TP53 overexpression in recurrent endometrial carcinoma.
OBJECTIVE
To study alterations within the p53 pathway in relation to the development of recurrent stage I endometrioid endometrial carcinoma.


METHODS
Paraffin-embedded tumor tissue of both primary and recurrent tumors from 44 patients with and 44 without recurrence was used for immunohistochemical analysis of TP53, hMdm2, P21(Waf1/Cip1) and M30. DNA was extracted, and mutation analysis of p53 (exon 5-8, 11) was performed by direct sequencing.


RESULTS
TP53 overexpression was significantly associated with recurrent disease: Odds Ratio 3.8 (95% CI: 1.5-9.8). Overexpression of TP53 was associated with lower staining indices (SI:0-9) of both hMdm2 and P21 in tumors of patients with recurrence, compared to controls: 2.0 +/- 0.4 vs. 4.0 +/- 0.8 and 1.9 +/- 0.8 vs. 3.6 +/- 0.8, respectively. Eight p53 missense mutations were identified in six patients with recurrence and two controls. One nonsense mutation was found in a patient with recurrence and one deletion in a control patient. Only a minority of TP53 overexpression cases could be explained by the presence of these p53 mutations.


CONCLUSIONS
TP53 overexpression was significantly predictive for recurrent endometrial carcinoma, and mostly not correlated with p53 mutations. Concomitant low hMdm2 and P21(Waf1/Cip1) expression in tumors with overexpressed TP53 suggests a dysfunctional TP53-P21(Waf1/Cip1) pathway.
Pijnenborg
Johanna M A
JM
Research Institute Growth and Development (GROW), Department of Obstetrics and Gynecology, University Hospital of Maastricht and University Maastricht, P.O. Box 5800, 6202 AZ Maastricht, Netherlands.
van de Broek
Leonie
L
Dam de Veen
Geeske C
GC
Roemen
Guido M J M
GM
de Haan
Jelte
J
van Engeland
Manon
M
Voncken
Jan Willem
JW
Groothuis
Patrick G
PG
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016612:Paraffin Embedding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007633:Keratins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2