RELATIONSHIP BETWEEN LOSS OF ESTROGEN AND PROGESTERONE-RECEPTOR EXPRESSION AND OF 6Q AND 11Q CHROMOSOME ARMS IN BREAST-CANCER

The expression of estrogen (ER) and progesterone (PR) receptors was quantified in a series of 95 cytogenetically characterized breast cancers. The relationship between deficiencies of 6q and 11q arms (where genes for ER and PR are mapped, respectively) and ER and PR expression was analyzed. The range of variations in expression was very large by comparison to that of the number of chromosome arms. Furthermore, low expression without chromosome loss and high expression with chromosome loss were occasionally observed. Thus, major variations in ER and PR expression were independent of the number of copies of the corresponding gene. However, both the decrease in ER expression and 6q arm losses were correlated with cytogenetic evolution of the tumors, this correlation being less significant for PR and the 11q arm. In addition, 6q- but not 11q- tumors have, on the average, a low ER/PR ratio, whereas 11q- but not 6q- tumors have a low PR/ER ratio. When all 6q- or 11q- tumors were compared to those with no 6q- or 11q- losses, the average ER or PR value of the former was about half of the later. These data suggest that, in addition to a regulatory change of non-genetic origin, gene dosage effect plays a secondary, but significant, additional role. (C) 1994 Wiley-Liss, Inc.