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Jorge Soares

Publications and source records attributed to Jorge Soares.

15 recordsLinked to original sources
PubMed2006

[Pneumocystis jiroveci infection in immunocompetent patients with pulmonary disorders, in Portugal].

The use of molecular tools with a great capacity to detect and differentiate strains of Pneumocystis has resulted: in the identification of low numbers of P. jiroveci organisms in clinically silent, colonized, immunocompromised patients and in immunocompetent persons. Considering this information, the aim of this study was to determine the prevalence of P. jiroveci carriers (subclinical infections) in Portuguese patients with pulmonary disorders and in healthy individuals. A total of 45 pulmonary specimens were collected from 45 immunocompetent adults with pulmonary disorders, and 37 oral washings from 37 healthy adults, between March 2001 and February 2004. All samples were analysed by indirect immunofluorescence with monoclonal antibodies and by amplification of the LSU mtrRNA by nested PCR. The results obtained in this study indicate that: 1) P. jiroveci is frequently detected (24.4%) in patients with pulmonary disorders in Portugal; 2) this population might play a role in circulation and transmission of P. jiroveci organisms in the community; 3) patients receiving corticosteroids are more likely to have detectable P. jiroveci in lungs (18%) than patients who are not receiving this immunosuppressor (12%); 4) P. jiroveci is infrequently detected in healthy adults. This may be due to very low numbers of latent organisms present in the lungs of healthy adults, difficulty in detecting few organisms, or due to the type of samples used. Screening of these individuals and notification of the results to their physician might be important: for further follow-up and whether or not prophylaxis or treatment should be prescribed; and for the clarification of the epidemiology of P. jiroveci asymptomatic infections.

Adult↗
PubMed2006

Evaluation of ERBB2 gene status and chromosome 17 anomalies in male breast cancer.

Male breast cancer (MBC) is an uncommon neoplasm that shares several biologic characteristics with its female counterpart. In the latter, abnormalities in the expression and/or copy number of the ERBB2 gene are present in 10% to 30% of invasive carcinoma and behave as poor prognostic markers. ERBB2 abnormalities have also been reported in MBC, yet at lower frequency, but their prognostic significance remains controversial. Furthermore, no study has addressed the impact of chromosome 17 abnormalities in MBC survival. In this study, the ERBB2-gene status (overexpression and amplification) and chromosome 17 numerical abnormalities were investigated in a series of 50 archival cases of MBC. The results, together with patient's age, histologic grade, pathologic stage, and estrogen receptor status were correlated with overall survival. ERBB2-protein overexpression was present in 7 cases (14%), ERBB2-gene amplification in 4 (8%), and aneuploidy of chromosome 17 in 12 cases (33.3%). The pathologic stage, ERBB2 overexpression and ERBB2 amplification were significantly correlated with overall survival (P=0.002, 0.016, and 0.009, respectively). No correlation was observed between chromosome 17 aneuploidy and overall survival. Therefore, despite their low incidence in MBC, expression abnormalities of ERBB2 behave, together with the pathologic stage of the tumor, as predictors of overall survival, akin to what has been reported for its female counterpart.

Adenocarcinoma↗
PubMed2006

DNA flow cytometry but not telomerase activity as predictor of disease-free survival in pT1-2/N0/G2 breast cancer.

OBJECTIVE: In the subgroup of patients with node-negative (N0) moderately differentiated (G2) breast cancer, the clinical decision of giving adjuvant therapy is critical. The aim of this study was to investigate the prognostic value of biomarkers (DNA flow cytometry and telomerase activity in correlation with routinely used estrogen receptors (ER) and HER oncoprotein) in pT1-2/N0/G2 breast cancer, for improving therapeutic management. METHODS: The series involved 135 patients with pT1-2/N0/G2 breast cancer and median follow-up of 58.5 months. DNA ploidy and S-phase fraction (SPF) ( 10%) were assessed on frozen samples. Telomerase activity, ER and c-erbB-2 expression were analyzed by standardized immunohistochemistry techniques. A Cox regression analysis was performed for prognostic evaluation. RESULTS: Aneuploidy significantly correlated with high SPF and lack of ER, while high SPF showed significant correlations with high telomerase activity, c-erbB-2 overexpression and absence of ER. Kaplan-Meier curves showed significant differences for ploidy and SPF in relation with disease-free survival (DFS) and overall survival (OS), and a statistical trend for ER. By Cox regression analysis, DNA aneuploidy (RR = 16.7; p = 0.007) and high SPF (RR = 23.1; p = 0.004) revealed significant correlations with worse DFS. Among patients with diploid (n = 76) and low/intermediate SPF (n = 85) tumors, only one had recurrence of the disease. No association between telomerase activity and clinical outcome was observed. CONCLUSION: In pT1-2/N0/G2 breast cancer patients, DNA ploidy and SPF are relevant prognostic biomarkers that should be considered as additional tools in the therapeutic planning.

Adult↗
PubMed2005

PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry.

Pleomorphic adenoma is the most common benign tumor of the salivary glands. It has marked histological diversity with epithelial, myoepithelial and mesenchymal-type cells arranged in a variety of architectural and differentiation patterns. Pleomorphic adenoma gene 1 (PLAG1), shown to be consistently rearranged in pleomorphic adenomas, is activated by chromosomal translocations involving 8q12, the chromosome region that is most frequently affected in these tumors. In this study, we evaluated PLAG1 involvement in salivary gland tumorigenesis by determining the frequency of its alterations in a selected group of 20 salivary gland tumors: 16 pleomorphic adenomas and four carcinomas ex-pleomorphic adenoma, having in common the presence of karyotypic chromosome 8 deviations, either structural, with 8q12 rearrangements, or numerical, with gain of chromosome 8. PLAG1 status was analyzed using in situ hybridization techniques, on metaphase cells, by fluorescence detection and/or interphase cells in paraffin sections, by chromogenic detection. Except for one pleomorphic adenoma case (5%) that lacked PLAG1 involvement, 17 tumors (85%), (14 pleomorphic adenomas and three carcinomas ex-pleomorphic adenoma) showed intragenic rearrangements of PLAG1 and the remaining two cases (10%), (one pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma), had chromosome trisomy 8 only. To further investigate the role of PLAG1 on pleomorphic adenomas tumorigenesis, as well as the putative morphogenesis mechanism, we attempted to identify the cell types (epithelial vs myoepithelial) carrying 8q12/PLAG1 abnormalities by a combined phenotypic/genotypic analysis in four cases (three pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma) characterized by 8q12 translocations and PLAG1 rearrangement. In these cases, both cells populations carried PLAG1 rearrangements. This finding further supports the pluripotent single-cell theory, which postulates that the tumor-initiated, modified myoepithelial cell, evolves into the varied somatic cell phenotypes present in pleomorphic adenoma, and reinforces the role of PLAG1 on the tumorigenesis of benign and malignant pleomorphic adenoma.

Adenoma, Pleomorphic↗
PubMed2005

Correlations of cell cycle regulators (p53, p21, pRb and mdm2) and c-erbB-2 with biological markers of proliferation and overall survival in breast cancer.

AIM: The biological impact of cell cycle regulatory proteins on breast cancer progression is widely recognised, although mostly unclear. The aim of this preliminary study was to investigate the correlations of several cell cycle modulators (p53, p21, pRb, and mdm2) and c-erbB-2 expression with cell proliferation markers (S-phase fraction [SPF] and Ki-67) and overall survival in breast cancer. METHODS: The series comprised 50 women with stage I-II invasive ductal breast carcinoma (median follow-up 87 months), who were selected for their tumour proliferative characteristics (15 low, 15 high, and 20 intermediate proliferative tumours). Tumour differentiation was assessed following the Nottingham grading criteria. Cell cycle regulators, oestrogen receptor status, and Ki-67 index were analysed by immunohistochemistry on paraffin embedded material (cut-offs 10%). c-erbB-2 was evaluated according to a standardised immunohistochemical assay and borderline cases were confirmed by FISH analysis. Ploidy and SPF were determined by DNA flow cytometry on frozen samples. Chi-square test and Fisher's exact test were applied to analyse the statistical significance of data. RESULTS: Positive immunostaining was observed in nine (18%) p53+, 30 (60%) p21+, 13 (26%) pRb+, and one (2%) mdm2+ cases. c-erbB-2 expression was considered positive in 11 (22%) cases. In the subset of patients dead of the disease, a high incidence of c-erbB-2 over-expression (7/10, 70%) was verified. In general, no significant correlations among cell cycle regulators or between the latter and histopathological or proliferative characteristics were found. Only the p53-/p21+ phenotype significantly correlated with low SPF (p=0.048), and p21 positivity showed a trend to be associated with low SPF (p=0.083). No statistically significant correlations between cell cycle inhibitors and clinical outcome were found. On the contrary, c-erbB-2 over-expression showed significant correlations with DNA aneuploidy (p<0.001), high SPF (p<0.001), high tumour grading (p=0.008), lack of oestrogen receptors (p=0.036), and poor overall survival (p<0.001). CONCLUSIONS: The results seem to indicate the lack of correlations of cell cycle regulatory proteins with cell proliferation markers and overall survival in breast cancer, in contrast to c-erbB-2 over-expression which was found to be associated with increased proliferation rate and worse prognosis.

Adult↗
PubMed2004

A study of MECT1-MAML2 in mucoepidermoid carcinoma and Warthin's tumor of salivary glands.

The t(11;19)(q21;p13) chromosomal translocation has been described in two distinct types of salivary gland neoplasms: mucoepidermoid carcinoma (MEC) and Warthin's tumor (WT). Since this translocation has been recently shown to generate a MECT1-MAML2 fusion gene, we evaluated 10 primary MEC and seven primary WT to further define the molecular association of these two entities using cytogenetic, as well as in situ hybridization (ISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses directed against the fusion gene. A karyotype was established in all neoplasms except for two MEC cases. Of the eight karyotyped MECs, five showed the t(11;19)(q21;p13), two had a normal karyotype, and one case presented a -Y and +X. Three of the WT revealed a normal karyotype and four had several abnormalities which did not involve chromosomes 11 and 19. ISH analysis performed in cytogenetic suspension and/or in tumor paraffin sections demonstrated MAML2 rearrangement in 7 of 10 cases of MEC: all five cases with t(11;19), one case with normal karyotype, and one unkaryotyped case. RT-PCR analysis confirmed the expression of the MECT1-MAML2 gene in all MEC cases that were positive by ISH analysis. Neither the t(11;19) nor MECT1-MAML2 was detected in any case of WT, nor in control samples from polymorphous low-grade adenocarcinoma, acinic cell carcinoma, or normal parotid gland tissue. We have demonstrated that ISH and RT-PCR are sensitive methods for detecting MECT1-MAML2 in MEC. In contrast, we did not detect the t(11;19) nor MECT1-MAML2 expression in seven cases of WT.

Adenolymphoma↗
PubMed2003

Chromosome imbalances in thyroid follicular neoplasms: a comparison between follicular adenomas and carcinomas.

The underlying genetic events associated with follicular thyroid tumorigenesis are still ill defined. In this study, we performed a screening for chromosome imbalances by comparative genomic hybridization (CGH) in a group of 12 follicular adenomas (FAs) and 20 follicular carcinomas (FTCs) previously characterized by conventional cytogenetics and flow cytometry analysis. In general, a great similarity was observed between the CGH profiles of the FAs and FTCs. In both benign and malignant tumors, a combination of gains affecting 5, 7, 12, 17, 19, and 20 was observed. Chromosome 7 was the most frequently affected chromosome, with three regions of consensus gains: 7p11-12, 7q11.3-q21, and 7q31. Recurrent gains of chromosomes 5 and 12 involved 5p11, 5p15, 5q13-q22, 5q21-q23, 12p11, and 12q11-q12. DNA sequence losses were also observed in both tumor groups. Chromosomal arms deleted in at least five of the neoplasms were (in order of frequency): in adenomas, 15q, 2p/2q, 3q, 6p/6q, 11q, and 22q; and in FTCs, 3p, 2p, 8q, 1p, 2q, 3q, 6q, 8p, 9p, 11q, 13q, 6p, and 18q. The statistical evaluation of the CGH data demonstrated that 15q loss was significantly associated with FA. Two regions of minimal common loss were defined by CGH at 15: 15q11-q21 and 15q26-qter. The identification of these regions provides a basis for further molecular studies.

Adenoma↗
PubMed2003

Loss of heterozygosity in follicular and papillary thyroid carcinomas.

In this study we aimed at investigating the incidence and the role of 3p deletions, particularly at the 3p25 approximately pter region, in follicle cell-derived thyroid neoplasms, by using loss of heterozygosity (LOH) analysis. We analyzed 12 follicular adenomas (FA), 13 follicular thyroid carcinomas (FTC), and 15 papillary thyroid carcinomas (PTC) with 11 microsatellite markers for chromosome 3. One additional marker on 3q25.2 was also investigated for assessment of deletion extent on 3q. Microsatellite instability was detected at one locus in 1 of 15 PTC (7%) and at four loci in 1 of 13 FTC (8%). Loss of heterozygosity was found in 8 of 12 cases of FTC (67%), in 6 of 15 cases of PTC (40%), and in 2 of 12 FA (17%). We identified three minimal common deleted regions (CDR) involving significant sites of LOH: two in FTC (a new terminal region, of approximately 8 cM distal to D3S1620 at 3p25.3 approximately pter and the D3S1573-D3S1595 region at 3p21.2 approximately p12) and one in PTC (D3S1304-D3S1263 region at 3p25.3 approximately p24.2). The newly identified 3p25.3 approximately pter CDR seems to be specific for FTC. Our results suggest the existence of at least three distinct regions on 3p that might harbor tumor suppressor genes involved in the carcinogenesis processes of FTC and PTC.

Adenocarcinoma, Follicular↗
PubMed2003

Losses of heterozygosity on chromosomes 9p and 17p are frequent events in Barrett's metaplasia not associated with dysplasia or adenocarcinoma.

OBJECTIVE: Losses of heterozygosity (LOH) on chromosomes 9p and 17p frequently accompany malignant transformation of Barrett's esophagus (BE). They have been reported in adenocarcinoma, dysplasia, and adjacent metaplasia of patients with long-segment BE (LSBE). This study aimed to evaluate and compare the frequency of LOH on 9p and 17p in patients with long- and short-segment BE (SSBE) without dysplasia or adenocarcinoma. METHODS: Matched metaplasia and blood DNA were evaluated for LOH on chromosomes 9p and 17p in patients with a previous diagnosis of BE and no dysplasia or cancer. RESULTS: We included 18 patients (12 long-segment BE and six short-segment BE). The overall prevalence of LOH was 61% (10 of 18), with no significant difference between LSBE (58%) and SSBE (50%). The frequencies of LOH on 9p and 17p were similar (35% and 39%, respectively), with 18% of the patients showing losses at both chromosomes. CONCLUSIONS: LOH on 9p and 17p are highly frequent events in BE, even in the absence of dysplasia and adenocarcinoma. The presence of these abnormalities in non-neoplastic epithelium suggests they might be useful markers for risk stratification within endoscopic surveillance programs.

Adenocarcinoma↗
PubMed2002

Hyalinizing clear cell carcinoma of salivary glands: a study of extracellular matrix.

Hyalinizing clear cell carcinoma (HCCC) is a recently described low-grade carcinoma of the salivary glands presenting two main histological features: clear neoplastic cells and prominent hyalinized stroma. Our aim was to characterize the composition of the hyalinized stroma in three cases of HCCC. An immuno-histochemical study using laminin and type I, III and IV collagens, fibronectin and tenascin antibodies was performed. In one case, electron microscopy study was also done. Collagen I and fibronectin were always present in tumoral stroma. Collagen III was documented in two cases and tenascin at the invasive front of the neoplasm. Collagen IV and laminin were found around neoplastic cells but not at the interstitial stroma. Foci of basal lamina reduplication and large deposits of long space collagen were observed in EM. This study demonstrates that the hyalinized stroma of HCCC is not formed by the accumulation of basement membrane-type material since it is mostly composed by collagen I and fibronectin.

Adenocarcinoma, Clear Cell↗
PubMed2002

Salivary gland-type basal cell adenocarcinoma of presumed bartholin's gland origin: a case report.

Salivary gland-type carcinomas arising in Bartholin's gland are rare neoplasms. We report the case of a 75-year-old female who presented with a vulvar tumor with morphological and immunophenotypical features identical to those of salivary gland basal cell adenocarcinomas. We believe that the tumor was most likely of Bartholin's gland origin, although no Bartholin's gland tissue was found adjacent to the neoplasm. This type of malignancy with myoepithelial differentiation has not been previously reported to arise in the Bartholin's gland.

Adenocarcinoma↗
PubMed2002

High frequency of MALT lymphoma in a series of 14 cases of primary breast lymphoma.

This article reports the clinicopathologic and immunohistochemical findings of 14 cases fulfilling the criteria of Wiseman and Liao for primary lymphoma of the breast (PBL), with emphasis on the frequency of mucosa-associated lymphoid tissue (MALT) lymphomas. The tumors were reclassified according to the revised European-American classification of lymphoid neoplasms. Immunohistochemistry was used to assist in the classification and subtyping of PBL, to demonstrate lymphoepithelial lesions (LEL), and to assess estrogen/progesterone receptor expression. Nine tumors were classified as MALT lymphomas (seven low grade and two high grade), four as diffuse large cell lymphomas and one as follicle center lymphoma. Extensive lymphoid cell infiltration of mammary ducts and acini was also found in non-MALT lymphoma cases. None of the 14 cases expressed hormonal receptors. Primary lymphoma of the breast is a rare and morphologically heterogeneous entity. There is similarity on the clinicopathologic overall profile of the current series of patients and those previously reported, but we recorded a higher incidence of MALT lymphoma (64.3%). Immunohistochemistry is mandatory to identify "true" LEL because epithelial permeation by lymphoid cells can also be found in non MALT-type lymphomas.

Adult↗
PubMed2002

Independent prognostic value of hormone receptor expression and S-phase fraction in advanced breast cancer.

OBJECTIVE: TO assess the prognostic value of immunocytochemically assessed hormone receptor expression and DNA flow cytometry data in advanced breast cancer. STUDY DESIGN: This prospective study with long-term follow-up evaluated the above parameters in relation to overall survival in 392 patients with advanced breast cancer (stages IIB, n = 106; IIIA, n = 66; IIIB, n = 174; and IV, n = 46) using fine needle aspiration cytology. RESULTS: Estrogen and progesterone receptor positivity was detected in 65.1% and 46.1% of the tumors, respectively. DNA aneuploidy was present in 70.9% of the cases, and the median S-phase fraction (SPF) was 9.4%. There was a significant correlation of aneuploidy and high SPF with lack of hormone receptors. The median SPF and SPF tertiles (cutoff values, 6.5% and 12%), applied in the whole series, showed a significant correlation with survival, whereas if SPF was used according to ploidy status, no prognostic significance was found. No differences in relation to survival among different DNA aneuploidy subclasses were verified. In univariate analysis, clinical staging, hormone receptors, DNA ploidy and SPF showed a statistically significant correlation with the overall survival. In multivariate analysis only DNA ploidy did not maintain independent prognostic significance. CONCLUSION: Hormone receptor expression and flow cytometric SPF are independent prognostic factors in advanced breast cancer.

Adult↗
PubMedDate not supplied

[DNA flow cytrometry in solid tumors].

This brief overview outlines the fundamental principles of flow cytometry with emphasis on DNA measurements and cell cycle analysis in human solid tumors. Type of material used, sampling processing procedures and methods of analysis of data are discussed. DNA ploidy and proliferative activity (S-phase fraction) are the two biological parameters commonly measured by DNA flow cytometric analysis. The prime purpose of most studies in this area is the investigation of the prognostic value of DNA flow cytometry in addition to the information provided by conventional clinicopathological factors known to affect disease prognosis. Numerous studies concerning the predictive significance of DNA flow cytometry in some types of solid tumors are reviewed in this article. The general statement, for tumors in the same histopathological stage of the disease, is that diploid and/or low proliferative tumors have a more favourable prognosis than aneuploid and/or high proliferative tumors, suggesting an important role of DNA flow cytometry in the assessment of tumor behaviour and in the outcome evaluation of the disease. However, in some studies this association could not be substantiated, and the prognostic relevance of DNA analysis has been questioned. The potential reasons for conflicting results, namely the methodological pitfalls related to the cell preparation techniques and the histogram interpretation are discussed.

DNA, Neoplasm↗