Loss of heterozygosity in P53, BRCA1, and estrogen receptor genes and correlation to expression of p53 protein in ovarian epithelial tumors of different cell types and biological behavior.
Loss of heterozygosity (LOH) of tumor suppressor genes (TSGs) in ovarian epithelial tumors of differing cell types and biological behavior has not been thoroughly investigated. Moreover, there have been conflicting reports correlating LOH of the p53 gene to overexpression of p53 protein. This study evaluated 34 formalin-fixed, paraffin-embedded ovarian epithelial tumors for LOH by polymerase chain reaction (PCR) for the following microsatellite markers: TP53(17p13.1/p53 gene), D17S579(17q/BRCA1 gene), and ESR (6q24-27/estrogen receptor gene). LOH of the TP53 marker was detected in 4 (44%) of 9 informative serous cystadenocarcinomas (SCa) but in 0 of 4 informative clear cell carcinomas (CCa) and 0 of 5 informative serous tumors of low malignant potential (SLMP). LOH of the BRCA1 marker was detected in 5 (83%) of 6 informative SCa, but in 1 (13%) of 8 informative CCa and 1 (14%) of 7 informative SLMP. LOH of the ESR marker was detected in 4 (50%) of 8 informative SCa, but in 0 of 4 informative CCa and 1 (16%) of 6 informative SLMP. p53 protein overexpression was present in 8 of 12 SCa but did not correlate to TP53 LOH. LOH for TP53, D17S579/ BRCA1, and ESR is common in ovarian SCa, and is observed in primary tumors as well as metastases. In contrast, these genetic alterations are less common in CCa and in the biologically less aggressive SLMP tumors. These data suggest different mechanisms of oncogenesis in ovarian epithelial tumors of different cell types and biological behavior.
Otis
C N
CN
Department of Pathology, Baystate Medical Center, Tufts University School of Medicine, Springfield, MA 01199, USA.
Krebs
P A
PA
Quezado
M M
MM
Albuquerque
A
A
Bryant
B
B
San Juan
X
X
Kleiner
D
D
Sobel
M E
ME
Merino
M J
MJ
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics; D005260:Female; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics*
D019313:BRCA1 Protein; D011960:Receptors, Estrogen