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Jorge S Reis-Filho

Publications and source records attributed to Jorge S Reis-Filho.

At least 55 records · Page 3Linked to original sources
PubMed2003

P63-driven nuclear accumulation of beta-catenin is not a frequent event in human neoplasms.

deltaN-p63 isoforms may act as oncogenes owing to their ability to bind to p53-reporter genes without inciting their transcription, thus blocking the p53-driven cell cycle arrest and apoptosis. A novel mechanism linking p63 and Wnt pathways has recently been proposed. Briefly, in vitro studies using squamous cell carcinoma cell lines have suggested that deltaN-p63 may block the phosphorylation of beta-catenin, leading to its nuclear accumulation and triggering beta-catenin-responsive transcription of genes related to proliferation and oncogenic biological behavior. To test this new mechanism, the coexpression of deltaN-p63 and beta-catenin was evaluated in a large cohort of human neoplasms. Two serial sections of TARP-4 multi-tumor tissue microarray, composed of 51 normal tissue cores and 400 human neoplasms [breast (n = 75), colon (n = 75), lung (n = 75), prostate (n = 75) and ovary (n = 50) neoplasms, melanoma (n = 25), and glioblastoma (n = 25)] were subjected to immunohistochemistry with deltaN-p63 and beta-catenin monoclonal antibodies. p63 nuclear expression and beta-catenin membranous, cytoplasmic, membranous + cytoplasmic, and nuclear localization were evaluated. deltaN-p63 expression and beta-catenin nuclear localization were found in 92.6% and 0% of squamous cell carcinomas, 8.9% and 0% of breast carcinomas, 13.8% and 0% of lung adenocarcinomas, 1.4% and 23.2% of colon adenocarcinomas, 0% and 4.8% of prostate adenocarcinomas, 11.1% and 5% of ovary carcinomas, 9.0% and 9.1% of malignant melanomas, and 12.5% and 40.0% of glioblastomas, respectively. No statistically significant association between deltaN-p63 and nuclear beta-catenin expression was found for all tumors. At variance with squamous cell carcinoma cell lines, p63-driven nuclear accumulation of beta-catenin is an unusual phenomenon in human neoplasms. Caution should be exercised when translating the results of studies performed on cell lines to human neoplasms.

Cell Nucleus↗
PubMed2003

Novel and classic myoepithelial/stem cell markers in metaplastic carcinomas of the breast.

Metaplastic carcinomas of the breast (MCBs) are unusual neoplasms characterized by an admixture of glandular epithelial components, which frequently exhibit features of squamous differentiation, and mesenchymal malignant components. Regardless of the presence of myoepithelial features in MCB, no consensus concerning their putative histogenesis has yet been achieved. Recently, novel putative myoepithelial markers have been developed, including p63, maspin, and P-cadherin. We assessed the expression of these myoepithelial markers in MCBs and compared their expression with classic myoepithelial markers. Immunohistochemistry using the streptavidin-biotin-peroxidase complex technique with antibodies raised against p63, maspin, P-cadherin, actin (clones CGA7, 1A4 and HHF35), cytokeratin 14 (Ck14), and vimentin was performed on 16 MCBs (7 matrix-producing MCBs, 6 adenosquamous MCBs, and 3 MCBs with heterologous elements). In healthy breast lobules and ducts adjacent to the tumors, myoepithelial cells showed distinctive and consistent immunoreactivity for p63, maspin, P-cadherin, actin, S-100 protein, and Ck14. Matrix-producing MCBs were positive for maspin in all cases, for p63 in 4 of 7 cases, and for P-cadherin in 4 of 7 cases. Adenosquamous MCB showed immunoreactivity for p63, maspin, and P-cadherin in 5 of 6 cases. All novel myoepithelial markers and Ck14 decorated squamous cell islands. MCBs with heterologous elements were positive for p63 in 1 case, for maspin in all 3 cases, and for P-cadherin in 2 cases. All cases showed at least one of the novel myoepithelial markers. Eleven of 16 cases were positive for actin. Eleven of 14 cases reacted with Ck14, and all cases that stained for S-100 protein (9 of 9) and vimentin (13 of 13) were also positive. Based on our findings, the balance of probabilities favors that MCBs may have a basal or myoepithelial cell histogenesis and differentiation.

Actins↗
PubMed2003

p63 expression in solid cell nests of the thyroid: further evidence for a stem cell origin.

Solid cell nests of the thyroid are embryonic remnants of endodermal origin that may be difficult to distinguish from squamous metaplasia, metastatic squamous carcinoma, papillary microcarcinoma, medullary carcinoma, and C-cell hyperplasia. These embryonic structures are composed of main cells and C-cells; cystic structures and mixed follicles are sometimes observed intermingled with solid cell nests. Recently, p63, a p53 homologue that is consistently expressed in basal/stem cells of stratified epithelia and plays a major role in triggering the differentiation of some specific cell lineages, has been characterized. We evaluated the immunohistochemical expression of p63, cytokeratins (CAM 5.2, AE1/AE3, 34betaE12, 7, and 20), carcinoembryonic antigen, thyroid transcription factor 1 (TTF-1), thyroglobulin, and calcitonin using the streptavidin-biotin-peroxidase complex technique in 6 bona fide solid cell nests. We observed that main cells of solid cell nests are strongly decorated by p63, while C-cells and all other thyroid structures were consistently negative. Moreover, main cells expressed carcinoembryonic antigen and all cytokeratins but cytokeratin 20 and lacked TTF-1, thyroglobulin and calcitonin. In contrast to this, C-cells of solid cell nests were immunoreactive for calcitonin, CAM 5.2, AE1/AE3, and cytokeratin 7; focal immunoreactivity for TTF-1 was also observed in some C-cells. We conclude that main cells of the solid cell nests display a basal/stem cell phenotype (p63 and basal cytokeratin positivity), whereas C-cells show features of parafollicular differentiation. We conclude, furthermore, that p63 antibodies may help in distinguishing solid cell nests from their mimics.

Adenoma↗
PubMed2003

Expression of c-met tyrosine kinase receptor is biologically and prognostically relevant for primary cutaneous malignant melanomas.

OBJECTIVES: The c-met tyrosine-kinase receptor and its ligand hepatocyte growth factor are involved in cell survival, proliferation, motility, and invasion. Experimental data have suggested a putative role in melanomagenesis and progression of cutaneous malignant melanoma (CMM). We sought to evaluate c-met expression in a cohort of 62 primary CMM patients diagnosed and primarily treated at the same institution. METHODS: Sixty-two cases of CMM were retrospectively retrieved from the archives of the Department of Pathology, Hospital São João, Porto, Portugal. All classical clinicopathological features were reviewed. Only those patients in whom representative paraffin blocks were available and the diagnosis of primary CMM was confirmed, and who were followed up after the primary diagnosis were included in the study. Immunohistochemistry for c-met was performed in 59 cases, and semiquantitatively and qualitatively (membranous and cytoplasmic, M+C, or cytoplasmic) evaluated. Statistical analysis was performed using chi(2), ANOVA and Kaplan-Meier/log-rank tests. RESULTS: M+C pattern of c-met expression was significantly associated with presence of vertical growth phase (p = 0.0198), thick tumors (p = 0.0006), ulceration (p = 0.0386), high mitotic index (p = 0.0008), lymphatic (p = 0.0086) and vascular (p = 0.0080) invasion, and nodal (p = 0.0422) and combined (nodal and/or visceral) metastases (p = 0.0234). M+C pattern of c-met expression also proved to be a significant prognostic factor for overall survival in univariate analysis (p = 0.0125). CONCLUSIONS: Our findings suggest that the pattern of c-met expression is a relevant prognostic factor for overall survival and is associated with more aggressive behavior of primary CMMs.

Adolescent↗
PubMed2002

Maspin expression in normal skin and usual cutaneous carcinomas.

Maspin is a serine protease inhibitor whose gene is located on 3q27. Several lines of evidence point towards its putative role as tumor suppressor gene and angiogenesis inhibitor; however, there are compelling data showing that maspin is also expressed in the nuclear compartment and might be associated with the differentiation of specific cell lineages. No systematic study of maspin expression in normal skin and usual skin carcinomas have been published so far. We semiquantitatively analyzed the distribution and immunoreactivity pattern of maspin in 14 squamous cell carcinomas (SCCs) and 16 basal cell carcinomas (BCCs) and in the adjacent normal epidermis of all cases. We also examined the correlation of maspin expression with histological type, grade, vascular invasion, perineural infiltration, and mitotic counting. Cytoplasmic expression of maspin was observed in suprabasal, prickle, and granular cell layers of normal epidermis; cells of the germinative hair matrix, Henle's and Huxley's layers, and cuticle of hair follicles; mature sebaceous cells and sweat gland's secretory cells. Nuclear expression was detected in some basal/myoepithelial cells of the sweat glands and scattered mature sebaceous cells. All SCCs but one grade IV SCC showed maspin expression, and it was correlated with the differentiation of these neoplasms. BCCs presented variable maspin expression, while metatypical carcinomas showed moderate to intense maspin expression, nodular BCCs variable contents of maspin and displayed a peculiar distribution, confined to the center of the neoplastic nodules. Two BCCs and one SCC showed maspin nuclear expression. No correlation with other clinical pathological features was observed. Our findings do not support the role of maspin as a tumor suppressor gene and suggest that this serpin is probably associated with specific lines of differentiation.

Adult↗
PubMed2002

Primary epithelial malignant mesothelioma of the pericardium with deciduoid features: cytohistologic and immunohistochemical study.

Malignant mesothelioma with deciduoid features (MMWDF) is a recently characterized morphologic variant of epithelioid malignant mesothelioma, which frequently is misdiagnosed as peritoneal deciduosis or florid mesothelial hyperplasia. We report on the cytological, histological, immunohistochemical, and autopsy findings of a case of MMWDF arising in the pericardium of a 71-yr-old female patient. Cytology showed large, polygonal to round cells with pale to bright, eosinophilic cytoplasm, occasionally showing xantomatous pattern, containing a pleomorphic and vesicular nucleus with a single prominent nucleolus. Autopsy examination showed a neoplasm encasing the heart and great vessels. No other primary neoplasm was found. The histological analysis disclosed the typical features of MMWDF. Immunohistochemistry showed diffuse immunoreactivity for cytokeratin MNF116, HBME-1, and calretinin in the neoplastic cells, as well as focal positivity for epithelial membrane antigen positivity in a brush border-like pattern. All other markers were negative. We would like to stress that pathologists must be aware of the cytological and histological features of this rare variant of epithelioid malignant mesothelioma in order to avoid a misdiagnosis of a benign process or a metastatic malignancy.

Aged↗
PubMed2002

Naked nuclei revisited: p63 Immunoexpression.

The presence of naked nuclei (NN) in cytological preparations of fibroadenomas is a well-known finding. Regardless of their importance on the differential diagnosis of fibroadenoma and other benign lesions of the breast, the origin of NN remains elusive. Despite previous efforts to characterize them, the lack of a reliable nuclear marker for myoepithelial cells impaired definitive conclusions. We performed a systematic evaluation of p63 expression in cytological and histological preparations of 10 fibroadenoma specimens. We observed that in histological sections, p63 was restricted to the nuclei of myoepithelial/basal cells in lobules and ducts of normal breast. In fibroadenomas, p63 decorated the nuclei of myoepithelial cells in the periphery of epithelial duct-like formations and slit-like formations. No p63 immunoreactivity was observed in stromal or epithelial cells. In cytological samples, almost all NN and cells surrounding epithelial cell clusters were stained; no stromal cell admixed with fibrillary matrix or epithelial cell was stained with p63. Based on our findings, we strongly suggest that most, if not all, NN are myoepithelial in origin.

Breast↗
PubMed2002

Eosinophilic angiocentric fibrosis of the sinonasal tract: report on the clinicopathologic features of a case and review of the literature.

BACKGROUND: Eosinophilic angiocentric fibrosis (EAF) is a rare fibroinflammatory lesion of the sinonasal tract that occurs mainly in young to middle-aged female patients. Only two previous cases affecting male patients have been reported, and its etiopathogenesis remains unknown. The authors report on the third case of the entity in a male patient and review the 12 previously reported cases. CASE REPORT: A 52-year-old male patient was initially seen with a 15 years history of allergic rhinitis, progressive nasal obstruction, and left-sided hearing loss. All laboratory tests were unremarkable, except the nasal discharge eosinophil count that showed a conspicuous eosinophilia. The video-assisted-nasofibroscopic examination and CT scans disclosed a thickened deviated nasal septum with a subjacent infiltrative lesion. The histologic analysis of the nasal septum showed a variable mixed inflammatory cellular infiltration mainly composed of eosinophils, plasma cells, and histiocytes with a perivascular distribution; in other areas, an angiocentric fibrosing lesion with a peculiar perivascular onion-skin pattern was observed. The patient had a partial resection of the lesion with symptomatic control. CONCLUSIONS: The presence of rhinitis and nasal eosinophilia in our case associated with the clinical aspects of the previously reported cases further support an allergic cause for EAF.

Eosinophils↗