Gene expression profiling of endometrial adenocarcinomas reveals increased apolipoprotein E expression in poorly differentiated tumors.
BACKGROUND
Tumor grade is one of the most important prognostic factors in endometrioid endometrial adenocarcinoma. Amplification of oncogenes, such as Her2/neu, or loss of function of tumor suppressor genes, such as p53, are known to be associated with poor prognosis, but additional factors influencing clinical behavior are likely to exist. To examine the biological differences between low-grade and high-grade endometrioid endometrial adenocarcinomas, we compared gene expression in these 2 types of tumors.


METHODS
Six well-differentiated adenocarcinomas and 7 poorly differentiated adenocarcinomas were studied with 2 different microarray platforms, Affymetrix and Illumina. The expression of the most differentially expressed gene on both platforms was further studied in 34 endometrial adenocarcinoma samples (10 well differentiated, 9 moderately differentiated, and 15 poorly differentiated) using real-time reverse transcription-polymerase chain reaction.


RESULTS
The most differentially expressed gene on both platforms was Apolipoprotein E (APOE). In the poorly differentiated adenocarcinomas, APOE was overexpressed 13.1-fold (P = 0.001) and 9.7-fold (P = 0.007) when compared with well- and moderately differentiated tumors, respectively. There was no difference in APOE expression between well- and moderately differentiated adenocarcinomas.


CONCLUSIONS
Increased expression of APOE might represent a late event in the progression of well-differentiated endometrioid endometrial adenocarcinoma to a poorly differentiated endometrioid endometrial adenocarcinoma. Although increased APOE expression has been previously reported in other malignancies, this is the first study to suggest that APOE might also have a role in endometrioid endometrial cancer.
Huvila
Jutta
J
Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland.
Brandt
Annika
A
Rojas
Clarissa Rios
CR
Pasanen
Salla
S
Talve
Lauri
L
Hirsimäki
Pirkko
P
Fey
Vidal
V
Kytömäki
Leena
L
Saukko
Pekka
P
Carpén
Olli
O
Soini
Juhani T
JT
Grénman
Seija
S
Auranen
Annika
A
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling / Q000295:instrumentation / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation / Q000379:methods
D001057:Apolipoproteins E