Imunomarcação de proteínas de estresse (HSP 27, HSP 72, HSP 90) e proteína P53 em neoplasias mamárias de cadelas

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects

Queilite actínica é a principal lesão pré-neoplásica do lábio. O carcinoma espinocelular do lábio é incluído nas estatísticas brasileiras junto com os cânceres de boca e, em conjunto, somam 40% dos cânceres de cabeça e pescoço. Há certo desconhecimento médico e odontológico em geral quanto aos fatores relacionados à carcinogênese e à progressão de tumores de boca. Genes de supressão tumoral e proteínas regulatórias de proliferação celular exercem papel na evolução da queilite actínica para carcinoma espinocelular e no comportamento biológico deste. O conhecimento de marcadores de diagnóstico e prognóstico e sua investigação têm utilidade no acompanhamento de tais pacientes.

Gene Mutations and Polymorphisms of TP53 and FHIT in Chronic Esophagitis and Esophageal Carcinoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Aneuploidies, deletion, and overexpression of TP53 gene in intestinal metaplasia of patients without gastric cancer

Gastric carcinogenesis is attributable to interacting environmental and genetic factors, through a sequence of events including intestinal metaplasia. Using a fluorescence in situ hybridization technique, we investigated the occurrence of ancuploidies of chromosomes 3, 7, 8, 9, and 17, TP53 gene deletion, and expression of p53 in 21 intestinal metaplasia (IM) samples from cancer-free patients and in 20 gastric adenocarcinoma samples. Aneuploidies were found in 71% (15/21) of the IM samples. Trisomy of chromosomes 7 and 9 occurred mainly in complete-type IM; in the incomplete type, trisomy of chromosomes 7 and 8 were more commonly found. The TP53 gene deletion was observed in 60% (3/5) of the IM cases, and immunohistochemistry revealed p53 overexpression in 12% (2/17) of the analyzed IM cases. All gastric adenocarcinoma cases presented higher frequencies of trisomy or tetrasomy of chromosomes 3, 7, 8, 9, and 17. The TP53 deletion was found in all three of the gastric adenocarcinoma analyzed for it, and immunohistochemistry detected overexpression of protein p53 in 80% (12/15) of the analyzed cases. Our study revealed for the first time the presence of aneuploidies of chromosomes 7, 8, 9, and 17 and of TP53 gene deletion and overexpression in IM samples from cancer-free patients. These results suggest that IM and gastric adenocarcinoma may share the same genetic alterations. (C) 2004 Elsevier B.V. All rights reserved.

Apoptose em otorrinolaringologia e cabeça e pescoço

This paper intend to review recent advances in our understanding of programmed cell death, or apoptosis, and discuss implications of these basic science advances in the development of causes and potential treatments of a variety of diseases of the head and neck. Conclusions: apoptosis is now understood to be important in the normal development and survival of all multicellular organism. Deregulation of this normally tighly controlled process underlies a variety of disease states, including neoplasia, autoimmune disease, and disorders of the central nervous system. A better understanding of this process and regulation may help otolaryngologists better understand diseases relevant to this specialty and will lead to improved therapeutic interventions.

Blepharocheilodontic (BCD) syndrome: Expanding the phenotype?

We describe affected individuals in three generations of a family and another sporadic case, all Brazilian patients, with a combination of signs that diagnose the BCD syndrome. In addition to the cardinal signs, the sporadic case has hypothyroidism and imperforate anus, which was observed previously in one patient. The broadened phenotype and the possibility of involvement of p63 and IRF6 genes in this condition are discussed. © 2003 Wiley-Liss, Inc.

Genetic alterations in benign lesions: Chronic gastritis and gastric ulcer

Aim: To investigate the occurrence of chromosome 3, 7, 8, 9, and 17 aneuploidies, TP53 gene deletion and p53 protein expression in chronic gastritis, atrophic gastritis and gastric ulcer, and their association with H pylori infection. Methods: Gastric biopsies from normal mucosa (NM, n = 10), chronic gastritis (CG, n = 38), atrophic gastritis (CAG, n = 13) and gastric ulcer (GU, n = 21) were studied using fluorescence in situ hybridization (FISH) and immunohistochemical assay. A modified Giemsa staining technique and PCR were used to detect H pylori. An association of the gastric pathologies and aneuploidies with H pylori infection was assessed. Results: Aneuploidies were increasingly found from CG (21%) to CAG (31%) and to GU (62%), involving mainly monosomy and trisomy 7, trisomies 7 and 8, and trisomies 7, 8 and 17, respectively. A significant association was found between H pylori infection and aneuploidies in CAG (P = 0.0143) and GU (P = 0.0498). No TP53 deletion was found in these gastric lesions, but p53-positive immunoreactivity was detected in 45% (5/11) and 12% (2/17) of CG and GU cases, respectively. However, there was no significant association between p53 expression and H pylori infection. Conclusion: The occurrence of aneuploidies in benign lesions evidences chromosomal instability in early stages of gastric carcinogenesis associated with H pylori infection, which may confer proliferative advantage. The increase of p53 protein expression in CG and GU may be due to overproduction of the wild-type protein related to an inflammatory response in mucosa. © 2006 The WJG Press. All rights reserved.

A randomized and controlled trial about the use of oral isotretinoin for photoaging

Topical retinoids are used to treat photoaging; oral isotretinoin is gold standard for acne; off label indications, including photoaging, have been reported with insufficient evidence of efficacy. This is a randomized controlled phase II trial with clinical and histological assessment to evaluate efficacy and safety of oral isotretinoin for photoaging. Study population was comprised of 32 menopausal or sterilized women, aged 40-55, divided in 2 groups: A (21) received 20mg isotretinoin, 3 times per week, nightly moisturizer, and daily sunscreen, for three months; B (11) just moisturizer/sunscreen. Main outcome measures were: overall clinical assessment; profilometry, corneometer and elasticity tests in periocular regions and left forearm; before/after biopsies from left forearm in patients of B and in 10 randomly selected of A. Microscopic blinded evaluation of epidermal thickness, dermal elastosis, new collagen, p53 epidermal expression was performed by quantitative digital image analysis. All data were submitted to statistical analysis. Clinical evaluation showed slight improvement; profilometry, corneometer and skin elasticity tests presented significant difference in pre/post values (P = 0.001 to 0.028), but no differences between A/B. Histological findings and p53 expression were comparable between groups before treatment (P > 0.1); microscopic analysis showed no differences between groups for most variables, after treatment. Slight but significant difference between A/B for p53 with major reduction post isotretinoin [0.66±0.31 vs. 0.94±0.34 respectively (P = 0.04) was observed. There were minor side effects and no significant laboratory test alterations. We concluded that no significant clinical, microscopic changes but p53 epidermal expression reduction were observed. The role of ultra-violet induced p53 mutation in skin carcinogenesis reinforces retinoids chemoprevention. Oral isotretinoin seemed safe but not effective to treat photoaging. Caution should be considered for women prone to pregnancy. Further controlled studies are necessary. © 2010 The International Society of Dermatology.

Chromosomal imbalances in successive moments of human bladder urothelial carcinoma

Objective: To understand developmental characteristics of urinary bladder carcinomas (UBC) by evaluating genomic alterations and p53 protein expression in primary tumors, their recurrences, and in the morphologically normal urothelium of UBC patients. Methods: Tumors and their respective recurrences, six low-grade and five high-grade cases, provided 19 samples that were submitted to laser microdissection capture followed by high resolution comparative genomic hybridization (HR-CGH). HR-CGH profiles went through two different analyses-all tumors combined or classified according to their respective histologic grades. In a supplementary analysis, 124 primary urothelial tumors, their recurrences, and normal urothelium biopsied during the period between tumor surgical resection and recurrence, were submitted to immunohistochemical analyses of the p53 protein. During the follow-up of at least 21 patients, urinary bladder washes citologically negative for neoplastic cells were submitted to fluorescence in situ hybridization (FISH) to detect copy number alterations in centromeres 7, 17, and 9p21 region. Results and Conclusions: HR-CGH indicated high frequencies (80%) of gains in 11p12 and losses in 16p12, in line with suggestions that these chromosome regions contain genes critical for urinary bladder carcinogenesis. Within a same patient, tumors and their respective recurrences showed common genomic losses and gains, which implies that the genomic profile acquired by primary tumors was relatively stable. There were exclusive genomic alterations in low and in high grade tumors. Genes mapped in these regions should be investigated on their involvement in the urinary bladder carcinogenesis. Successive tumors from same patient did not present similar levels of protein p53 expression; however, when cases were grouped according to tumor histologic grades, p53 expression was directly proportional to tumor grades. Biopsies taken during the follow-up of patients with history of previously resected UBC revealed that 5/15 patients with no histologic alterations had more than 25% of urothelial cells expressing the p53 protein, suggesting that the apparently normal urothelium was genomically unstable. No numerical alterations of the chromosomes 7, 17, and 9p21 region were found by FISH during the periods free-of-neoplasia. Our data are informative for further studies to better understand urinary bladder urothelial carcinogenesis. © 2013 Elsevier Inc.

Lesão de células gigantes periférica da cavidade bucal: avaliação da agressividade das lesões por meio dos estudos clínico-radiográfico retrospectivo, histopatológico, histoquímico e imunohistoquímico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prognóstico em osteossarcoma: análise clínica, epidemiológica, histopatológica e imuno-histoquímica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Respiratory immunohistochemical study in rats exposed to cigarette smoke and alcohol

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Apoptose no carcinoma de próstata

Pós-graduação em Patologia - FMB

Reactivity of p53 protein in canine transmissible venereal tumor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)