Clonal analysis of esophageal squamous cell carcinoma with intraepithelial components.
OBJECTIVE
In tumors of the upper aerodigestive tract, field carcinogenesis is a prevailing concept which suggests that such tumors are commonly of multiclonal origin.


METHODS
To test this possibility, we applied a PCR-based clonality assay utilizing the polymorphic locus of the human androgen receptor gene (HUMARA) in female patients with esophageal squamous cell carcinomas (SCCs). DNA was extracted from small pieces of tissues microdissected from multiple points of intraepithelial and invasive parts of each tumor and the adjacent epithelia in 12 cases. The HUMARA locus was PCR amplified with or without prior digestion with Hpa II. PCR products were analyzed by a genetic analyzer and polyacrylamide gel electrophoresis followed by silver staining.


RESULTS
In each of 8 informative cases, the pattern of X chromosome inactivation of the major cell population in each sample was common among the samples from the invasive part and among those samples, if any, from the intraepithelial part, and was concordant between the intraepithelial and invasive parts in 5 cases and discordant in 1 case. Out of the samples of adjacent epithelia, a monoclonal pattern was demonstrated in 8 basal cell hyperplasias and 3 dysplasias, of which 2 and 1, respectively, showed inactivation patterns discordant with those of the concomitant cancers.


CONCLUSIONS
Esophageal SCCs may often be preceded or accompanied by multiclonal precancerous lesions, and may develop through the outgrowth of single or less commonly multiple dominant clones.
D000368:Aged; D002278:Carcinoma in Situ / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D002999:Clone Cells / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D004210:Dissection; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D006801:Humans; D008846:Micromanipulation; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics
C410798:AR protein, human; D004273:DNA, Neoplasm; D005819:Genetic Markers; D011944:Receptors, Androgen