title: Bax mutation and overexpression inversely correlate with immature phenotype and prognosis of childhood germ cell tumors.
abstract: Primary childhood germ cell tumors (GCTs) represent a rare and heterogeneous group of tumors that varies in histologic differentiation, age of presentation and clinical outcome. In malignant neoplasms, apoptosis is a prognostic marker and a predictive factor of response to therapy. Therefore, the study of the expression and mutation of molecules involved in the regulation of apoptosis could be useful in order to both predict the clinical outcome and design self-tailored therapeutic approaches. We retrospectively analysed tissue samples of 54 childhood GCTs. The expression of p53 and BAX protein was assessed by immunohistochemistry (IHC). Moreover, we investigated the presence of mutations in the BAX and p53 genes SSCP-PCR and direct sequencing. IHC analysis of BAX protein expression showed that 14 out of 54 tumors (26%) had no BAX protein expression, in the remaining 40 patients (74%) the intensity of BAX was low in 20 patients (37%) and high/intermediate in 20 (37%). BAX was mutated in 6 patients. p53 was expressed in 43 patients (79.6%), was not detectable in the remaining 11 (20.4%) and mutated in only 3 patients. p53 mutational status and expression were not correlated to the overall survival (OS). On the other hand, both IHC score and mutations for BAX were correlated to sacrococcygeal primary localization. BAX mutations were inversely correlated with OS (p=0.0419) while BAX IHC intensity was directly correlated with OS (p=0.0376). The stratification for histotype showed a direct correlation between BAX IHC and OS in both immature teratoma (p=0.045) and mixed malignant GCT (p=0.010) while the correlation was lost in mature teratoma (p=0.300). These results indicate that both mutations and BAX protein levels are useful molecular biological markers for prognosis and clinical management of pediatric GCT.
authors: Pediatric Oncology Service, Pediatric Department, II University of Naples, Naples, Italy.
authors: Raffaele
authors: R
authors: Addeo
authors: Stefania
authors: S
authors: Crisci
authors: Velia
authors: V
authors: D'Angelo
authors: Bruno
authors: B
authors: Vincenzi
authors: Fiorina
authors: F
authors: Casale
authors: Guido
authors: G
authors: Pettinato
authors: Vittoria
authors: V
authors: Donofrio
authors: Renata
authors: R
authors: Boldrini
authors: Rita
authors: R
authors: Alaggio
authors: Paola
authors: P
authors: Collini
authors: Roberta
authors: R
authors: Bertorelle
authors: Maria Teresa
authors: MT
authors: Di Tullio
authors: Michele
authors: M
authors: Caraglia
authors: Monica
authors: M
authors: Terenziani
authors: Margherita
authors: M
authors: Lo Curto
authors: Paolo
authors: P
authors: Indolfi
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D016158:Genes, p53; D006801:Humans; D007120:Immunochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C494826:BAX protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein