Cells with distinct phenotypes including stem-cell-like properties have been proposed to exist in normal human mammary epithelium and breast carcinomas, but their detailed molecular characteristics and clinical significance are unclear. We determined gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem-cell-like properties. CD24+ and CD44+ cells from individual tumors were clonally related but not always identical. CD44+ cell-specific genes included many known stem-cell markers and correlated with decreased patient survival. The TGF-beta pathway was specifically active in CD44+ cancer cells, where its inhibition induced a more epithelial phenotype. Our data suggest prognostic relevance of CD44+ cells and therapeutic targeting of distinct tumor cell populations.

The murine monoclonal antibody OC 125 reacts with an antigen (CA 125) common to most nonmucinous epithelial ovarian carcinomas. An assay has been developed to detect CA 125 in serum. By this assay, only 1 per cent of 888 apparently healthy persons and 6 per cent of 143 patients with nonmalignant disease had serum CA 125 levels above 35 U per milliliter. In contrast, 83 of 101 patients (82 per cent) with surgically demonstrated ovarian carcinoma had elevated levels of antigen. In 38 patients with epithelial ovarian carcinoma monitored on 2 to 18 occasions during 2 to 60 months, antigen levels ranged from less than 1 to more than 8000 U per milliliter. Rising or falling levels of CA 125 correlated with progression or regression of disease in 42 of 45 instances (93 per cent). Determination of CA 125 levels may aid in monitoring the response to treatment in patients with epithelial ovarian cancer.

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