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Conference Paper: Loss of ATRX and DAXX expression identifies poor prognosis for uterine smooth muscle tumors

TitleLoss of ATRX and DAXX expression identifies poor prognosis for uterine smooth muscle tumors
Authors
KeywordsMedical sciences biology
Issue Date2014
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/modpathol/
Citation
The 103rd Annual Meeting of the United States and Canadian Academy of Pathology (USCAP 2014), San Diego, CA., 1-7 March 2014. In Modern Pathology, 2014, v. 27 suppl. 2, p. 308A, abstract no. 1272 How to Cite?
AbstractBACKGROUND: Uterine smooth muscle tumors of uncertain malignant potential (STUMP) have variable pathological features and recurrence rates, which results in considerable treatment uncertainty. New prognostic markers are required. Alternative lengthening of telomeres (ALT) maintenance is associated with poor survival in some soft tissue leiomyosarcomas (LMS). ALT maintenance is related to mutations in ATRX (α-thalassemia/mental retardation syndrome X-linked) and DAXX (death-domainassociated protein) genes and their respective proteins are involved in remodelling of chromatin structure. ALT maintenance also produces extremely long protein structures ALT-associated PML bodies (APB). DESIGN: 40 LMS, 17 STUMPs, and 10 leiomyomas (LM) were studied and follow-up data obtained. They were screened for APBs by immunofl uorescent study (anti-PML, H-238, Santa Cruz). Telomere DNA was detected using a Cy3-labelled PNA probe (Life Technologies, Carlsbad). APB positive occur when when both PML protein and telomeric DNA are seen in the nucleus in≥ 0•5% of cells. Immunohistochemistry was done with ATRX and DAXX antibodies (respectively HPA001906 & HPA008736 Sigma-Aldrich, St Louis). Staining in <10% of nuclei were considered loss of expression. p53 (DO-7, Cell Marque) was also done. RESULTS: Mean patient ages and tumor sizes for LMS, STUMP and LM were respectively 49.5, 44.1 and 50.4 years, and 10, 8.5, and 3.5 cm. Recurrence/death was seen in 35% (6/17) STUMPs and 60% (24/40) LMS. No LMs recurred. For STUMPs, 24% (4/17) were APB+ve and 30% (5/17) overexpressed p53. Loss of staining for ATRX and DAXX was seen in 30% (5/17) and 12% (2/17), respectively. For LMS, 40% (16/40) were APB+ve and 42% (17/40) overexpressed p53. Loss of staining for ATRX and DAXX was seen in 58% (23/40) and 15% (6/40), respectively. All 6 STUMPs and 92% (22/24) LMS followed by recurrence/death showed loss of ATRX or DAXX expression. 60% (17/28) of these cases with adverse outcome were also APB positive. Overexpression of p53 (p=0.001) and loss of ATRX and/or DAXX expression (p<0.05) were associated with a poor outcome. CONCLUSIONS: Loss of ATRX or DAXX expression in uterine smooth muscle tumors identifi ed a clinically aggressive molecular subtype.
DescriptionSession - Gynecologic and Obstetric Pathology: no. 1272
This free journal suppl. contain abstracts of USCAP 2014 Annual Meeting
Persistent Identifierhttp://hdl.handle.net/10722/211475
ISSN
2015 Impact Factor: 5.485
2015 SCImago Journal Rankings: 2.803

 

DC FieldValueLanguage
dc.contributor.authorSlatter, T-
dc.contributor.authorHsia, H-
dc.contributor.authorSamaranayaka, A-
dc.contributor.authorSykes, P-
dc.contributor.authorClow, W-
dc.contributor.authorDevenish, C-
dc.contributor.authorRoyds, J-
dc.contributor.authorIp, P-
dc.contributor.authorCheung, A-
dc.contributor.authorHung, N-
dc.date.accessioned2015-07-15T03:51:18Z-
dc.date.available2015-07-15T03:51:18Z-
dc.date.issued2014-
dc.identifier.citationThe 103rd Annual Meeting of the United States and Canadian Academy of Pathology (USCAP 2014), San Diego, CA., 1-7 March 2014. In Modern Pathology, 2014, v. 27 suppl. 2, p. 308A, abstract no. 1272-
dc.identifier.issn0893-3952-
dc.identifier.urihttp://hdl.handle.net/10722/211475-
dc.descriptionSession - Gynecologic and Obstetric Pathology: no. 1272-
dc.descriptionThis free journal suppl. contain abstracts of USCAP 2014 Annual Meeting-
dc.description.abstractBACKGROUND: Uterine smooth muscle tumors of uncertain malignant potential (STUMP) have variable pathological features and recurrence rates, which results in considerable treatment uncertainty. New prognostic markers are required. Alternative lengthening of telomeres (ALT) maintenance is associated with poor survival in some soft tissue leiomyosarcomas (LMS). ALT maintenance is related to mutations in ATRX (α-thalassemia/mental retardation syndrome X-linked) and DAXX (death-domainassociated protein) genes and their respective proteins are involved in remodelling of chromatin structure. ALT maintenance also produces extremely long protein structures ALT-associated PML bodies (APB). DESIGN: 40 LMS, 17 STUMPs, and 10 leiomyomas (LM) were studied and follow-up data obtained. They were screened for APBs by immunofl uorescent study (anti-PML, H-238, Santa Cruz). Telomere DNA was detected using a Cy3-labelled PNA probe (Life Technologies, Carlsbad). APB positive occur when when both PML protein and telomeric DNA are seen in the nucleus in≥ 0•5% of cells. Immunohistochemistry was done with ATRX and DAXX antibodies (respectively HPA001906 & HPA008736 Sigma-Aldrich, St Louis). Staining in <10% of nuclei were considered loss of expression. p53 (DO-7, Cell Marque) was also done. RESULTS: Mean patient ages and tumor sizes for LMS, STUMP and LM were respectively 49.5, 44.1 and 50.4 years, and 10, 8.5, and 3.5 cm. Recurrence/death was seen in 35% (6/17) STUMPs and 60% (24/40) LMS. No LMs recurred. For STUMPs, 24% (4/17) were APB+ve and 30% (5/17) overexpressed p53. Loss of staining for ATRX and DAXX was seen in 30% (5/17) and 12% (2/17), respectively. For LMS, 40% (16/40) were APB+ve and 42% (17/40) overexpressed p53. Loss of staining for ATRX and DAXX was seen in 58% (23/40) and 15% (6/40), respectively. All 6 STUMPs and 92% (22/24) LMS followed by recurrence/death showed loss of ATRX or DAXX expression. 60% (17/28) of these cases with adverse outcome were also APB positive. Overexpression of p53 (p=0.001) and loss of ATRX and/or DAXX expression (p<0.05) were associated with a poor outcome. CONCLUSIONS: Loss of ATRX or DAXX expression in uterine smooth muscle tumors identifi ed a clinically aggressive molecular subtype.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/modpathol/-
dc.relation.ispartofModern Pathology-
dc.subjectMedical sciences biology-
dc.titleLoss of ATRX and DAXX expression identifies poor prognosis for uterine smooth muscle tumors-
dc.typeConference_Paper-
dc.identifier.emailIp, P: philipip@hku.hk-
dc.identifier.emailCheung, A: anycheun@hkucc.hku.hk-
dc.identifier.authorityIp, P=rp01890-
dc.identifier.authorityCheung, A=rp00542-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/modpathol.2014.15-
dc.identifier.hkuros244975-
dc.identifier.volume27-
dc.identifier.issuesuppl. 2-
dc.identifier.spage308A, abstract no. 1272-
dc.identifier.epage308A, abstract no. 1272-
dc.publisher.placeUnited Kingdom-

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