RESUMO
The present study deals with the characterization of hormone-sensitivity in pregnancy-associated breast cancers (PBCs). This characterization was carried out in 22 PBCs as opposed to 88 non-pregnancy-associated breast cancers (NPBCs). For this study, we used the digital cell image analysis of Feulgen-stained nuclei to assess the type of hormone-sensitivity. In a previous study it was demonstrated that the chromatin pattern in breast cancers is related to the amounts of estrogen receptors they contain. Our results demonstrated that the quantitative description of the chromatin pattern by means of 15 parameters (relating to morphometric, densitometric, and textural features) made it possible to identify typical cell nuclei populations in the PBC and NPBC groups. The use of specific statistical analyses (principal-components and discriminant) made it possible to quantify the proportion of each cell nucleus type in the PBCs. Furthermore, of the 22 PBCs under study, 13 contained a large majority of cell nuclei whose chromatin pattern was characteristic of hormone-sensitive cells, while 5 cases contained a large majority of typically hormone-insensitive ones. The remaining 4 cases contained a relatively similar proportion of typically hormone-sensitive and insensitive cell nuclei. The quantitative chromatin pattern description thus made it possible to characterize the hormone-sensitivity level in PBCs, whereas DNA ploidy level determination did not enable any such characterization to be carried out. The chromatin pattern assay described here, which enables hormone-sensitive pregnancy-associated breast cancers to be identified from hormone-insensitive ones independently from biochemical assays, should help the physician regarding therapy adaptation.
Assuntos
Neoplasias da Mama/genética , Cromatina , DNA de Neoplasias/análise , Neoplasias Hormônio-Dependentes/genética , Ploidias , Complicações Neoplásicas na Gravidez , Neoplasias da Mama/química , Neoplasias da Mama/ultraestrutura , Núcleo Celular/patologia , Feminino , Humanos , Citometria por Imagem/métodos , Análise Multivariada , Neoplasias Hormônio-Dependentes/química , Neoplasias Hormônio-Dependentes/ultraestrutura , Gravidez , Receptores de Estrogênio/análiseRESUMO
Chemotherapy-induced morphonuclear modifications were monitored in vivo by means of the digital cell image analysis of Feulgen-stained nuclei. Two experimental models were used, i.e. the P388 mouse leukaemia and the MXT mouse mammary carcinoma. The drugs used were doxorubicin, etoposide and cyclophosphamide. The results indicate that the chemotherapy induced a significant decrease in the MXT tumour growth and a significant increase in the survival of the P388 leukaemic mice. These effects were accompanied at the morphonuclear level by an increase in the nuclear area, by modifications in the DNA content in accordance with the effects of the drugs on the cell cycle and by several modifications in the chromatin texture in accordance with the model or the drugs studied. While there were neither homogeneous morphonuclear changes in all treatment groups nor clearcut correlations between the morphonuclear changes and tumour growth or the survival of the animals, the present study nevertheless shows that it is possible, at least partly, to monitor in vivo certain chemotherapy-induced effects occurring at the morphonuclear level, and subsequently to obtain information on the mode of action of the drugs.
Assuntos
Antineoplásicos/farmacologia , Núcleo Celular/efeitos dos fármacos , Leucemia P388/patologia , Neoplasias Mamárias Experimentais/patologia , Animais , Núcleo Celular/ultraestrutura , Cromatina/efeitos dos fármacos , Ciclofosfamida/farmacologia , Feminino , Leucemia P388/tratamento farmacológico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Melfalan/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Análise MultivariadaRESUMO
The present study describes the setting up of a new score which makes it possible objectively to grade ductal breast carcinomas, i.e. not-otherwise-specified (NOS) cancers, on cellular material from fine-needle aspirations (FNAs). For this purpose FNAs from 252 patients--with NOS breast cancers--were smeared onto histological slides, fixed in an ethanol-formolacetic acid mixture, Feulgen-stained and analysed by means of a cell image processor. Four parameters were taken into account in setting up the score, namely the cytological prognostic grade (CPM) of malignancies similar to the Scarff-Bloom-Richardson (SBR) grading, the nuclear area (NA), the DNA index (DI) and the DNA histogram type (DHT). Each of these four parameters was considered as a "sub-score" which may take three values, i.e. 1, 2 and 3. The final result may thus range from 4 to 12. Subscores of 4 and 5 correspond to a cytological score of I, subscores of 6, 7 and 8 to a cytological score of II, sub-scores of 9 and 10 to a cytological score of III, and sub-scores of 11 and 12 to a cytological score of IV. In the present study, the results show 17% of CPM grade 1.52% of CPM grade II and 31% of CPM grade III cancers. All the cases exhibiting a cytological score of IV (5%) fully fit in with the CPM grade III cancers. In the same way, none of the cases exhibiting a score of I fit in with CPM grade III cancers. The cancers with a CPM grade II fit in with the scores of II and III. It thus seems possible to convert a three-value malignancy grading system (CPM and/or SBR grading) into a four-value one (cytological score). The main advantage in this latter type of system is that it becomes possible to split up the over-large group of CPM grade II cancers. As things stand, we are unable to give any prognostic value for the score proposed here because our study is prospective only. A study of this type has been necessary so as to provide against problems connected with ways of preserving specimens that might be used in a retrospective study. The bank of clinical and biological data now in existence must be allowed to mature for a number of years before the prognostic worth of the cytological score can be established, always assuming that such a value exists.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Núcleo Celular/patologia , DNA de Neoplasias/análise , Corantes de Rosanilina , Biópsia por Agulha , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Corantes , Feminino , Humanos , Ploidias , Valor Preditivo dos Testes , Prognóstico , Coloração e RotulagemRESUMO
The morphonuclear characteristics (nuclear size and chromatin pattern), the proliferation index and the ploidy level were characterized in a series of 46 breast tumors including medullary (5 cases), papillary (6 cases), lobular (27 cases), colloid (4 cases) and comedo- (4 cases) carcinomas. The quantitative assessments were carried out by means of digital cell image analyses of Feulgen-stained nuclei from imprint smears. The results show that monovariate analyses (one-way variance analyses) were much less potent than multivariate analyses (principal components analyses followed by the canonical transformation of the data and discriminant analyses) in assessing the morphonuclear characteristics of these breast tumors. The multivariate analyses indicated that there might be a level of malignancy which increases according to the sequence papillary and medullary and colloid carcinomas-->comedocarcinomas-->lobular carcinomas. This assertion is corroborated by the ploidy-level-related results which revealed a higher proportion of highly aneuploid cases in the group of lobular carcinomas than in the group which included medullary, papillary and colloid carcinomas. However, since highly aneuploid cases were also encountered in this latter low malignancy level group, we expressed the hypothesis firstly that aneuploidy reflects two distinct biological properties, i.e. the aggressiveness of a tumor and its age, and secondly that a highly aneuploid but low malignancy tumor should correspond to old degenerating tumors.