Cell-cycle analysis and apoptosis-associated proteins in cervical lesions of Brazilian women.

AIM: The aim of the present study was to detect the relative expressions of p53, p21(Waf1/Cip1), p27(Kip1) Bcl-2 and cleaved caspase-3 in cervical lesion samples from Brazilian women by immunohistochemistry. MATERIALS AND METHODS: A total of 230 cervical biopsies in paraffin-embedded blocks were studied: 43 were invasive squamous cell carcinomas (SCC), 52 carcinomas in situ/cervical intraepithelial neoplasias III (CIN III), 54 cervical intraepithelial neoplasias II (CIN II), 51 cervical intraepithelial neoplasias I (CIN I) and 30 non-neoplastic lesions (NN) with benign cellular changes. RESULTS: Significant differences were observed in the p53 expression between the different groups: NN and CIN I (p=0.010); NN and CIN II (p<0.00001); CIN II and CIN III (p=0.02); CIN II and CIS (p=0.0220); CIN II and CEC (p=0.010). Regarding p21(WAF1/Cip1), significant differences were observed between NN and CEC (p=0.001); CIN I and CEC (p=0.001); CIN II and CIN III (p=0,001); CIN II and CIS (p=0.0004) and CIN II and CEC (p<0.0001). For p27(Kip1), significant differences were observed between NN and CIN I (p<0.00001); NN and CIN II (p<0.00001); NN and CIS (p=0.038); CIN I and CIN III (p=0.001); CIN I and CIS (p=0.009); CIN I and CEC (p=0.0001); CIN II and CIN III (p=0.0003); CIN II and CIS (p=0.002); CIN II and CEC (p< 0.00001). Bcl-2 and caspase-3 did not show remarkable differences between groups. CONCLUSION: p53, p21(WAF1/CIP1), p27(KIP1) appear to be involved in the course of carcinogenesis. Rare expression of Bcl-2 and cleaved caspase-3 suggests that these proteins probably do not participate in cervical apoptosis.

HSP27 is commonly expressed in cervical intraepithelial lesions of Brazilian women.

Heat shock proteins are molecular chaperones that may be constitutively present in cells protecting them from various stresses, such as extreme temperature, anoxia or chemical agents. Cervical cancer is the second most prevalent malignancy of women. In this study, we analyzed the expression of Hsp27 by immunohistochemistry in cervical intraepithelial lesions of Brazilian women, along with samples from non neoplasic lesions (NN). Cervical intraepithelial neoplasia I (CIN I), II (CIN II) and III (CIN III)/in situ carcinoma and squamous cell carcinoma (SCC) were included. Immunostaining was observed in 30 (100%) samples of NN, 46 (92%) in CIN I, 50 (100%) in CIN II, 52 (98.11%) in CIN III/CIS, and 46 (98.11%) in SCC. In group NN Hsp27 immunostaining was heterogeneous, more intense in basal and parabasal layers of the epithelium and less or absent in the intermediate and superficial layer. The majority of the samples of CIS and SCC presented strong staining in allepithelial layers. Metaplasic cells, when present, were strongly stained. In this study, Hsp27 protein was found to be commonly expressed in cervical epithelial cells.

Linfadenite necrotizante nistiocítica / Histiocytic necrotizing lymphadenitis

A doença de Kikuchi-Fujimoto é uma desordem de condição clínico-patológica benigna e autolimitada, que afeta predominantemente mulheres jovens. Acomete preferencialmente a cadeia linfonodal cervical e comumente está associada a sintomas inespecíficos, como febre e artralgia. Este trabalho tem por objetivo relatar e evidenciar a associação entre as patologias lúpus eritematoso sistêmico e doença de Kikuchi-Fujimoto, através do caso de paciente do sexo feminino, branca, 16 anos de idade, com quadro de linfadenopatia cervical, febre e artralgia e cujo anatomopatológico de biópsia linfonodo cervical evidenciou linfadenite necresante histiocítica. As provas imunológicas foram positivas para lúpus eritematoso sistêmicos e houve resposta ao tratamento com corticosteróides.

Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients.

INTRODUCTION: Systemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients. METHODS: We studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group). RESULTS: In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019). CONCLUSION: We conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment.

Peripheral blood c-erbB-2 expression by reverse transcriptase-polymerase chain reaction in breast cancer patients receiving chemotherapy.

Minimal residual disease (MRD) evaluation in breast cancer patients is a promising tool to improve current staging procedures. In a previous work employing a CK-19-based reverse transcriptase-polymerase chain reaction (RT-PCR) technique for MRD detection, we identified a group of women who exhibited persistent negativity for this assay and for whom this technique was considered noninformative. In order to improve the yield of MRD detection in these patients, we evaluated the usefulness of RT-PCR detection of c-erbB-2 expression. We were able to detect up to 1 MCF-7 cell (positive for c-erbB-2 expression) in a mixture of 1,000,000 CCRF-CEM cells (negative for c-erbB-2 expression). We evaluated the specificity of this technique in the peripheral-blood mononuclear cells (PBMCs) of 20 healthy women and found that 2 of these women were positive for c-erbB-2 expression. In the PBMCs of a group of 16 women with breast cancer, 25% of the samples were positive for c-erbB-2 expression before chemotherapy. Except for race (P = 0.017), no other significant correlations were found, including c-erbB-2 expression in the primary tumor by immunoperoxidase. Interestingly, in the subgroup of 6 patients for whom this technique was informative, we found that 80% of the samples obtained while on chemotherapy were negative compared to only 10% obtained off treatment (P = 0.017). Additionally, 2 patients for whom CK-19 expression was noninformative had at least 1 c-erbB-2-positive sample. We conclude that this technique might be useful for MRD detection in breast cancer patients, but further studies are necessary to confirm our findings.