Loss of heterozygosity among tumor suppressor genes in invasive and in situ carcinoma of the uterine cervix.
The aim of the present study was to further clarify the histogenesis of cervical carcinoma by investigating loss of heterozygosity (LOH) among a number of tumor suppressor genes in invasive and in situ carcinoma of the cervix. Materials consisted of 16 in situ and 29 invasive carcinomas (16 squamous cell carcinomas, nine adenocarcinomas, and four adenosquamous carcinomas). DNA samples were collected by microdissection from ordinary formalin-fixed, paraffin-embedded tissues, both from the lesions and from normal tissues. LOH was analyzed using eight DNA polymorphic tumor suppressor markers. Of the 16 cases of carcinoma in situ, three cases exhibited LOH at one locus. Of the 29 cases of invasive carcinomas, six cases exhibited LOH at two loci and nine cases exhibited LOH at one locus. Overall, LOH was found more frequently in invasive carcinomas than in in situ carcinomas. LOH was most frequently detected at the PTCH (Drosophila patched gene) locus. There was no significant correlation between LOH at a specific site and either histologic subtype or clinical stage. These results suggest that LOH might already occur in a fraction of preinvasive squamous lesions and that accumulation of LOH may in part play a role in carcinogenesis of the cervix.
Departments of Obstetrics & Gynecology, and Organ Regeneration, Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University School of Medicine, Matsumoto, and Department of Gynecology and Obstetrics, Kyoto University Faculty of Medicine, Kyoto, Japan.
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Lu
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Nikaido
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Toki
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Zhai
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Kita
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Konishi
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Fujii