monoclonal antibodies raised against carcinoembryonic antigen (CEA) were used to study 22 medullary, ten papillary, ten follicular, and eight anaplastic thyroid carcinomas. The antibodies CEA 12-140-5, -7, and -10 reacted with the same epitope group (GOLD 4), whereas antibodies CEA 12-140-1, -2, and -4 recognized different epitopes (GOLD 5, 2 and 1, respectively) on the CEA molecule. All medullary carcinomas of the thyroid (MCTs) were stained when the antibodies CEA 12-140-5, -7, and -10 were applied, whereas CEA 12-140-1 stained all but five MCTs; CEA 12-140-2 and CEA-12-140 -4 each stained all but two. The CEA immunoreactivity was predominantly located diffusely in the cytoplasm but occasionally was also concentrated along the cell membrane. CEA immunoreactivity was also observed in normal C-cells and C-cell nodules. The follicular, papillary, and anaplastic carcinomas were all CEA-negative with the monoclonal antibodies applied in this study. The differences in staining pattern of MCTs found with the various antibodies may be explained as a lack of expression of some epitopes in some tumors, or they may be due to a varying degree of masking of the epitopes by the extensive glycosylation of CEA and CEA-like substances.

Adolescent

Follicular and papillary variants of medullary carcinoma of the thyroid.

Two medullary carcinomas of the thyroid (MCT) with relatively unusual patterns are reported. The first was an aggressive tumour which occurred in a 66-year-old man and displayed in most areas follicular structures. The second tumour occurred in a 36-year-old woman, followed a benign course and showed papillary infoldings lined by multilayered neoplastic cells. The search for thyroglobulin yielded negative results whereas calcitonin immunoreactivity could be found in most neoplastic cells of both tumours. The diagnosis of MCT was further substantiated by the presence of scarce amyloid deposits and typical neuro-secretory granules by electron microscopy. These cases demonstrate once more that follicular and papillary structures can be a prominent feature of some MCTs reinforcing therefore the major role of immunocytochemistry in the differential diagnosis of thyroid carcinomas. Papillary MCT seems to carry a good prognosis in contrast to follicular MCT if one takes into account the follow-up data of the present cases together with those of similar cases reported in the literature; the whole series is nevertheless too small to allow for definite conclusions on this matter.

Adult

Columnar-cell carcinoma. Another variant of poorly differentiated carcinoma of the thyroid.

An unusual case of poorly differentiated carcinoma of the thyroid is reported. The tumor occurred in a 60-year-old man, who died with widespread metastases 5.5 years after primary treatment. The unencapsulated tumor measured 8 X 5 X 9.5 cm and was composed of columnar cells. Two to three mitotic figures per 10 high-power fields were present. The cells were thyroglobulin positive and not stained for calcitonin and carcinoembryonic antigen (CEA). The light microscopic appearance was similar to that of a metastasis from a carcinoma of the bowel. The authors conclude that columnar cell carcinoma is a separate type of thyroid carcinoma that shares the clinical properties of both follicular and papillary carcinoma and carries a poor prognosis. However, for practical purposes, the authors think that the tumor should be included in the category of poorly differentiated thyroid carcinomas together with the so-called insular carcinomas, mucoepidermoid carcinomas, and mucinous carcinomas.

Carcinoma

Thyroid antibodies.

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Antigens, Neoplasm

Medullary thyroid carcinoma with thyroglobulin immunoreactivity. A special entity?

Fourteen medullary carcinomas of the thyroid (MCT) immunoreactive for both thyroglobulin and calcitonin were studied by light microscopy and immunohistochemistry. Thyroglobulin immunoreactivity was seen in neoplastic follicles and/or in solid foci in the lymph node metastases of two cases. Colocalization of thyroglobulin and calcitonin was found in the same neoplastic cells of eight cases using a double immunostaining method; in three of these (including one with metastases), thyroglobulin was found to be colocalized with calcitonin gene related peptide as well. Our histological and immunohistochemical results support the assumption that MCT with thyroglobulin immunoreactivity is an unusual variant of the multihormone producing MCT and strengthen the hypothesis that a common stem cell is the origin of these tumors. The available clinical data suggest that thyroglobulin-positive MCT carry a better prognosis than thyroglobulin-negative MCT.

Adult