Endometrial carcinomas are classified by their morphology into two major subtypes.
Endometrioid carcinomas (type I) are generally
estrogen dependent, well-differentiated, superficially invasive, and have a good outcome. Serous
carcinomas (type II) are
hormone independent, frequently deeply invasive and widely metastatic, and have a poor prognosis. Microarray technology and analysis allows us to determine if the global gene expression profiles of these two subtypes correlate with their morphologic phenotype. Fresh tissue from 18
endometrial carcinomas was studied: 7 well-, 2 moderately, and one poorly differentiated endometrioid, 4 serous
carcinomas, and 4 high-grade mixed endometrioid-serous
carcinomas. Labeled
cDNA probes were synthesized (
Cy5 for
tumor, Cy3 for reference) and applied to microarrays containing 18,098
cDNA clones or ESTs. A pool of equal amounts of total
RNA from each
tumor served as the reference
RNA. By unsupervised cluster analysis, the
endometrioid carcinomas clustered together and were separate from the serous
carcinomas. The high-grade mixed
carcinomas clustered with the serous
carcinomas. Using a statistical algorithm based on gene expression pattern and conducting a supervised analysis of the two defined groups, we have identified 315 genes that statistically differentiate type I from type II
endometrial carcinomas. In addition to corroborating the predicted overexpression of known markers (e.g., ras and
catenin in
endometrioid carcinomas), the
cDNA microarray technique has revealed novel alterations in gene expression relevant to cell cycle, cell adhesion, signal transduction, apoptosis, and
tumor progression not previously implicated in
endometrial carcinomas. For serous
carcinomas, these include
aldolase,
desmoplakin,
integrin-linked kinase, PKC, and
metallopeptidase. In conclusion, the gene expression profiles of type I and type II
endometrial carcinomas are different. Refinement of these profiles will permit more accurate diagnostic
tumor classification and the development of prognosis assays.