title: TP53 protein expression analysis by luminometric immunoassay in comparison with gene mutation status and prognostic factors in early stage endometrial cancer.
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 (> or = 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.
authors.affiliation: Department of Oncology, Lund University Hospital, SE-221 85 Lund, Sweden. anjila.koul@onk.lu.se
authors.forename: Anjila
authors.initials: A
authors.lastname: Koul
authors.forename: P-O
authors.initials: PO
authors.lastname: Bendahl
authors.forename: A
authors.initials: A
authors.lastname: Borg
authors.forename: M
authors.initials: M
authors.lastname: Fernö
authors.forename: M F
authors.initials: MF
authors.lastname: Lidebring
authors.forename: T
authors.initials: T
authors.lastname: Högberg
authors.forename: E L
authors.initials: EL
authors.lastname: Einarsson
authors.forename: M
authors.initials: M
authors.lastname: Ridderheim
authors.forename: R
authors.initials: R
authors.lastname: Willén
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000401:mortality*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007118:Immunoassay; D008164:Luminescent Proteins; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D013548:Sweden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D008164:Luminescent Proteins; D016159:Tumor Suppressor Protein p53