Independent Prognostic Biomarker Found for Klatskin Tumor Patients

Curative treatment of intrahepatic cholangiocarcinoma (ICC) and hilar cholangiocarcinoma (Klatskin tumors) is limited to surgical resection or orthotopic liver transplantation, however, not all patients benefit from a surgical approach and suffer from early tumor recurrence.

The earlier a cancer is detected, the greater the chances of successful treatment and a long survival time and therefore a blood test has been developed for early detection of cancer. With the blood test, it is possible, at a very early stage of cancer (colon cancer, gastric cancer, lung cancer) to identify patients who are at high risk of developing life-threatening metastases.

Scientists at the Max Delbrück Center for Molecular Medicine (Berlin, Germany) and their collaborators examined tissue samples from 156 patients with Klatskin and ICC carcinomas, from who between 1998 and 2003 a part of the liver was removed. Among them were 76 patients with Klatskin carcinomas. The tissue samples contained both malignant tissue as well as cancer-free tissue. Tissue samples from patients with benign liver diseases were also included.

Included in the study was metastasis-associated in colon cancer 1 (MACC1), a recently discovered regulator of the hepatocyte growth factor (HGF)/Met/mitogen-activated protein kinase pathway, which induces proliferation, migration, and invasion in cell culture, as well as metastasis. The team measured the expression of MACC1, Met, and HGF messenger ribonucleic acid (mRNA) in microdissected tumor tissue and corresponding normal liver tissue using real-time quantitative reverse-transcriptase polymerase chain reaction. They used immunohistochemical staining to validate the results.

The study showed that the MACC1 gene is expressed ten 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 two years (613 days) in contrast to six years (2257 days) for patients with low MACC1. The relapse-free time, i.e., the time without cancer recurrence, in patients with high MACC1 levels was just under two years. However, MACC1 proved unsuitable as a biomarker for intrahepatic cholangiocellular carcinoma (ICC).

Johann Pratschke, from the Charité Universitätsmedizin (Berlin, Germany) and a coauthor, said, “Patients with Klatskin tumors may also benefit from liver transplantation and may live longer, under the condition that they have a low risk of recurrence.” The test for the detection of MACC1 in tumors and in blood has been patented in the USA, Australia, Japan, Canada, and Europe. The study was published in the September 2015 issue of the journal Hepatology.

Related Links:
Max Delbrück Center for Molecular Medicine
Charité Universitätsmedizin