Bile duct cancer is rare and usually detected too late. Often only extensive liver surgery can help or, in rare cases, liver transplantation. But which patients will not benefit from surgery because their risk of cancer recurrence is too high? Using the oncogene MACC1 as a biomarker, physicians now have a tool to help them decide which treatment option is best for patients with Klatskin carcinoma, one type of bile duct cancer.

If MACC1 expression is low, the patient has a good chance that surgery will prolong survival. By contrast, if the gene is upregulated, the risk of recurrence is high. These findings were published in Hepatology (doi:10.1002/hep.27885). Andri Lederer and Professor Ulrike Stein, PhD, of the Experimental and Clinical Research Center (ECRC), an institutional cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and the Charité – Universitätsmedizin Berlin on Campus Berlin –Buch, in Germany, led the study.

The bile ducts are the drainage system for bile produced by the liver cells. There are bile ducts inside and outside the liver. The bile ducts of the right and left hepatic lobes join to form the common bile duct, which opens into the small intestine (duodenum). There, the bile is required for the digestion of fat.

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One type of bile duct cancer is Klatskin carcinoma, which develops just outside the liver. Another type is intrahepatic cholangiocarcinoma (ICC), which starts inside the liver. Both types of bile duct cancer are rare, only 1 in 100,000 people in Europe and the United States is affected. However, these bile duct cancers comprise the second most common malignancy of the liver after primary liver cell cancer.

Since both Klatskin tumors and ICC are usually detected too late, they are difficult to treat, and patients’ life expectancy is severely reduced. Approximately 30% of patients survive the first 5 years after liver surgery.

Using the MACC1 gene as biomarker, physicians can now determine the risk of metastasis in Klatskin carcinoma. Tissue samples from 156 patients with Klatskin and ICC carcinomas, 76 of whom had Klatskin carcinoma, were examined. MACC1 expression was 10 times higher in cancer tissue than in normal tissue.

Moreover, in recurrent tumors that developed in the patient after surgery, MACC1 expression was much higher than in normal tissue. The survival time of patients with high MACC1 levels amounted, on average, to a little less than 2 years (613 days) in contrast to 6 years (2,257 days) for patients with low MACC1. The relapse-free time, ie, the time without cancer recurrence, in patients with high MACC1 levels was just under 2 years (753 days) in contrast to almost 9 years (3,119 days) for patients with low MACC1 levels.

However, MACC1 proved unsuitable as a biomarker for intrahepatic cholangiocellular carcinoma (ICC).

The researchers also developed a blood test for early detection of cancer, based on the MACC1 gene. With the blood test, it is possible, at a very early stage of some cancers (colon, gastric, and lung) to identify patients who are at high risk of developing life-threatening metastases. Meanwhile, the test for the detection of MACC1 in tumors and in blood has been patented in the United States, Australia, Japan, Canada, and Europe.