Biomarker conservation in primary and metastatic epithelial ovarian cancer.
OBJECTIVE
The aim of this study was to compare the overexpression of specific biomarkers in primary advanced and recurrent epithelial ovarian cancers.


METHODS
Biomarker expression by epithelial ovarian cancer specimens from primary and metastatic sites was examined by immunohistochemistry and flow cytometry. Biomarker expression by subpopulations of tissues consisting of matched pairs of synchronous and metachronous lesions was also studied.


RESULTS
A total of 3173 epithelial ovarian cancer specimens were retrieved from women with FIGO Stage III/IV disease. These included lesions from 1036 primary and 2137 metastatic sites. The percentages of biomarker expression for primary and metastatic lesions, respectively, were MDR1, 12 and 10%; p53, 55 and 60%; HER2, 12 and 11%; EGF-R, 26 and 33%; increased microvessel counts (CD31), 21 and 36%. Approximately 73% of both primary and metastatic specimens were aneuploid, and approximately 57% of both sets had an S-phase fraction >7%. Only EGF-R and CD31 expression were found to be significantly different between the primary and metastatic tumors (P < 0.05). Of the paired synchronous cases (n = 48) evaluated, 88% of aneuploid primary lesions were associated with aneuploid metastases. Similarly, the distributions for MDR1, HER2, and p53 expression did not vary significantly between primary and metastatic sites. Pairings of metachronous cases (n = 66) revealed that nearly 80% of primary aneuploid tumors (n = 39) retained their aneuploid status at the time of relapse. Furthermore, there were no significant changes in MDR1, p53, or HER2 expression at relapse.


CONCLUSIONS
With the exception of EGF-R and CD31, clonal divergence of the biomarkers evaluated in this study probably does not play a significant role in imparting clinical heterogeneity during the advanced and recurrent stages of epithelial ovarian cancer. These particular genes likely undergo alterations early in the tumorigenesis process before metastases have become established.
Tewari
K S
KS
Section of Hematology & Oncology, Division of Gynecologic Oncology, The Chao Family Comprehensive Cancer Center, University of California, 101 The City Drive, Orange, California 92868, USA.
Kyshtoobayeva
A S
AS
Mehta
R S
RS
Yu
I R
IR
Burger
R A
RA
DiSaia
P J
PJ
Fruehauf
J P
JP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000378:metabolism; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D011003:Ploidies; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D066246:ErbB Receptors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53