Br J Cancer: RNAscope technology to detect α-fetoprotein mRNA level is a new and highly specific marker for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, accounting for 70-90% of global primary liver cancers.
According to previous guidelines, the diagnosis of liver cancer ismainly based on non-invasive criteria and/or pathological diagnosis.
Although imaging techniques (including ultrasound, computed tomography, and magnetic resonance imaging techniques) are usually used in the diagnosis process, there are still uncertain lesions due to the lack of corresponding imaging features.

HCC includes highly differentiated and low-differentiated tumors, which also brings many challenges to the pathological diagnosis of the disease, especially in small biopsies.
However, the pathological diagnosis of HCC is still difficult to distinguish between benign and non-hepatocellular malignant lesions.
Alpha-fetoprotein (AFP) is a tumor-associated antigen with high specificity for primary liver cancer.
Therefore, this study aims to explore the potential role of AFP mRNA RNAscope in situ detection technology (a sensitive and specific method) in the diagnosis of liver cancer.

The researchers analyzed three independent retrospective cohorts that included 2216 patients with HCC, benign liver disease, and non-hepatocellular tumors.
Detect the level of AFP by ELISA, IHC ( immunohistochemistry ) and RNAscope technology, and use IHC to detect related proteins such as GPC3, HepPar-1 and Arg-1.

Related process diagram

The results show that compared to IHC, AFP RNAscope can increase the sensitivity of HCC detection by 24.
7–32.
7%.
In the two surgical cohorts, the AFP RNAscope and GPC3 groups provided the best diagnostic value in distinguishing HCC from benign hepatocellular lesions, while the other group containing AFP RNAscope, GPC3, HepPar-1 and Arg-1 showed The best diagnostic value for distinguishing HCC from non-hepatocellular malignancies.

Representative image of AFP RNAscope in HCC samples

Similarly, the results of the liver biopsy cohort were similar, and the application of AFP RNAscope also increased the sensitivity of distinguishing HCC from benign hepatocellular lesions by 18%.

All in all, the results of the study revealed that the level of AFP mRNA detected by RNAscope is highly specific for hepatocellular malignancies, and it may be used as a new diagnostic biomarker for HCC.