LOSS OF TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR GENE-EXPRESSION IN PRIMARY HUMAN ESOPHAGEAL CANCER

Cell lines derived from carcinomas of the upper aero-digestive tract a re typically refractory to transforming growth factor beta-mediated ce ll cycle arrest. Recently, we reported that the type Il transforming g rowth factor beta receptor (T beta R-II) gene can be inactivated on th e basis of missense mutations in such cell lines. These findings promp ted us to investigate the molecular status of the T beta R-II gene in primary tumor specimens. Among 21 of 24 evaluable primary esophageal c arcinomas, there were 6 cases (28.5%; 95% confidence interval, 11% to 52%) in which T beta R-II transcripts were low or undetectable by a re verse transcription PCR assay. In one of these cases, we were able to ascribe the loss of T beta R-II gene expression to high-density methyl ation of promoter sequences. We failed to detect any mutations within the open reading frame of the remaining tumors that expressed T beta R -II mRNA. in this relatively small series of cases, loss of T beta R-I I expression was independent of pathologic tumor stage, histologic sub type, or outcome of patients with esophageal cancer. Thus, loss of exp ression of the T beta R-II gene appears to be the predominant mechanis m through which this gene is inactivated in esophageal cancer.