Amalia Patereli

G1 cell cycle regulators in congenital melanocytic nevi. Comparison with acquired nevi and melanomas.

Background:  Congenital nevi are one of the known risk factors for the development of melanoma. However, the magnitude of the risk for both large and small congenital nevi is controversial.

Expression of epidermal growth factor receptor and HER-2 in pediatric embryonal brain tumors.

Background/Aims: Medulloblastomas (MBs), atypical teratoid rhabdoid tumors (AT/RTs) and central nervous system primitive neuroectodermal tumors (PNETs) are aggressive embryonal brain neoplasms in children with overlapping histological features but with different pathogenetic pathways. We set out to evaluate the role of epidermal growth factor receptor (EGFR), HER-2, Ki-67 and p53 in embryonal tumors. Material and Methods: We retrospectively evaluated 36 children with embryonic tumors (27 MBs, 7 AT/RTs and 2 supratentorial PNETs). The immunohistochemical expression of EGFR and HER-2 was correlated to histology, expression of the Ki-67/MIB-1 proliferative index, p53 tumor suppressor oncoprotein and prognosis. Results: High expression of Ki-67 was observed in all MBs being particularly increased (>50%) in 8 cases, while p53 protein was detected in 25/27 MBs showing a high expression in 16 cases. EGFR and HER-2 expression was observed in 10/27 and 17/27 MBs, respectively. High Ki-67/MIB-1 and p53 expression was revealed in all AT/RTs and PNETs, while EGFR and HER-2 were detected in 3/7 and 6/7 AT/RTs, respectively. The 5-year progression-free survival and overall survival were 55.5 and 69.2%, respectively. In MBs, the univariate analysis revealed that the Ki-67 index and male gender were both at a significant level related to the survival of the patient. In multivariate analysis, the Ki-67 index was the only independent predictive variable. Conclusions: The Ki-67 index was identified as a factor with independent prognostic power. EGFR and HER-2 expression is variable in embryonal tumors. HER-2 expression, in a considerable number of MBs and AT/RTs, suggests that HER-2 may be implicated in their pathogenesis representing a potential target for novel therapies.

The Role of Fast Cell Cycle Analysis in Pediatric Brain Tumors.

Cell cycle analysis by flow cytometry has not been adequately studied in pediatric brain tumors. We investigated the value of a modified rapid (within 6 min) cell cycle analysis protocol for the characterization of malignancy of pediatric brain tumors and for the differentiation of neoplastic from nonneoplastic tissue for possible intraoperative application. We retrospectively studied brain tumor specimens from patients treated at our institute over a 5-year period. All tumor samples were histopathologically verified before flow-cytometric analysis. The histopathological examination of permanent tissue sections was the gold standard. There were 68 brain tumor cases. All tumors had significantly lower G₀/G1 and significantly higher S phase and mitosis fractions than normal brain tissue. Furthermore low-grade tumors could be differentiated from high-grade tumors. DNA aneuploidy was detected in 35 tumors. A correlation between S phase fraction and Ki-67 index was found in medulloblastomas and anaplastic ependymomas. Rapid cell cycle analysis by flow cytometry is a promising method for the identification of neoplastic tissue intraoperatively. Low-grade tumors could be differentiated from high-grade tumors. Thus, cell cycle analysis can be a valuable adjunct to the histopathological evaluation of pediatric brain tumors, whereas its intraoperative application warrants further investigation.

In situ evidence of cellular senescence in Thymic Epithelial Cells (TECs) during human thymic involution

Cellular senescence, an age-related process in response to damage and stress, also occurs during normal development and adult life. The thymus is a central lymphoepithelial organ of the immune system that exhibits age-related changes termed thymic involution. Since the mechanisms regulating thymic involution are still not well elucidated, we questioned whether cellular senescence is implicated in this process. We demonstrate, for the first time in situ, that cellular senescence occurs during human thymic involution using SenTraGor™, a novel chemical compound that is applicable in archival tissue material, providing thus further insights in thymus histophysiology.

Immunohistochemical Expression of Cell Cycle/Apoptosis Regulators and Epidermal Growth Factor Receptor in Pediatric Intracranial Ependymomas

Intracranial ependymomas are the third most common primary brain tumor in children. We set out to investigate the expression of p-53, p-27, bcl-2, and epidermal growth factor receptor in 13 pediatric infratentorial ependymomas, in correlation with Ki-67/ MIB-1 proliferation index and prognosis. The median progression-free survival was 37.5 months, and the 5-year overall survival was 50%. There was a statistically significant higher expression of Ki-67 and p-53 index in anaplastic tumors. There was also a higher expression of p-27, bcl-2, and epidermal growth factor receptor in anaplastic tumors, but the difference was not statistical significant. No significant correlation was found between overall survival and level of expression of Ki-67, p-53, p-27, bcl-2, and epidermal growth factor receptor. Epidermal growth factor receptor detection in a considerable number of ependymomas probably reflects its role in the neoplastic transformation and can serve as a therapeutic target.

Pediatric Embryonal Tumors: Prognostic Role of Cyclin A and B1 Proteins

Embryonal brain tumors account for 20–25% of all brain neoplasms in children and represent the second most frequent group of pediatric brain tumors. Embryonal tumors include medulloblastoma, atypical teratoid/rhabdoid tumor and supratentorial primitive neuroectodermal tumor. These tumors are highly malignant and there is a significant long-term treatment related morbidity. Various biologic parameters have been related to outcome. Cyclins are a group of proteins which are periodically synthesized and degraded during the cell cycle. They affect progression in the cell cycle through activation of cyclin–dependent kinases forming heterodimers. This review focus on the prognostic role of the mytotic cyclins, namely cyclins A and B1, in pediatric embryonal tumors. Based on recent evidence there is a significant expression of cyclin A and cyclin B1 in embryonal tumors, whereas the expression patterns of these cyclins correlate with patient’s prognosis.