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Levels of three potential biological markers of ovarian cancer—CA125, human epididymis protein 4, and mesothelin—begin to rise three years before the clinical diagnosis of ovarian cancer, but only become substantially elevated less than a year before diagnosis. Detection of cancer at this stage may not be early enough to improve outcomes. These results were published in the Journal of the National Cancer Institute.

Mortality rates from ovarian cancer continue to be high, largely because many women are not diagnosed with the disease until it has reached an advanced stage. In an attempt to improve survival by detecting the disease at an earlier stage, researchers are evaluating potential biological markers of the disease. Levels of certain proteins in the blood, for example, may be higher in women with ovarian cancer than in women without ovarian cancer. If these markers reliably distinguish women with and without ovarian cancer, and if the markers can be identified early in cancer development (before the cancer would typically be diagnosed clinically), then they may contribute to the early detection of ovarian cancer.

The current study evaluated six potential biological markers of ovarian cancer: CA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy receptor 3 (DcR3), and spondin-2.[1] Levels of each were measured in serum samples taken from 34 women who were later diagnosed with ovarian cancer, and 70 women who remained free of ovarian cancer.

Levels of three of these markers—CA125, HE4, and mesothelin—began to increase slightly three years before the diagnosis of ovarian cancer. Levels didn’t become markedly elevated until the last year prior to diagnosis, however, and the overall ability of these markers to reliably identify women with ovarian cancer was limited.

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Although the results of this study suggest that these particular markers may do little to increase early detection of ovarian cancer, this type of research continues to hold promise. An accompanying editorial notes that these results “are not the last word in serum markers or in combinations of markers. Serum markers likely will form a key element in any screening regimen…”[2]


[1] Anderson GL, McIntosh M, Wu L et al. Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study. Journal of the National Cancer Institute. 2010;102:26-38.

[2] Hartge P. Designing early detection programs for ovarian cancer. Journal of the National Cancer Institute. 2010;102:3-4.

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