An allelotype analysis indicating the presence of two distinct ovarian clear-cell carcinogenic pathways: endometriosis-associated pathway vs. clear-cell adenofibroma-associated pathway |
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Authors: | Sohei Yamamoto Hitoshi Tsuda Kozue Suzuki Masashi Takano Seiichi Tamai and Osamu Matsubara |
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Institution: | (1) Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan;(2) Department of Obstetrics and Gynecology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan;(3) Department of Laboratory Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan;(4) Pathology Section, Clinical Laboratory Division, National Cancer Center Hospital, Tokyo 104-0045, Japan; |
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Abstract: | Patterns of allele loss (loss of heterozygosity (LOH)) were studied to identify the genetic backgrounds underlying the two
putative carcinogenic pathways of ovarian clear-cell adenocarcinoma: carcinomas thought to arise in endometriosis (endometriosis-associated
carcinomas, 20 cases) and carcinomas thought to be derived from clear-cell adenofibroma ((CCAF)-associated carcinomas, 14
cases). Each tumor was assessed for LOH at 24 polymorphic loci located on 12 chromosomal arms: 1p, 3p, 5q, 8p, 9p, 10q, 11q,
13q, 17p, 17q, 19p, and 22q. For all informative loci, the frequency of LOH was not statistically different between the two
carcinoma groups: 38% (66/172 loci) in the endometriosis-associated carcinomas and 35% (40/113 loci) in the CCAF-associated
carcinomas. In the endometriosis-associated carcinomas, LOH was detected at high frequencies (>50%) at 3p, 5q, and 11q and
at low frequencies (<20%) at 8p, 13q, and 17p. In the CCAF-associated carcinomas, LOH was detected at high frequencies at
1p, 10q, and 13q and at low frequencies at 3p, 9p, 11q, and 17q. The frequencies of LOH at chromosomes 3p, 5q, and 11q were
significantly higher in the endometriosis-associated carcinomas than in the CCAF-associated carcinomas (P = 0.026, 0.007, and 0.011, respectively). Immunohistochemical analysis demonstrated a close association between the allelic
status of the 3p25–26 locus and levels of von Hippel–Lindau (VHL) protein expression (P = 0.0026). These data further support the presence of two distinct carcinogenic pathways to ovarian clear-cell adenocarcinoma;
the allelic status of the 3p, 5q, and 11q loci may provide a means to identify the precursor lesions of these carcinomas. |
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