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QuantificaĆ§Ć£o celular em meningiomas
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Os meningiomas sĆ£o a segunda neoplasia mais frequente no SNC, e representa 26% de todos os tumores intracranianos. EstĆ£o divididos em trĆŖs graus histolĆ³gicos I, II e III de acordo com os critĆ©rios de anaplasia definidos pela OMS, no entanto, e para um diagnĆ³stico inequĆvoco do grau de anaplasia Ć© necessĆ”rio a contribuiĆ§Ć£o de indicadores quantitativos.
A atividade proliferativa de qualquer tumor pode ser determinada pela utilizaĆ§Ć£o de tĆ©cnicas de imunohistoquĆmica com o anticorpo MM1, que deteta um epĆtopo do antigĆ©nio Ki-67, uma proteĆna nuclear, presente em toda a fase ativa do ciclo celular (G1,S,G2 e M). Contudo, o Ćndice de Ki-67 nĆ£o Ć© utilizado como critĆ©rio de anaplasia, devido Ć variabilidade das tĆ©cnicas de imunohistoquĆmica em diferentes laboratĆ³rios. A utilizaĆ§Ć£o da densidade celular, um novo mĆ©todo quantitativo, permite superar este problema, uma vez que a contagem celular Ć© independente do patologista.
O objetivo primĆ”rio deste estudo foi determinar a densidade celular de uma amostra de 250 casos de meningioma, e quantificar o Ćndice proliferativo, com o anticorpo ki-67. Pretende-se apĆ³s esta determinaĆ§Ć£o relacionar estes dois dados quantitativos entre si, e com o grau histolĆ³gico, com os critĆ©rios da OMS. Como objetivo secundĆ”rio pretendeu-se estabelecer valores, com a quantificaĆ§Ć£o da densidade e do Ćndice proliferativo, para os quais fosse possĆvel diferenciar entre os vĆ”rios diagnĆ³sticos histolĆ³gicos, melhorando a capacidade de dianĆ³stica, tornando a classificaĆ§Ć£o histolĆ³gica, um pouco menos subjectiva.
Foram realizados tissue microarrays, dos diferentes casos, apĆ³s selecĆ§Ć£o microscĆ³pica das Ć”reas mais representativas.
Dos 250 meningiomas analisados, 140 foram de grau I, 79 de grau II e 31 de grau III. O rĆ”cio entre indivĆduos do sexo feminino e masculino foi de 1,86:1. A anĆ”lise dos resultados deste estudo demonstrou que a mĆ©dia do Ćndice proliferativo foi de 3,85Ā±4,97%, 2,70Ā±2,60% e 1,81Ā±2,52%, em meningiomas anaplĆ”sicos, atĆpicos e benignos, respetivamente (p=0,001).
A mĆ©dia da densidade celular foi de 14,8 Ā± 3,68 cĆ©lulas/ 100Ī¼m2, 13,5 Ā± 2,80 cĆ©lulas/ 100Ī¼m2 e 12,5Ā±0,04 cĆ©lulas/100Ī¼m2 para meningiomas anaplĆ”sicos, atĆpicos e benignos, respetivamente (p<0,0001).
A anĆ”lise preliminar das curvas ROC demonstrou que o ponto de corte obtido foi de 1,63% para o Ćndice de Ki-67 e de 14,2 cĆ©lulas/100Ī¼m2 para a densidade celular.
Foram encontradas diferenƧas significativas na expressĆ£o do Ki-67 e densidade celular entre os subtipos de meningiomas de grau I, sendo a variante meningotelial aquela obteve uma expressĆ£o superior aos restantes subtipos.
Meningiomas represent the second most common central nervous system neoplasms in adults and account for 26% of all primary brain tumors. Meningiomas are divided histologically, by morphologic features, into three grades by anaplastic criteria defined by the World Health Organization (WHO). However, for an unequivocal diagnosis of the histological grade is necessary a contribution of quantitative indicators. Proliferative activity in tumors can be determined by immunohistochemistry using the MM1 antibody that is to be able to detect an epitope on the Ki-67 antigen, a nuclear protein present only during active phase of the cell cycle (G1, S, G2, and M). Nevertheless, the use of Ki-67 immunohistochemistry raises some questions on the reproducibility due mainly to the variability of different techniques between different laboratories. The use of cell density, a new quantification parameter, could be a new method to supporting the diagnostic, once itās independent of pathologist. Therefore, the aim of this study was to explore the relationship between some quantitative histological features of meningioma, cell density and Ki-67 staining index on 250 patients with meningioma, in the most common histological types. The secondary aim was to determine the optimal cut-off value for cell density and Ki-67 Li. Appropriate areas of the meningioma tissue were selected using a tissue microarray and analyzed by automated counting cells with image J software on digital images. Of 250 meningiomas analyses, were 140 grade I, 79 grade II and 31 grade II. Female to male ratio was 1,86:1. The results of our investigations indicate that the mean Ki-67 labeling index was 3,85Ā±4,97%, 2,70Ā±2,60% and 1,81Ā±2,52% to anaplastic, atypical and benign meningioma, respectively. There was significant correlation between Ki-67 levels and tumor subtypes (p=0,001). The mean of cell density was 14,8 Ā± 3,68 core/100Ī¼m2, 13,5 Ā± 2,80core/100Ī¼m2 and 12,5Ā±0,04 core/100Ī¼m2 to anaplastic, atypical and benign meningioma, respectively. There was significant correlation between cell density and tumor subtypes (p<0,0001) The analysis of ROC curve showed that the optimal cut-off value for Ki-67 was 1,63% and for cell counting was 14,2 core/100Ī¼m2. We found differences between meningioma subtypes of grade I and Ki-67 expression. Meningothelial meningiomas had the highest mean value for Ki-67. The Ki-67 LI is one important tool in addition to routine histological evaluation of meningioma, but a combination with other methods will improve it. However, more extended studies are needed for approval of this suggestion.
Meningiomas represent the second most common central nervous system neoplasms in adults and account for 26% of all primary brain tumors. Meningiomas are divided histologically, by morphologic features, into three grades by anaplastic criteria defined by the World Health Organization (WHO). However, for an unequivocal diagnosis of the histological grade is necessary a contribution of quantitative indicators. Proliferative activity in tumors can be determined by immunohistochemistry using the MM1 antibody that is to be able to detect an epitope on the Ki-67 antigen, a nuclear protein present only during active phase of the cell cycle (G1, S, G2, and M). Nevertheless, the use of Ki-67 immunohistochemistry raises some questions on the reproducibility due mainly to the variability of different techniques between different laboratories. The use of cell density, a new quantification parameter, could be a new method to supporting the diagnostic, once itās independent of pathologist. Therefore, the aim of this study was to explore the relationship between some quantitative histological features of meningioma, cell density and Ki-67 staining index on 250 patients with meningioma, in the most common histological types. The secondary aim was to determine the optimal cut-off value for cell density and Ki-67 Li. Appropriate areas of the meningioma tissue were selected using a tissue microarray and analyzed by automated counting cells with image J software on digital images. Of 250 meningiomas analyses, were 140 grade I, 79 grade II and 31 grade II. Female to male ratio was 1,86:1. The results of our investigations indicate that the mean Ki-67 labeling index was 3,85Ā±4,97%, 2,70Ā±2,60% and 1,81Ā±2,52% to anaplastic, atypical and benign meningioma, respectively. There was significant correlation between Ki-67 levels and tumor subtypes (p=0,001). The mean of cell density was 14,8 Ā± 3,68 core/100Ī¼m2, 13,5 Ā± 2,80core/100Ī¼m2 and 12,5Ā±0,04 core/100Ī¼m2 to anaplastic, atypical and benign meningioma, respectively. There was significant correlation between cell density and tumor subtypes (p<0,0001) The analysis of ROC curve showed that the optimal cut-off value for Ki-67 was 1,63% and for cell counting was 14,2 core/100Ī¼m2. We found differences between meningioma subtypes of grade I and Ki-67 expression. Meningothelial meningiomas had the highest mean value for Ki-67. The Ki-67 LI is one important tool in addition to routine histological evaluation of meningioma, but a combination with other methods will improve it. However, more extended studies are needed for approval of this suggestion.
DescriĆ§Ć£o
Tese de mestrado, NeurociĆŖncias, Universidade de Lisboa, Faculdade de Medicina, 2016
Palavras-chave
Meningiomas ImunohistoquĆmica Ćndice proliferativo (Ki-67) Indicadores quantitativos Teses de mestrado - 2016