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Le Grazie di Ancona, Italy

Caldarella A.,Institute for Study and Cancer Prevention ISPO | Buzzoni C.,Institute for Study and Cancer Prevention ISPO | Crocetti E.,Institute for Study and Cancer Prevention ISPO | Bianchi S.,University of Florence | And 7 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2013

Introduction: The special types of breast cancer seem to have not only distinct morphological features but also distinct biological features. Materials and methods: Women diagnosed with a first primary invasive breast cancer in the 2004-2005 period were identified through Tuscan Cancer Registry. Information on age, tumor size, lymph node status, histological type and grade, hormonal receptors, HER2 immunohistochemical expression were collected. Five subtypes were defined: luminal A, luminal B HER2+, luminal B HER2-, triple negative, and HER2 positive. The association between the histological type and molecular subgroups was assessed by a Fisher's exact test, and a multinomial logistic regression model was used. Results: Out of 1,487 patients, 34 % were luminal A subtype, 25 % luminal B HER2-, 11 % luminal B HER2+, 19 % triple negative, and 10.2 % HER2+; 58.5 % of cancers were ductal NOS types. With luminal A as reference, histological types distribution was significantly different between the subgroups. Mucinous, tubular, and cribriform histotypes were found among luminal A cancers more than in other subgroups; all medullary carcinomas were triple negative cancers. Pathological stage at diagnosis was more advanced, and histological grade was lower among subgroups other than luminal A. Conclusions: Significant association between breast cancer histotypes and molecular subgroups was found. © 2012 Springer-Verlag Berlin Heidelberg.


Caldarella A.,Institute for Study and Cancer Prevention ISPO | Puliti D.,Institute for Study and Cancer Prevention ISPO | Crocetti E.,Institute for Study and Cancer Prevention ISPO | Bianchi S.,University of Florence | And 7 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2013

Introduction: In a population-based screening program, a percentage of tumors remain undetected; these tumors comprise a heterogeneous group, and they are more likely to have adverse prognostic features. The aim of this study was to identify differences in biological characteristics of screen-detected versus interval breast cancers in a population-based screening program according to molecular subtypes. Materials and methods: We analyzed the population-based data from a long-running screening program in the area of Florence. Data on screening history and on age, T and N status, grade, histotype, hormonal status and Ki-67 and HER2 expression were retrieved. Subtypes of breast cancer were defined on the expression of ER, PR, Ki-67 and HER2: luminal A if ER/PR+, HER2- and Ki67 <14 %, luminal B (HER2 negative) if ER/PR+, HER2- and Ki67 ≥14 %, luminal B (HER2 positive) if ER/PR+ and HER2+, triple negative if ER/PR-and HER2-, HER2 positive if ER/PR- and HER2+. Association between molecular subtypes and mode of detection will be evaluated by a logistic regression model adjusted for the potential confounding variables. Results: Information about biomarkers was known for 277 cases, 211 screening-detected and 66 interval cancers. Among interval cases, the triple-negative cancers were more represented than luminal A (OR = 3.52; CI, 1.112-11.13; p = 0.0319), while the proportion of HER2+ was quite similar (OR = 1.57; p = 0.4709). Conclusion: Although made on a small number of cases, our results suggest a difference in distribution of molecular subtypes according to mode detection, confirming the results of earlier studies. © 2012 Springer-Verlag.


Simoes B.M.,CIC Biomagune | Piva M.,CIC Biomagune | Iriondo O.,CIC Biomagune | Comaills V.,CIC Biomagune | And 5 more authors.
Breast Cancer Research and Treatment | Year: 2011

There is increasing evidence that breast cancers contain tumor-initiating cells with stem cell properties. The importance of estrogen in the development of the mammary gland and in breast cancer is well known, but the influence of estrogen on the stem cell population has not been assessed. We show that estrogen reduces the proportion of stem cells in the normal human mammary gland and in breast cancer cells. The embryonic stem cell genes NANOG, OCT4, and SOX2 are expressed in normal breast stem cells and at higher levels in breast tumor cells and their expression decreases upon differentiation. Overexpression of each stem cell gene reduces estrogen receptor (ER) expression, and increases the number of stem cells and their capacity for invasion, properties associated with tumorigenesis and poor prognosis. These results indicate that estrogen reduces the size of the human breast stem cell pool and may provide an explanation for the better prognosis of ER-positive tumors. © 2010 Springer Science+Business Media, LLC.


Bianciardi G.,University of Siena | Pontenani F.,University of Siena | Vassallo L.,University of Siena | Tacchini D.,University of Siena | And 2 more authors.
Microscopy Research and Technique | Year: 2016

For diagnostic purposes, cryofixation of tissues is a daily routine technique to investigate rapidly about the presence of tumours during a surgical procedure in patients. We performed morphometric analysis of cryofixed muscular tissues according to different techniques. About 1,000 muscle fibers and 1,493 nuclei, were automatically examined. After freezing, ice tissue interfaces shrinkage of the cells were present. Liquid isopentane or liquid nitrogen produced a statistical increase of fractal dimension, D, of the ice-tissue interfaces, P<0.001 respect to the formalin-fixed samples, cryofixation performed inside the cryostat chamber at t=-20°C produced a D value close to the formalin-fixed samples. Shrinkage of the muscle fibers was higher in the samples cryofixed inside the cryostat chamber (P<0.001). Cryofixation inside cryostat or by liquid nitrogen caused decreases of the nuclei dimensions and altered nuclear morphology (P<0.01), liquid isopentane appeared not affecting the nuclei of the fibers. Cryofixation inside the cryostat chamber produced the highest shrinkage but it was reduced performing cryofixation in liquid nitrogen or isopentane. Freezing damage inside the muscle cells was absent in the samples cryofixed inside the cryostat, it was present after cryofixation by liquid nitrogen or isopentane. Subcellular components like the nuclei were preserved by isopentane. This paper present, for the first time, an objective method able to quantify and characterize the damages produced by cryofixation in biological sample for intraoperative consultation. © 2016 Wiley Periodicals, Inc.


Bianciardi G.,University of Siena | Pontenani F.,University of Siena | Tripodi S.,Pathological Anatomy
Current Bioinformatics | Year: 2015

Cryofixation of tissues in a cryostat chamber is a routine technique to investigate rapidly about the presence of tumours during a surgical procedure in patients (intraoperative consultation). The tissue is placed without cryoprotectant in contact with a cooled metal block inside the cryostat used for cutting and preparing the specimen, without or with a heavy weight. Until now, quantitative studies of the damages produced by freezing in intraoperative consultation are lacking. To obtain quantitative indexes we have performed fractal analysis (local fractal dimension, D0 and entropy, D1) of the cryofixed muscular tissues in comparison to formalin-fixed samples. Seventy-two microscopic fields or 700 muscle fibres were automatically examined. After freezing at t = 20 °C using an heavy weight, large voids inside the cells (ice-tissue interfaces) were present, while without the use of the weight the fibres collapse (shrinkage). Fractal analysis revealed the presence of a multifractal structure. In the formalin-fixed samples, at large scale the muscle tissue D0 and D1 reached the values of the Diffusion-Limited Aggregation process. At large scale, after cryofixation using the weight, D0 and D1 statistical increased (p<0.01; p<0.01), respect to the formalin-fixed samples, while, without the weight, the values were close to the ones of formalin-fixed samples. At low scale, without the weight, D0 and D1decreased statistically (p<0.01) compared to the formalin-fixed samples, while, with the weight, the values were close to the ones of formalin-fixed samples. Large and low scales accurately quantified the amount of ice-tissue interfaces and cell shrinkage, respectively. © 2015 Bentham Science Publishers.

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