Calbindin‐D_28k

Abstract

BACKGROUNDThe expression of the Ca2+‐binding protein calbindin‐D28k was analyzed in medulloblastomas in relation to clinical features and other biologic markers related to cell proliferation, differentiation, p53, and cerebellar developmental regulated gene expression.METHODSImmunohistochemistry was carried out on histologic slides from a first retrospective series of 29 nonmetastatic and 10 metastatic medulloblastoma formalin‐fixed, paraffin‐embedded tissues, using specific antibodies against calbindin‐D28k, calretinin, α‐parvalbumin and β‐parvalbumin, and S100 proteins. Informed consent was obtained from the subjects and/or guardians. Other biologic markers for differentiation, cell proliferation, the expression of the p53 tumor suppressor gene protein, and cerebellar developmental regulated genes were similarly investigated. A second series of 16 medulloblastomas from young patients (younger than 15 years) was added in order to validate the results obtained in the first series.RESULTSOf all the markers investigated, only calbindin‐D28k was significantly associated with prognosis. Survival and remission (i.e. recurrence free) time analysis performed on all the cases (n = 55) confirmed a high risk of death (P = 0.004) and recurrence (P = 0.003) associated with calbindin‐positivity. As calbindin‐positivity was predominantly observed in tumors from young patients, the authors confirmed its prognostic value in the subgroup of patients younger than 15 years (n = 37). Cox regression analysis showed a significant and independent prognostic value for calbindin expression and, to a lesser extent, the type of surgery (total or subtotal). Three risk groups were thus identified, distinguishing among the cases characterized by a total resection and calbindin‐negativity (good prognosis), by a subtotal resection and calbindin‐negativity (intermediary), and by calbindin‐positivity (bad prognosis).CONCLUSIONSThe current study suggests that calbindin‐positive medulloblastomas represent a subclass of aggressive tumors more frequently seen in younger patients. Cancer 2002;95:410–9. © 2002 American Cancer Society.DOI 10.1002/cncr.10666

Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial

“…33 Although most human adult tissues do not express CALB1 , its ectopic expression has been observed in several cancer types. 34,35 Recent functional studies have demonstrated a novel oncogenic activity of CALB1 where it binds MDM2 to enhance MDM2-mediated suppression of p53 signaling. 34 This is especially important in the context of DD-LPS, as MDM2 overexpression, leading to p53 degradation, is a hallmark of this disease.…”