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J Soares

Publications and source records attributed to J Soares.

At least 37 records · Page 2Linked to original sources
PubMed2001

Karyotypic characterization of papillary thyroid carcinomas.

BACKGROUND: Cytogenetic studies performed in papillary thyroid carcinoma (PTC) identified chromosome 10q rearrangements with breakpoints at 10q11.2 as the most frequent aberrations in these tumors. In the current study, the authors aimed to identify other chromosomal abnormalities nonrandomly associated with papillary thyroid carcinomas. METHODS: Cytogenetic analysis was performed on 94 papillary thyroid carcinomas after short-term culture of the tumors sterile fragments. RESULTS: Clonal chromosomal changes were found in 37 tumors (40%). Structural cytogenetic abnormalities were observed in 18 carcinomas. Chromosomes 1, 3, 7, and 10 were the most frequently involved in rearrangements. Pooled results of the breakpoints detected in these tumors, as well as those described in the literature, allowed the authors to verify as the most common breakpoint loci 1p32-36, 1p11-13, 1q, 3p25-26, 7q34-36, and 10q11.2. The correlation between the karyotype features of the 94 PTCs and the histologic data revealed that some PTC follicular variants were characterized by chromosomal aberrations commonly found in thyroid follicular adenomas: a del(11)(q13q13), a t(2;3)(q13;p35), and gains of chromosomes 3, 5, 7, 9, 12, 14, 17, and 20. In the tall cell PTC variant group, 4 of the 7 tumors presented clonal cytogenetic changes, 3 (75%) of which were characterized by anomalies of chromosome 2 that lead to a overrepresentation of the long arm of this chromosome. Noted also in these series was an association between complex karyotypes and tumors with poorly differentiated histiotypes. CONCLUSIONS: In this study, the authors report chromosome 1p32-36, 1p11-13, 3p25-26, and 7q32-36 as novel breakpoint cluster regions in PTC, and they suggest that there are cytogenetic changes preferentially associated with the follicular and tall cell PTC variants.

Adolescent↗
PubMed2001

Cytogenetic similarities between two types of salivary gland carcinomas: adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma.

Adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) are low-grade adenocarcinomas of salivary glands with a putative common histogenesis from the intercalated ducts but featuring distinct histological appearances. Hybrid tumors containing areas with histological patterns of both neoplasms have been reported but, to our knowledge, the question of their genotypic similarity has not yet been approached. As part of an ongoing study on cytogenetic characterization of salivary gland tumors, from a group of 24 malignant neoplasms, three out of five cases of ACC and three of four cases of PLGA were selected for their similar karyotypic changes. All of them displayed chromosome 12 abnormalities, affecting the 12q12-q13 region in four (all ACC cases and one PLGA case), 12q22 in one PLGA case, and 12p12.3 in the remaining. From this group of neoplasms, one PLGA and one ACC showed the same t(6;12)(p21;q13). Our findings favor the concept that tumors of salivary glands displaying epithelial and myoepithelial phenotypes share a common histogenesis.

Adenocarcinoma↗
PubMed2001

Expression of CD44 isoforms in squamous cell carcinoma of the border of the tongue: A correlation with histological grade, pattern of stromal invasion, and cell differentiation.

BACKGROUND AND OBJECTIVES: Oral squamous cell carcinoma is a frequent disease with reserved prognosis, where the routinely evaluated morphological features lack a major correlation with prognosis. In order to assess the potential value of the immunoexpression of CD44 isoforms v3, v4-5, and v6, we studied it in a series of 56 consecutive cases of squamous cell carcinomas of the border of the tongue. METHODS: All the histological (World Health Organization grade, Bryne score, degree of keratinization, and pattern of stromal invasion) and immunohistochemistry (using monoclonal antibodies to CD44v) results were exclusively assessed at the deep invasion front of the neoplasms. Downregulation of CD44v was defined by focal or irregular staining of < 10% of the cells at the deep invasive front. RESULTS: There was downregulation of CD44v3 in 37.5% of the cases, CD44v4-5 in 67.9%, and CD44v6 in 33.9%, occurring mostly in cases with low Bryne scores and graded as well-differentiated according to the WHO classification. Downregulation of CD44v was found to correlate with cell differentiation, tumor grade, and the pattern of neoplastic invasion. CONCLUSIONS: Our findings in the present series point to the consideration that CD44v pattern and intensity of immunoexpression in the deep invasive front of squamous cell carcinoma of the tongue are mostly related to tumor grade, the features of stromal invasion, and to the presence of cervical lymph node metastases.

Adult↗
PubMed2001

The use of 99mTc-phytate for sentinel node mapping in melanoma, breast cancer and vulvar cancer: a study of 100 cases.

Sentinel node mapping reduces surgical morbidity and allows the use of more accurate tumour staging techniques. Radionuclide studies are preferentially performed using small colloids, which have limited availability in our country. The possibility of using phytate for sentinel node mapping was raised because of the similarity between its biodistribution and that of nanocolloids in the reticulo-endothelial system. In this paper we evaluated the use of 99mTc-phytate for sentinel node mapping, correlating the histopathological results with the status of the rest of the lymph node chain in different malignant tumours. A total of 100 patients were studied. group 1 consisted of 62 patients with breast cancer, group 2 of 20 patients with melanoma and group 3 of 18 patients with vulvar carcinoma. Lymph node scintigraphy was carried out after injecting 99mTc-phytate subdermally, and the sentinel node projection was marked on the skin. After 18-24 h, intraoperative sentinel node localisation was performed using a gamma probe (combined with visual localisation using patent blue dye) in 75 patients, and lymph node dissection was then carried out. Radionuclide scintigraphy identified the sentinel node in 98% of all studies. Intraoperative detection using the gamma probe was equally efficient: group 1=93% (38/41), group 2=95% (18/19) and group 3=100% (15/15). The sentinel node was involved in 41%, 31% and 20% of cases in groups 1, 2 and 3, respectively. Among the patients with positive nodes, the sentinel node was the only one affected in 53% of group 1, 50% of group 2 and 67% of group 3 cases. The method's negative predictive value was 91% in group 1 and 100% in the other groups. One false-negative study occurred in a patient who had a multifocal tumour and an intraparenchymatous lymph node; another occurred in a patient with a macroscopically affected node found during surgery. There were no side-effects related to the 99mTc-phytate. It is concluded that scintigraphic and intraoperative sentinel node identification was satisfactorily performed using 99mTc-phytate. The results were comparable to those previously described in the literature using other radiopharmaceuticals. Easy availability and low cost justify the use of phytate in our practice.

Adult↗
PubMed2001

A comparative study of the experiences of violence of English and Swedish mental health nurses.

Recent studies suggest that violence in health care environments, especially mental health care, appears to be increasing. Although there is a lack of cross-cultural studies to prove it, this increase in violence would seem to be an international phenomenon. The present study sought to compare the extent and nature of violence encountered by mental health nurses in Sweden and England. Systematic studies of violence have previously been carried out independently in both countries but this was the first attempt to compare levels of violence. Clearly defined study protocols were put in place, an operational definition of 'violence' adhered to, and random samples recruited. A specially designed questionnaire was sent to every subject (Swedish nurses n=720; English nurses n=296) enquiring about the extent of nurses' exposure to violence, the nature and severity of the violence experienced, and the effect of violence on self-esteem and job satisfaction. Significant differences were found with English nurses experiencing more violence than their Swedish counterparts. Yet support for English nurses appeared to be less good than for Swedish nurses. Reasons for the differences are discussed along with possible measures to minimise the frequency of violence against nurses and the negative effects on their work.

Adult↗
PubMed2001

C-erbB-2 oncoprotein overexpression identifies a subgroup of estrogen receptor positive (ER+) breast cancer patients with poor prognosis.

PURPOSE: To investigate the predictive value of c-erbB-2 oncoprotein expression as compared with established histopathological and cytometric indicators of disease evolution in breast carcinoma. PATIENTS AND METHODS: A short-term retrospective study was conducted on a series of 306 breast cancer patients. Classic prognostic factors included tumour size, nodal involvement, histological grading, and hormone receptor status. Flow cytometric DNA ploidy and S-phase fraction (SPF) were also assessed. A Cox proportional hazards regression model was used for multivariate statistical analysis. RESULTS: c-erbB-2 overexpression was present in 43 out of 295 (14.6%) tumours, and showed a statistically significant correlation with high histological grade, DNA aneuploidy, high SPF and lack of estrogen receptors (ER). Univariate analysis revealed its association with worse disease-free survival (DFS) and overall survival (OS). The combined evaluation of c-erbB-2 with ploidy and SPF defines a variable (P + S + c) that showed a significant correlation with disease outcome. By multivariate analysis, only nodal status (P < 0.001) and P + S + c subgrouping (group 2: P = 0.002; group 3: P = 0.001) in relation to DFS, and nodal status (P = 0.001) and DNA ploidy (P = 0.006) in relation to OS, retained independent prognostic significance. Subset analyses showed that cytometric parameters, P + S + c subgrouping and hormone receptors were significantly correlated with disease outcome in node-positive patients, whereas in node-negative subgroup no prognostic indicators were found. c-erbB-2 overexpression exhibited a trend in node-positive breast cancer (DFS: P = 0.068; OS: P = 0.086), and significant correlation with poor clinical evolution in ER positive patients (DFS: P = 0.015; OS: P = 0.004), mostly receiving tamoxifen. CONCLUSIONS: c-erbB-2 is an independent prognostic indicator of DFS when evaluated in conjunction with ploidy and SPE. It also seems to predict response to tamoxifen therapy, by identifying a subgroup of ER positive (ER+) breast cancer patients with poor prognosis.

Adult↗
PubMed2001

Male breast cancer--a reappraisal of clinical and biologic indicators of prognosis.

Between 1970 and 1998, 90 cases of male breast cancer with available pathological material were retrieved. The disease often presented in aged patients (median--66 years) and as advanced stage (stage III/IV-51%). Excluding stage IV disease, the neoplasia were predominantly ductal invasive carcinomas. NOS (not otherwise specified) (92%), grade 1 and grade 2 (94%), positive for estrogen and progesterone receptors (72% and 74%), negative for androgen receptors (100%), p53 negative (95%), c-erbB-2 negative (88%) and DNA aneuploid (73%). Assessment of disease outcome is determined by stage at time of diagnosis, and axillary lymph node status was the only parameter found to have a statistically significant correlation with either disease-free interval or overall survival (p < 0.001) by multivariate analysis. Clinically useful information on the probability of relapse can be added by determining c-erbB-2 (p = 0.02) and progesterone receptors (p = 0.04) in stage III and tumor ploidy (p = 0.04) in pN1 subgroups of patients.

Adult↗
PubMed2001

Aggressive metastatic follicular thyroid carcinoma with anaplastic transformation arising from a long-standing goiter in a patient with Pendred's syndrome.

In this article we describe detailed pathological and molecular genetics studies in a consanguineous kindred with Pendred's syndrome. The index patient was a 53-year-old female patient with congenital deafness and goiter. Her parents were first-degree cousins. She had a large goiter (150 g) that had been present since childhood. One of her sisters and a niece are also deaf and have goiter as well. The presence of Pendred's syndrome was confirmed by a positive perchlorate test and the demonstration of a Mondini malformation. Thyroid function tests (under levothyroxine [LT4] therapy) were in the euthyroid range with a thyrotropin [TSH] level of 2.8 microU/mL (0.2-3.2), a serum total thyroxine (T4) of 90 nmol/L (54-142), and a serum total triiodothyronine (T3) of 2.7 nmol/L (0.8-2.4). Total thyroidectomy was performed, and the mass in the right lobe was found to have invaded adjacent tissues. The histopathological findings were consistent with a follicular carcinoma with areas of anaplastic transformation and lung metastasis. The patient was treated twice with 100 mCi 131iodine (3,700 MBq) and received suppressive doses of LT4. Postoperatively, the serum thyroglobulin (Tg) levels remained markedly elevated (2,352 to 41,336 ng/mL). The patient died of a sudden severe episode of hemoptysis. Sequence analysis of the PDS gene performed with DNA from the two relatives with Pendred's syndrome revealed the presence of a deletion of thymidine 279 in exon 3, a point mutation that results in a frameshift and a premature stop codon at codon 96 in the pendrin molecule. We concluded that prolonged TSH stimulation because of iodine deficiency or dyshormonogenesis in combination with mutations of oncogenes and/or tumor suppressor genes, may result in the development of follicular thyroid carcinomas that undergo transformation into anaplastic cancers. It is likely that these pathogenetic mechanisms have been involved in the development of aggressive metastatic thyroid cancer in this unusual patient with Pendred's syndrome.

Adult↗
PubMed2001

Prognostic comparative study of S-phase fraction and Ki-67 index in breast carcinoma.

AIMS: To investigate the prognostic value of recently proposed flow cytometric S-phase fraction (SPF) variables (average SPF and SPF tertiles) compared with conventional SPF, and to compare the one with the best predictive value with the immunohistochemical Ki-67 index in breast carcinoma. METHODS: A short term follow up study (median, 39.6 months) of a large series of patients (n = 306) was conducted. DNA ploidy was analysed on fresh/frozen tumour samples by flow cytometry, and the SPF was calculated from the DNA histogram using an algorithm. The Ki-67 index was assessed on paraffin wax embedded material by immunohistochemistry (cut off point, 10%). The two methods were compared by means of kappa statistics, and the prognostic significance of both in relation to disease free survival (DFS) and overall survival (OS) was determined. RESULTS: SPF and Ki-67 analysis was performed on 234 (76.5%) and 295 (96.4%) tumours, respectively. The two assessments were simultaneously available in 230 cases. All SPF variables analysed in the whole series significantly correlated with disease evolution, with the conventional median SPF (cut off point, 6.1%) showing the highest predictive value in relation to both DFS (p = 0.0001) and OS (p = 0.0003). SPF tertiles and median SPF evaluated according to DNA ploidy status had no prognostic significance. The Ki-67 index showed a trend in relation to DFS (p = 0.086) that did not reach significance, and no correlation with OS was found (p = 0.264). The comparative analysis of SPF and Ki-67 revealed some agreement between the two methods (agreement, 69.13%; kappa statistic, 0.3844; p < 0.001), especially in the subgroup of diploid tumours. CONCLUSIONS: Flow cytometric SPF is a better prognosticator than the Ki-67 index, but only SPF variables applied in the whole series show potential clinical usefulness.

Adult↗
PubMed2000

Four novel MSH2 / MLH1 gene mutations in portuguese HNPCC families.

Hereditary non-polyposis colorectal cancer (HNPCC) is considered to be determined by germline mutations in the mismatch repair (MMR) genes, especially MSH2 and MLH1. While screening for mutations in these two genes in HNPCC portuguese families, 3 previously unreported MSH2 and 1 MLH1 mutations have been identified in families meeting strict Amsterdam criteria. Hum Mutat 15:116, 2000.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Immunohistochemical detection of mismatch repair gene proteins as a useful tool for the identification of colorectal carcinoma with the mutator phenotype.

There are two well-defined pathways for colorectal carcinogenesis, the suppressor and the mutator pathways. The latter is characteristic of hereditary non-polyposis colorectal cancer (HNPCC), but can also be found in a subset of sporadic colorectal cancer (SCC) possessing distinctive clinical and pathological features, namely early age of onset, location in the right colon, poor differentiation, and a predominant mucinous component. This mutator pathway results from inactivation of mismatch repair (MMR) genes, namely MSH2 and MLH1. The aim of this study was to ascertain if abnormal MMR protein gene expression is a good indicator for identifying tumours from the mutator pathway. Seventy-six cases of SCC were studied by immunohistochemistry using two monoclonal mouse antibodies that react against MSH2 and MLH1 protein gene products. Immunoexpression was assessed both in tumour and in non-neoplastic, adjacent and distant mucosa. Microsatellite instability (MSI) was detected by evaluating the length of poly(CA) repeated sequences at seven loci, or by the detection of small unstable alleles in a poly(A) repeat - BAT-26. Except for BAT-26, in which only tumour DNA was used, MSI analysis was performed in both tumour and normal mucosal DNA. MSI was classified as high (MSI-H), low (MSI-L) or stable (MSS). Abnormal protein expression was found in 9/76 (12%) tumours. Immunohistochemistry for hmlh1 and hmsh2 detected 75% of MSI-H. There was also a highly significant correlation between the observed immunoexpression and several clinical and pathological characteristics described as the phenotypic profile of the mutator pathway, such as right-sided location (p=0.003), mucin production (p=0.008), and a peritumoural lymphoid infiltrate (p=0.009). Non-neoplastic adjacent mucosa showed normal hMSH2 expression in all cases, but in ten cases there was no hMLH1 expression in this transitional mucosa, which is known to display an alterated mucin pattern and a high proliferative rate. These results demonstrated a good correlation between hMLH1 and hMSH2 gene immunoexpression and the clinico-pathological features characteristic of the mutator phenotype and support the use of this method as a rapid and efficient way to detect tumours arising from this pathway.

Adult↗
PubMed2000

Eleven novel APC mutations identified in Portuguese FAP families.

Germline mutations of the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominant predisposition to colorectal cancer. In the present study we screened all of the exons of the APC gene in individuals belonging to 85 Portuguese FAP families. We here report eleven novel mutations which are predominantly frameshifts or single base substitutions, resulting in premature stop codons. Hum Mutat 16:178, 2000.

Adenomatous Polyposis Coli↗
PubMed2000

Expression of CD44 isoforms in normal salivary gland tissue: an immunohistochemical and ultrastructural study.

We studied the expression of CD44 isoforms immunoreactivity in normal human salivary gland tissue, aiming at its full characterisation in normal epithelial and myoepithelial cell types. Optical immunohistochemistry techniques using monoclonal antibodies anti-CD44v3, CD44v4/5 and, for CD44v6, together with immunoelectron microscopy, were performed in serous, seromucinous and mucinous glands. Normal human breast and a case of lactating breast adenoma were used for comparative purposes and as controls. CD44v3 was positive in acinar and myoepithelial cells and was absent in mucin-producing cells from the different gland types. CD44v4/5 was consistently negative in all types of salivary tissue. CD44v6 was constantly positive in serous acinar cells, focally positive in basal cells of ducts, and myoepithelial cells consistently expressed it. At the ultrastructural level, CD44v6 was localised to the interdigitating processes of acinar cells, whenever they were not covered by basal lamina and to the cell membrane facing myoepithelial cells. In myoepithelial cells, immunolabelling was found at the membranes facing the acinar cells and in caveolae present at this interface. No labelling was found at cell membranes of both acinar and myoepithelial cells in contact with basal lamina or at the luminal aspect of the former. The finding of CD44v3 and v6 in myoepithelium of normal salivary glands may argue in favour of the role of these molecules in the regulation of growth and renewal of normal tissues and, potentially, on the morphogenesis of salivary gland neoplasms.

Breast Neoplasms↗
PubMed2000

Objective biologic parameters and their clinical relevance in assessing salivary gland neoplasms.

This review summarizes research advances of cytometric, proliferation, cytogenetic, and molecular "objective" measurable parameters, as additional aids to prognostic information of salivary gland tumors provided by classical clinicopathologic indicators. Flow cytometric DNA ploidy and S-phase fraction seem to be of value as predictors of tumor behavior, aneuploidy, and high S-phase identifying an unfavorable clinical evolution of salivary gland neoplasms. Cell proliferation markers assessed by immunohistochemistry (e.g., PCNA, Ki-67) also appear to have predictive significance, but some conflicting results, in part related to technical procedures, limit their routine clinical application. Silver-stained methods (AgNORs) show a scarce value in estimating prognosis of salivary gland malignancies. p53 and c-erbB-2 as well as karyotyping, are of disputable benefit for clinical use, but the biologic information they provide give a better understanding on the molecular mechanisms involved in the development and progression of tumors. Further studies, with large databases, long follow-up information, uniformized histologic classification, and standardized methodologies, are needed to establish how these "objective" parameters would be of truly beneficial for the treatment of patients with salivary gland tumors.

Biomarkers, Tumor↗
PubMed2000

Presence of a Gs alpha mutation in an adrenal tumor expressing LH/hCG receptors and clinically associated with Cushing's syndrome.

We describe the case of a patient with Cushing's syndrome due to a functioning adrenal adenoma. There was a pronounced increase in serum and urinary cortisol after administration of human chorionic gonadotropin. Immunocytochemistry revealed positive immunostaining for LH/hCG receptors. Molecular analysis documented the presence of a gsp mutation at codon 201 (CGT to TGT). The existence of this type of hCG-responsive adrenal tumor may help explain the higher prevalence of cortisol-secreting adrenal tumors versus pituitary-dependent disease in pregnant women with Cushing's syndrome as well as some reported cases of remission following delivery.

Adenoma↗