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TP53 protein expression analysis by luminometric immunoassay in comparison with gene mutation status and prognostic factors in early stage endometrial cancer

Koul, Anjila LU ; Bendahl, Pär-Ola LU ; Borg, Åke LU ; Fernö, Mårten LU ; Lidebring, MF; Hogberg, T; Einarsson, EL; Ridderheim, Mona LU and Willen, R (2002) In International Journal of Gynecological Cancer 12(4). p.362-371
Abstract
Mutations in the TP53 tumor suppressor gene have been shown to significantly correlate with poor prognosis in endometrial cancer. In the present study we have evaluated a luminometric immunoassay (LIA) for quantitative estimation of TP53 protein expression in 65 cytosol preparations from endometrial cancer, previously analyzed for mutations in TP53 exons 4-10. LIA showed high (greater than or equal to 0.6 ng/mg protein) expression of TP53 protein in all eight tumors with missense mutation, but high protein levels were also detected in 15 tumors with normal TP53 sequence. All four tumors with nonsense or frameshift mutations had low or no TP53 protein expression. LIA was further evaluated in a retrospective study of 201 cytosol samples from... (More)
Mutations in the TP53 tumor suppressor gene have been shown to significantly correlate with poor prognosis in endometrial cancer. In the present study we have evaluated a luminometric immunoassay (LIA) for quantitative estimation of TP53 protein expression in 65 cytosol preparations from endometrial cancer, previously analyzed for mutations in TP53 exons 4-10. LIA showed high (greater than or equal to 0.6 ng/mg protein) expression of TP53 protein in all eight tumors with missense mutation, but high protein levels were also detected in 15 tumors with normal TP53 sequence. All four tumors with nonsense or frameshift mutations had low or no TP53 protein expression. LIA was further evaluated in a retrospective study of 201 cytosol samples from endometrial cancer. TP53 overexpression (>= 0.6 ng/mg protein) was observed in 22% of the tumors and correlated with nonendometrioid histology types (P = 0.005), poorly differentiated tumors (P = 0.001), higher FIGO grade (P = 0.001), DNA nondiploidy (P = 0.002), and high S-phase fraction (P = 0.03). After a median follow-up time of 6.8 years (range 0.7-9.9 years), 22 (13%) progressions were observed in the 175 patients with early stage (I-II) disease. TP53 overexpression (P = 0.04), FIGO grade 3 vs. 1 + 2 (P = 0.01), higher age (P = 0.02), and DNA nondiploidy (P < 0.001) showed significant correlation to shorter progression-free survival in these patients. We conclude that TP53 protein analysis by LIA provides an incomplete correlation to mutation status and cannot substitute for mutation analysis in assessment of prognosis in endometrial carcinoma. In comparison to TP53 overexpression and higher FIGO grades, DNA nonploidy status seems to be a better prognostic indicator to define a subset of early stage endometrial cancer patients who may benefit by adjuvant chemotherapy/radiotherapy. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mutation, DNA ploidy, endometrial cancer, TP53
in
International Journal of Gynecological Cancer
volume
12
issue
4
pages
362 - 371
publisher
Wiley-Blackwell
external identifiers
  • wos:000177085900007
  • scopus:0036326618
ISSN
1048-891X
DOI
10.1046/j.1525-1438.2002.01111.x
language
English
LU publication?
yes
id
d3b8af19-182f-47a4-8e2b-4a81a287d8c3 (old id 332707)
date added to LUP
2007-10-31 09:39:26
date last changed
2017-01-01 05:19:28
@article{d3b8af19-182f-47a4-8e2b-4a81a287d8c3,
  abstract     = {Mutations in the TP53 tumor suppressor gene have been shown to significantly correlate with poor prognosis in endometrial cancer. In the present study we have evaluated a luminometric immunoassay (LIA) for quantitative estimation of TP53 protein expression in 65 cytosol preparations from endometrial cancer, previously analyzed for mutations in TP53 exons 4-10. LIA showed high (greater than or equal to 0.6 ng/mg protein) expression of TP53 protein in all eight tumors with missense mutation, but high protein levels were also detected in 15 tumors with normal TP53 sequence. All four tumors with nonsense or frameshift mutations had low or no TP53 protein expression. LIA was further evaluated in a retrospective study of 201 cytosol samples from endometrial cancer. TP53 overexpression (&gt;= 0.6 ng/mg protein) was observed in 22% of the tumors and correlated with nonendometrioid histology types (P = 0.005), poorly differentiated tumors (P = 0.001), higher FIGO grade (P = 0.001), DNA nondiploidy (P = 0.002), and high S-phase fraction (P = 0.03). After a median follow-up time of 6.8 years (range 0.7-9.9 years), 22 (13%) progressions were observed in the 175 patients with early stage (I-II) disease. TP53 overexpression (P = 0.04), FIGO grade 3 vs. 1 + 2 (P = 0.01), higher age (P = 0.02), and DNA nondiploidy (P &lt; 0.001) showed significant correlation to shorter progression-free survival in these patients. We conclude that TP53 protein analysis by LIA provides an incomplete correlation to mutation status and cannot substitute for mutation analysis in assessment of prognosis in endometrial carcinoma. In comparison to TP53 overexpression and higher FIGO grades, DNA nonploidy status seems to be a better prognostic indicator to define a subset of early stage endometrial cancer patients who may benefit by adjuvant chemotherapy/radiotherapy.},
  author       = {Koul, Anjila and Bendahl, Pär-Ola and Borg, Åke and Fernö, Mårten and Lidebring, MF and Hogberg, T and Einarsson, EL and Ridderheim, Mona and Willen, R},
  issn         = {1048-891X},
  keyword      = {mutation,DNA ploidy,endometrial cancer,TP53},
  language     = {eng},
  number       = {4},
  pages        = {362--371},
  publisher    = {Wiley-Blackwell},
  series       = {International Journal of Gynecological Cancer},
  title        = {TP53 protein expression analysis by luminometric immunoassay in comparison with gene mutation status and prognostic factors in early stage endometrial cancer},
  url          = {http://dx.doi.org/10.1046/j.1525-1438.2002.01111.x},
  volume       = {12},
  year         = {2002},
}