Analysis of p53 and mdm2 proteins in malignant fibrous histiocytoma in absence of gene alteration: prognostic significance.
TP53 and MDM2 genes and their protein expression were evaluated in frozen and paraffin-embedded tissue from 27 patients with malignant fibrous histiocytoma to elucidate the relationship between them, their implication in tumor progression mechanisms and their possible diagnostic-prognostic value in malignant fibrous histiocytoma. Single-strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction-amplified DNA were used to establish two TP53 mutations (7.4%): a point mutation and a 63-bp duplication. Amplification of the MDM2 gene was observed in two tumors (7.4%) by means of Southern-blot analysis, one of them also carrying the TP53 point mutation. Immunohistochemical and Western-blot techniques were used to study nuclear accumulation of p53 and mdm2 proteins: 11 cases (40.7%) with p53 protein expression and thirteen cases (48.1%) with mdm2 protein expression were detected. We confirmed overexpression of mdm2 protein in eight of ten cases (80%) with p53 protein expression without TP53 gene mutation. Statistical analysis shows that simultaneous co-expression of p53 and mdm2 in malignant fibrous histiocytoma is significantly correlated with survival in absence of gene alteration in contrast to the lack of statistical correlation with survival of p53 protein expression alone.
Molina
P
P
Department of Pathology, Medical School, University of Valencia, Spain.
Pellín
A
A
Navarro
S
S
Boix
J
J
Carda
C
C
Llombart-Bosch
A
A
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D018219:Histiocytoma, Benign Fibrous / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012983:Soft Tissue Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2