Biomedical subjects

D Leitão

Publications and source records attributed to D Leitão.

8 recordsLinked to original sources

PubMed2004

Clinicopathological significance and survival influence of p53 protein expression in gastric carcinoma.

AIMS: Mutations in the gene coding for p53 protein are among the most frequent genetic alterations observed in human cancers. The relevance and biological significance of p53 expression in gastric carcinoma are far from being fully established. The aim of our study was to evaluate the influence of p53 detected by immunohistochemistry in the clinicopathological behaviour of a series of gastric carcinoma cases. METHODS AND RESULTS: Samples from 163 patients treated by gastric resection for gastric carcinoma between 1988 and 1995 were used. Surgical specimens were evaluated for the presence of p53 protein detected by immunohistochemistry with a monoclonal antibody. Cases were classified as positive or negative for p53. Several clinicopathological parameters and c-erb B-2 expression were analysed in the same series and compared with the expression of p53. Cumulative survival was evaluated using univariate analysis and Cox model regression. p53 expression was identified in 41 carcinomas (25.2%) and was significantly associated with venous invasion (P = 0.049), lymph node metastases (P = 0.01) and c-erb B-2 expression (P = 0.003). All the parameters except gender, tumour size and Laurén's classification influenced survival on univariate analysis. p53 expression correlated with overall survival (P = 0.006) and survival in the subgroup of patients with intestinal type carcinoma (P = 0.04). In the subgroup of patients with carcinomas not expressing c-erb B-2, p53 expression significantly influenced cumulative survival (P = 0.02). CONCLUSIONS: p53 expression is associated with the aggressive biological behaviour of gastric carcinomas and is related to cumulative survival.

Adult↗

PubMed2004

c-KIT and PDGFRA in breast phyllodes tumours: overexpression without mutations?

AIM: To study the immunoexpression and mutational status of c-KIT and PDGFRA in a series of benign and malignant phyllodes tumours of the breast. MATERIAL/METHODS: Nineteen phyllodes tumours (13 benign and six malignant) were analysed by immunohistochemistry for the expression of c-KIT and PDGFRA. Direct sequencing of exons 9, 11, 13, and 17 of the c-KIT gene and exons 12 and 18 of PDGFRA was performed to check the mutational status of these two genes. RESULTS: c-KIT expression was found in 12 of the 19 cases (six of the 13 benign cases and all six malignant ones) and PDGFRA expression was seen in two of the 19 cases (one benign and one malignant case); the 2415 C>T alteration in exon 17 of the c-KIT gene was found in two cases (both benign); the intronic insertion IVS17-50insT and the 2866 G>T alteration in the coding region of exon 18 of the PDGFRA gene were also found in two cases (one malignant and one benign). However, the activating mutations described for these genes in gastrointestinal stromal tumours were not present. CONCLUSION: c-KIT expression is a frequent finding in phyllodes tumours, particularly in malignant cases; however, no activating mutations similar to those described for gastrointestinal stromal tumours were found. The PDGFRA does not seem to be an alternative pathway to tumour development in phyllodes tumours because neither expression nor activating mutations were noteworthy.

Biomarkers, Tumor↗

PubMed2002

Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer.

AIMS: Cyclo-oxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis. COX-2 is induced by a wide variety of stimuli, and present during inflammation. COX-2 overexpression has been observed in colon, head and neck, lung, prostate, stomach, and breast cancer. In colon and gastric cancer, COX-2 expression was associated with angiogenesis. The aim of this study was to determine the relation between COX-2 expression and angiogenesis in breast cancer, and to correlate the expression of this enzyme with classic clinicopathological parameters. METHODS: COX-2 expression was investigated by immunohistochemistry and western blotting analysis. The expression of COX-2 was then related to age, histological grade, nodal status, oestrogen receptor status, p53 expression,c-erb-B2 overexpression, mitotic counts, MIB-1 labelling index, apoptotic index, sialyl-Tn expression, transforming growth factor alpha expression, microvessel density, and disease free survival in 46 patients with invasive ductal breast carcinoma. RESULTS: By means of immunohistochemistry, COX-2 expression was detected in eight of the 46 carcinomas studied. Western blotting showed COX-2 protein expression in the same breast tumours, but not in normal adjacent tissues. The density of microvessels immunostained with anti-F-VIII related antigen was significantly higher in patients with COX-2 expression than in those without expression (p = 0.03). In addition, COX-2 was significantly associated with the presence of sialyl-Tn expression (p = 0.02), lymph node metastasis (p = 0.03), a high apoptotic index (p = 0.03), and a short disease free survival (p = 0.03) in univariate analyses. CONCLUSIONS: These data suggest that COX-2 expression is associated with angiogenesis, lymph node metastasis, and apoptosis in human breast cancer. Moreover, these results warrant further studies with larger series of patients to confirm the association with short disease free survival in patients with breast cancer.

Adult↗

PubMed2001

CD99/MIC-2 surface protein expression in breast carcinomas.

AIM: To evaluate the expression of CD99/MIC-2 surface protein in invasive breast carcinomas and demonstrate whether or not there is a relationship with tumour phenotype. METHODS AND RESULTS: Thirty-five invasive breast carcinomas, including five metaplastic carcinomas, were stained with CD99 primary antibodies using standard protocols based on streptavidin-biotin-peroxidase method. Four out of five metaplastic carcinomas expressed CD99/MIC-2 protein, three of them were matrix-producing carcinomas. From the other 30 cases, only an invasive apocrine carcinoma was positive. There was no statistical correlation between CD99 expression and the parameters analysed (histological typing and grading, proliferative index and nodal status). CONCLUSIONS: CD99/MIC-2 is expressed in breast carcinomas, especially in the matrix-producing variant of metaplastic carcinomas, which impairs its use as a marker to differentiate metaplastic carcinomas from primary and metastatic sarcomas of the breast. It seems to have no prognostic implications. However, phenotype similarities with other chondromyxoid tumours that also express the protein, like mesenchymal chondrosarcomas, suggest a relationship between MIC-2 reactivity and morphological differentiation.

12E7 Antigen↗

PubMed2000

Is TTF1 a good immunohistochemical marker to distinguish primary from metastatic lung adenocarcinomas?

To evaluate the immunohistochemical expression of thyroid transcription factor 1 (TTF1) in primary and metastatic pulmonary adenocarcinomas, and test the diagnostic accuracy of this antibody, two surgical pathologists independently evaluated 34 cases of adenocarcinomas in the lung without clinical data and tried to distinguish between primary and metastatic cases using histological criteria exclusively. Thirteen cases were primary in the lung and 21 were metastases of extrapulmonary adenocarcinomas: 6 from the endometrium, 4 from the ovary, 3 from the colon, 2 from the kidney, 2 from the breast, 2 from the liver and 1 from the prostate. Afterward, the immunoreactivity of TTF1 in these neoplasms was evaluated and correlated with morphological and clinical data. The two pathologists were able to diagnose only 5 out of 13 cases of primary lung adenocarcinomas (sensitivity of 38.46%) and also misdiagnosed two primary malignancies as metastases. After correlation with TTF1 data, the sensitivity increased to 61.53%. The specificity of TTF1 was 100%. In conclusion, TTF1 is a highly specific marker for primary lung adenocarcinomas, and should be included in a panel of antibodies for the differential diagnosis between primary and metastatic adenocarcinomas of the lung.

Adenocarcinoma↗

PubMed1998

Detection of numerical chromosome 17 abnormalities in fine-needle aspirates of breast cancer using a novel in situ hybridization signal amplification method.

We describe a method of in situ hybridization (ISH) to assess numerical chromosome abnormalities on alcohol-fixed smears obtained by fine-needle aspiration from breast cancer patients, using a commercially available amplification kit to demonstrate numerical chromosome alterations of chromosome 17. In this staining procedure after detection of the biotin-labeled alpha-satellite probe for chromosome 17 with avidin-biotin-peroxidase, we incorporated a signal amplification based on the peroxidase-catalyzed deposition of a biotinylated phenolic compound followed by a secondary reaction with peroxidase. The reactions are revealed by deposition of diaminobenzidine and can be analyzed in an optical microscope, with total preservation of the morphology, allowing a direct morphologic-cytogenetic correlation. A series of 25 cases of aspirates from breast cancer were analyzed with this methodology. Aneusomy was found in 14 cases (56%), whereas 11 (44%) had a normal number of chromosome 17 copies. Polysomy occurred in all aneusome cases except one. We did not find concordance between numerical chromosome abnormalities of chromosome 17 and nuclear grading as well as with the immunoexpression of p53 and c-erbB2 studied in the smears. We conclude that the application of the ISH signal amplification method on alcohol-fixed smears will eliminate the need for fresh material and will provide several advantages, such as improvement of morphological concomitant analysis without the need for a fluorescence microscope; utilization, whenever malignancy is found, without necessity to reaspirate the patient; and adequacy of archival material.

Adult↗

PubMed1997

Ki67 labelling index in gastric carcinomas. An immunohistochemical study using double staining for the evaluation of the proliferative activity of diffuse-type carcinomas.

The aim of the present study was to clarify the conflicting recorded data on the proliferative features of gastric carcinoma. The Ki67 labelling index (Ki67 LI) was evaluated using MIB-1 in 43 carcinomas (24 diffuse and 19 intestinal). In 18 cases, differential counts were performed in superficial and deep layers. In ten diffuse carcinomas with a prominent desmoplastic response, Ki67 LI was evaluated in sections double-stained with MIB-1 and CAM5.2. Flow cytometry was performed in 26 cases. Ki67 LI of diffuse carcinomas (36.3 +/- 19.0) was not significantly different from that of intestinal carcinomas (28.2 +/- 18.5). Ki67 LI was significantly higher (P = 0.006) in superficial than in deep areas (41.9 +/- 22.7 and 29.7 +/- 19.7, respectively) regardless of histological tumour type. No significant relationship was observed between Ki67 LI and wall invasion, lymph node metastasis, vascular invasion or ploidy. The following conclusions were drawn: double immunostaining techniques are apparently the best way to overcome the underestimation of cell proliferation in diffuse gastric carcinomas with a prominent desmoplastic response; the diffuse and intestinal types of gastric carcinoma have proliferation rates within the same range, even when the comparison is restricted to diploid tumours; and, finally, the major pool of proliferating cells resides in the superficial areas of gastric carcinomas, regardless of the histotype, which should be taken into consideration when overall counts are performed, using either immunohistochemical markers in tissue sections or suspensions of nuclei in flow cytometry.

Adenocarcinoma↗

PubMedDate not supplied

DNA quantification and ploidy patterns in human adrenocortical neoplasms.

The determination of DNA ploidy and the study of the cell cycle in adrenocortical tumoral cells could help in the distinction between benign and malignant lesions and also in the prediction of the biological behaviour of these tumors. We analysed 32 cases of adrenal tissue (8 normal adrenals--N, 12 benign adenomas--A and 12 carcinomas--C). DNA was quantified by image analysis of Feulgen stained sections (Ahrens System) employing ACAS3 software. The DNA content was considered to be diploid in 70% of the N and in 67% of the A groups and in none of C. In this latter group nearly 90% were triploid or tetraploid while this did not occur in any of the A cases. The percentage of cases with a 5c-exceeding rate (5cER) above 5% was nil in the N and A groups and 100% in C. In what concerns the distribution in the cell cycle we found a very distinctive pattern between the groups as the percentage of cases in which the S-phase fraction exceeded 33% was nil in the normals, 8% in A and 83% in the C cases. In conclusion, there was a good correlation between the analysed parameters and the clinically defined groups of adrenal cortex tumors.

Adenoma↗