Alterations of the p53 and PIK3CA/AKT/mTOR pathways in angiosarcomas: A pattern distinct from other sarcomas with complex genomics Journal Article
| Authors: | Italiano, A.; Chen, C. L.; Thomas, R.; Breen, M.; Bonnet, F.; Sevenet, N.; Longy, M.; Maki, R. G.; Coindre, J. M.; Antonescu, C. R. |
| Article Title: | Alterations of the p53 and PIK3CA/AKT/mTOR pathways in angiosarcomas: A pattern distinct from other sarcomas with complex genomics |
| Abstract: | BACKGROUND: The p53 and phosphoinositide-3-kinase, catalytic, alpha polypeptide/v-akt murine thymoma viral oncogene homolog/mechanistic target of rapamycin (PIK3CA/AKT/mTOR) pathways frequently are altered in sarcoma with complex genomics, such as leiomyosarcoma (LMS) or undifferentiated pleomorphic sarcoma (UPS). The scale of genetic abnormalities in these pathways remains unknown in angiosarcoma (AS). METHODS: The authors investigated the status of critical genes involved in the p53 and PIK3CA/AKT/mTOR pathways in a series of 62 AS. RESULTS: The mutation and deletion rates of tumor protein 53 (TP53) were 4% and 0%, respectively. Overexpression of p53 was detected by immunohistochemistry in 49% of patients and was associated with inferior disease-free survival. Although p14 inactivation or overexpression of the human murine double minute homolog (HDM2) were frequent in LMS and UPS and could substitute for TP53 mutation or deletion, such alterations were rare in angiosarcomas. Phosphorylated ribosomal protein S6 kinase (p-S6K) and/or phosphorylated eukaryotic translation initiation factor 4E binding protein 1 (p-4eBP1) overexpression was observed in 42% of patients, suggesting frequent activation of the PIK3CA/AKT/mTOR pathway in angiosarcomas. Activation was not related to intragenic deletion of phosphatase and tensin homolog (PTEN), an aberration that is frequent in LMS and UPS but absent in angiosarcomas. CONCLUSIONS: The current results indicated that angiosarcomas constitute a distinct subgroup among sarcomas with complex genomics. Although TP53 mutation and PTEN deletion are frequent in LMS and UPS, these aberrations are rarely involved in the pathogenesis of angiosarcoma. © 2012 American Cancer Society. |
| Keywords: | immunohistochemistry; signal transduction; protein kinase b; s6 kinase; adult; human tissue; protein phosphorylation; aged; aged, 80 and over; middle aged; unclassified drug; major clinical study; gene deletion; mutation; disease free survival; gene; gene overexpression; genetic association; gene frequency; gene function; angiosarcoma; mutational analysis; hemangiosarcoma; phosphatidylinositol 3 kinase; protein p53; carcinogenesis; tumor suppressor gene; gene identification; nucleotide sequence; mammalian target of rapamycin; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; proto-oncogene proteins c-akt; pten phosphohydrolase; initiation factor 4e binding protein 1; genomics; gene inactivation; gene insertion; comparative genomic hybridization; pik3ca gene; proto-oncogene proteins b-raf; p53; protein p14; protein mdm2; proto-oncogene proteins c-mdm2; genes, p53; phosphatidylinositol 3-kinases; tor serine-threonine kinases; complex karyotype; phosphatase and tensin homolog; phosphoinositide-3-kinase, catalytic, alpha polypeptide; phosphatidylinositol 3 kinase catalytic alpha polypeptide; 4ebp1 gene; akt gene; hdm2 gene; mtor gene; p14 gene; ps6k gene |
| Journal Title: | Cancer |
| Volume: | 118 |
| Issue: | 23 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2012-12-01 |
| Start Page: | 5878 |
| End Page: | 5887 |
| Language: | English |
| DOI: | 10.1002/cncr.27614 |
| PROVIDER: | scopus |
| PMCID: | PMC3434269 |
| PUBMED: | 22648906 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 December 2012" - "CODEN: CANCA" - "Source: Scopus" |
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