Super-ISH™：Albumin mRNA in-situ Hybridization Assists in the Diagnosis of Hepatocellular Carcinoma

Current Status of Liver Cancer Diagnosis

Tumors metastasizing to the liver from other organs: The liver is the largest solid organ in the human body and is the most common site of metastasis for most malignant tumors, especially gastrointestinal and pancreatic malignancies.

Hepatocellular carcinoma (HCC) is a primary concern due to its potential for extrahepatic metastasis. It has been observed that approximately 10% of HCC cases are accompanied by metastasis to other organs at the time of initial diagnosis. The most common sites of extrahepatic metastasis include the lungs, lymph nodes, bones, and adrenal glands. This highlights the importance of not only differentiating HCC from primary liver tumors, such as intrahepatic cholangiocarcinoma and biphenotypic hepatocellular carcinoma, but also distinguishing it from various malignant tumors with similar histological features outside the liver.

However, the existing markers used in pathological diagnosis, such as hepatocyte paraffin antigen (HepPar-1) and arginase-1 (Arg-1), have limitations in poorly differentiated HCC. These markers exhibit low positivity rates in poorly differentiated HCC, making the differential diagnosis of this subtype particularly challenging. This emphasizes the need for improved markers and diagnostic techniques that can accurately identify and differentiate poorly differentiated HCC from other malignancies.

The potential for extrahepatic metastasis in HCC necessitates a comprehensive approach to its diagnosis, considering both primary liver tumors and other malignant tumors with similar histological features. The development of more effective markers and diagnostic methods is crucial for improving the accuracy of HCC diagnosis, especially in cases of poorly differentiated HCC.

Albumin mRNA – Liver Cell-Specific Marker

Albumin is a water-soluble protein secreted by liver cells. After synthesis in the liver, it is released into the bloodstream and is responsible for transporting hormones, fatty acids, and regulating pH, among other biological functions.

Previous studies have shown that the detection of albumin within tumor cells in the liver can effectively determine whether the tumor cells originate from hepatocytes. In clinical pathological testing, it is often necessary to differentiate primary liver cancer. The detection of albumin can help determine whether the tumor cells in liver lesions and extrahepatic metastases originate from hepatocytes. 

Is Immunohistochemistry Feasible for Detection?

Due to the fact that albumin is a secreted protein, there are certain issues with using immunohistochemistry to track albumin (ALB) at the protein level:

Conventional immunohistochemistry methods face challenges when detecting albumin due to the presence of albumin in the serum, which can cause excessive background staining and make the results difficult to interpret. Additionally, damaged cells can absorb albumin from the serum, leading to false-positive results. However, an alternative approach using RNA in situ hybridization can overcome these limitations. Since the messenger RNA (mRNA) encoding albumin is retained within the cells, RNA in situ hybridization allows for the specific detection of target RNA molecules. This makes RNA in situ hybridization an ideal method for accurately detecting albumin expression, providing more reliable and interpretable results.

Progress in domestic and international research

In recent studies conducted by various research institutions abroad, in situ hybridization technology has been utilized to detect the mRNA of Albumin. The objective of these studies was to analyze the role of albumin mRNA in the differential diagnosis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. The results obtained from these studies have shown promising outcomes. It has been found that using in situ hybridization to detect albumin mRNA is not only effective in detecting hepatocellular carcinoma but also demonstrates good detection efficacy for intrahepatic cholangiocarcinoma. This innovative approach aids in the identification of cancer cells originating from hepatocytes and facilitates the differentiation of these cells from metastatic tumors located outside the liver. The utilization of in situ hybridization technology for albumin mRNA detection holds significant potential in improving the accuracy of pathological diagnosis for these types of liver tumors.

The Pathology Department of Ruijin Hospital affiliated with Shanghai Jiao Tong University in China conducted a study published in the Chinese Journal of Pathology in 2022, focusing on the role of albumin in situ hybridization in the diagnosis and differential diagnosis of liver cancer. The study aimed to compare the sensitivity of albumin in situ hybridization with that of HepPar-1 and Arg-1 antibodies in diagnosing hepatocellular carcinoma. The results revealed that the sensitivity of HepPar-1 and Arg-1 antibodies, whether used alone or in combination, was lower compared to albumin in situ hybridization. Notably, when both HepPar-1 and Arg-1 were negative, albumin in situ hybridization demonstrated significant value in the diagnosis of hepatocellular carcinoma. This suggests that albumin in situ hybridization can serve as a valuable tool in accurately diagnosing hepatocellular carcinoma, particularly in cases where traditional antibody markers yield negative results.

Celnovte Super-ISH™ Albumin ISH

Celnovte Biotech, established in 2010, is a high-tech enterprise specializing in the research, development, production, and sales of precision diagnostic instruments and reagents for tumors. With a focus on early screening, precise diagnosis, drug companion, and treatment monitoring of tumors, Celnovte Biotech aims to provide comprehensive solutions for tumor pathology diagnosis products. The company has a complete solution for immunohistochemistry, offering a wide range of primary antibodies, secondary antibody detection systems, immunohistochemistry quality control products, and fully automated staining platforms. Committed to quality, innovation, and service, Celnovte Biotech strives to be a leading provider of top-notch products and services in the industry, contributing to scientific and technological innovation in the field of life sciences and medicine in China.

Celnovte Biotech has developed the Super-ISH™ technology platform, which is an advanced in situ hybridization technique used to detect mRNA in cells. This innovative technology enables the sensitive and specific detection of single-cell, single-molecule mRNA expression, including various modifications such as m1A, m6A, m6Am, m3C, m5C, hm5C, Nm, and pseudouridine (Ψ), in paraffin-embedded tissues. The Super-ISH™ technology is not limited to human samples but can also be applied to various animal model samples.

One of the key advantages of the Super-ISH™ technology is its ability to combine with immunohistochemistry detection technology. This allows for the simultaneous detection of multiple targets on the same tissue section, providing researchers with more comprehensive information for tissue microenvironment analysis. By utilizing this technology, Celnovte Biotech offers new possibilities for studying gene expression patterns and understanding the intricate molecular mechanisms underlying various diseases, including cancer. The Super-ISH™ technology platform represents a significant advancement in the field of in situ hybridization, providing researchers and clinicians with a powerful tool for studying mRNA expression in tissues. Its sensitivity, specificity, and ability to detect modifications make it a valuable asset in the field of molecular pathology and tissue analysis.

Celnovte Biotech has utilized the Super-ISH™ technology platform to develop a detection product for Albumin mRNA in-situ hybridization. This innovative product enables the sensitive and specific detection of Albumin mRNA expression in FFPE tissues. By accurately detecting Albumin mRNA, it assists in the precise pathological diagnosis of hepatocellular carcinoma. In addition to the Albumin mRNA detection product, Celnovte Biotech also provides efficient solutions like Kappa/Lambda Probe Kit (ISH) and EBER/IHC Dual Staining Kit for detection and diagnosis. These comprehensive solutions cater to the diverse needs of researchers and clinicians in the field of molecular pathology.