Loss of heterozygosity in usual and special variant carcinomas of the endometrium.
Endometrial carcinoma is the most common invasive malignancy of the female genital tract, and it exists as two different clinicopathologic forms: an estrogen-dependent, "usual" type and an estrogen-independent "special variant" type. Despite the frequency of endometrial cancer, little is known about the molecular genetic events that contribute to its pathogenesis. The accumulation of genetic alterations identified through the study of loss of heterozygosity (LOH), gene mutation, and gene activation in tumor DNA has been associated with the establishment and progression of a variety of human malignancies. A relatively low incidence of LOH has been reported in usual type endometrial cancers; however, special variant tumors have rarely been included in the reported studies. To understand the molecular events that contribute to both forms of endometrial cancer, 31 tumors have been surveyed for events of LOH on all chromosomes. The study groups included 18 tumors of the usual type and 13 special variant tumors. Polymorphic loci were studied by Southern blot analysis and polymerase chain reaction (PCR) of microsatellite loci. Normal tissue in each case served as a control. Both frequency and patterns of LOH differed greatly between the two tumor types. Although LOH was frequently detected in the special variant tumors, it was rare in the usual type tumors. LOH was detected in only 8 of the 18 usual tumors, with chromosomes 17, 13, and 2 being the most frequently affected (22%, 20%, and 19%, respectively). In contrast, LOH was detected in all cases of special variant tumors, with chromosomes 17p, 14, and 12 showing the highest LOH (83%, 77%, and 40%, respectively). Two cases of microsatellite instability (MI) were detected among the usual type tumors. These findings suggest that the clinicopathologic phenotypes observed in these tumor types are likely caused by different tumorigenic pathways that reflect alterations of different cancer-controlling genes.
Tritz
D
D
Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, USA.
Pieretti
M
M
Turner
S
S
Powell
D
D
D015139:Blotting, Southern; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000032:analysis*; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006579:Heterozygote; D006801:Humans; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm