Molecular mechanisms of DES-induced carcinogenesis ; risk assessment markers in the DES-exposed

Molecular genetic analysis of clear cell adenocarcinomas of the vagina and cervix associated and unassociated with diethylstilbestrol exposure in utero

1996 Study Abstract

BACKGROUND
Prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) is associated with the subsequent development of clear cell adenocarcinoma of the lower reproductive tract in young women, and data concerning the molecular genetic alterations involved in the etiology of this tumor type have not previously been reported.

Such knowledge would be of potential value by providing insight into the molecular mechanisms of hormonal carcinogenesis in general, as well as by suggesting molecular markers for risk assessment in the estrogen-exposed population.

METHODS
A total of 24 samples of clear cell adenocarcinoma of the vagina or cervix, 16 associated with exposure in utero to DES and 8 with no history of DES exposure, were obtained as archival fixed and embedded tissue specimens. DNA was purified from these tissues and used to examine a number of biologically plausible molecular genetic endpoints for tumor specific alterations.

RESULTS

  • No evidence was found for mutations in the K-ras or H-ras protooncogenes, the Wilms’ tumor (WT1) tumor suppressor gene, or the estrogen receptor gene.
  • Sporadic overexpression of the p53 tumor suppressor gene was detected in some tumor cell nuclei by immunohistochemistry, but in the absence of detectable p53 gene mutation.
  • Genetic instability as manifested by somatic mutation of microsatellite repeats was widespread in these tumors, with evidence of microsatellite instability in all DES-associated tumors examined, and in 50% of those tumors not associated with DES exposure.

CONCLUSIONS
These data are consistent with the hypothesis that the induction of genomic instability may be an important mechanism of DES-induced carcinogenesis.

  • Molecular genetic analysis of clear cell adenocarcinomas of the vagina and cervix associated and unassociated with diethylstilbestrol exposure in utero, Cancer, NCBI PubMed PMID : 8630958, 1996 Feb.
  • Featured image credit Mike Beauregard.
DES DIETHYLSTILBESTROL RESOURCES

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