P53 in Epithelioid Angiomyolipoma: An Immunohistochemistry Study and Gene Mutation Analysis
Zhanyong Bing, Yuan Yao, Theresa Pasha, John E Tomaszewski, Paul J Zhang. Hospital of the University of Pennsylvania, Philadelphia; University of Buffalo, Buffalo
Background: Epithelioid AML (EAML) is a rare variant of AML and is more often associated with aggressive behaviors. The pathogenesis of EAML has been poorly understood. The expression and mutation analysis of p53 in EAML has only been described in case reports with conflicting results.
Design: We studied p53 expression and gene mutation in EAMLs by immunohistochemistry, single-strand conformation polymorphism (SSCP) and direct sequencing in paraffin materials from 8 EAMLs. The score for p53 nuclear staining was calculated by using the Allred score system. A group of typical AMLs was also analyzed for comparison.
Results: Of the 8 patients, 5 were from men, 3 from women, with an average age of 41.9+/-17.7 years. 5 tumors arose from kidneys, one each from heart, liver and uterus. 2 patients had history of tuberous sclerosis, 4 had metastasis and 1 had local recurrence. All EAMLs and 5 of 12 typical AMLs were positive for p53 immunoexpression. EAMLs showed much stronger p53 nuclear staining (Allred score 6.4 +/- 2.5) than the typical AML (2.3 +/- 2.9) (p<0.01). There was no p53 SSCP identified in either EAMLs or 8 typical AMLs. P53 mutation analysis by direct sequencing of exons 5-9 showed 4 mutations in 3 of 8 EAMLs but none of 8 typical AMLs. The mutations included two missense mutations in one case and two silent mutations in another two cases. For the two cases with silent mutations, both of them were renal tumors. For one case (case 1), in exon 5 codon 154 was changed from GGC to GGG, which was a silent mutation coding for amino acid glycine. For the other case, the silent mutation involved exon 6 codon 218 which was changed from GTG to GTT (both of the codons coding same amino acid valine). The case with two missense mutation was a hepatic PeComa. Both mutations involved the exon 5, one involving codon 165 with change from CAG to CAC (coding amino acid changed from glutamine to histidine), and the other involving codon 182 with change from TGC to TAC (coding amino acid changed from cysteine to tyrosine).
Conclusions: EAMLs had more frequent and stronger p53 expression than the typical AMLs. Four new p53 mutations were identified in 3 of 8 EAMLs, two of which were missense mutations found in a hepatic PeComa, two were silent mutations involving two renal EAMLs. The finding of abnormal p53 expression and mutations might be contributed to its less predictable behavior. However, the abnormal p53 expression cannot be entirely explained by p53 mutations in the exons examined in EAML.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 99, Wednesday Morning