Linked Life Data

9635683

Source:http://linkedlifedata.com/resource/pubmed/id/9635683

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1998-7-1
pubmed:abstractText
In contrast to endometrioid carcinoma, uterine papillary serous carcinoma (UPSC) is an aggressive type of endometrial cancer. Loss of p53 function is critical for the molecular pathogenesis of UPSC. Both UPSC and its putative precursor, endometrial intraepithelial carcinoma (EIC), show abnormal p53 overexpression in most tumors. To further assess the nature of p53 alterations in UPSC, we systematically reevaluated a subset of our previous cohort of UPSC patients. In the current study, we correlate mutations of the p53 gene as detected by direct sequencing of exons 5 through 8 with p53 accumulation and expression of Waf-1 in 32 UPSC tumors. Waf-1 is a downstream effector of p53-mediated G1 arrest after DNA damage and, thus, an indicator of p53 functionality. Although 78% of tumors exhibited strong nuclear p53 immunoreactivity in 100% of tumor cells, we were able to detect p53 mutations in 53%. As expected, all p53 mutant tumors (17 cases) exhibited p53 overexpression. Seventy percent of those (12 tumors) showed concomitant lack of Waf-1 expression consistent with transcriptionally inactive p53, whereas the other five tumors showed Waf-1 staining in only a minor fraction of tumor cells consistent with p53-independent Waf-1 expression. In contrast, 47% (15 cases) of tumors failed to exhibit p53 mutations; interestingly, more than half of those (eight cases) showed strong nuclear p53 accumulation in all tumor cells but lacked concomitant Waf-1 expression. These findings are consistent with a mutation-dependent and -independent type of p53 inactivation in UPSC that are both associated with nuclear overexpression. Our findings suggest that the combined immunocytochemical analysis of p53 and Waf-1 is a valuable means of assessing the functional status of p53. In summary, p53 alterations are common in UPSC and probably responsible for its aggressive biological behavior.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0046-8177
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
613-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Loss of p53 function in uterine papillary serous carcinoma.
pubmed:affiliation
Department of Pathology, University Hospital, State University of New York at Stony Brook 11794-8691, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't