Immunohistochemistry remains the go-to method in clinical settings for diagnosing neuroendocrine tumors (NETs), even over newer, state-of-the-art techniques such as next-generation sequencing (NGS). It is fast, cost-effective, and easy to interpret when standardized. This technique is essential for cancer diagnosis, as it allows visualization of key markers at the histologic level that can guide treatment decisions and even prompt genetic counseling for patients.
When diagnosing NETs on histologic slides, pathologists rely heavily on these markers, since tumor morphology alone is often insufficient. Traditional first-generation markers, such as chromogranin A (CGA) and synaptophysin (SYP), are still considered the gold standard. However, non-NET tumors can sometimes exhibit neuroendocrine differentiation, and some highly aggressive NETs may lose the ability to express these markers.
This is why second-generation markers like ISL1, INSM1, and SECG are valuable. They can improve diagnostic accuracy in challenging cases, help identify poorly differentiated neuroendocrine carcinomas that do not express CGA or SYP, and provide insights into the origins of metastatic tumors when the primary site is unknown.
In a recent study examining these markers across a wide range of NETs and non-NETs, researchers found that while ISL1, INSM1, and SECG demonstrated comparable ability to detect neuroendocrine differentiation, they were slightly less sensitive due to variability in protein expression across different tissue types.
Because these newer markers are less sensitive than traditional ones like CGA and SYP, they are likely present in lower concentrations in the blood. As a result, they may not be suitable for routine detection using common methods such as spectrophotometry or mass spectrometry.
However, Inter Science Institute uses a classic method called radioimmunoassay (RIA), an extremely sensitive and precise laboratory technique. RIAs utilize radioactively labeled molecules to quantify substances such as antigens or antibodies in a sample. By having labeled and unlabeled molecules compete for antibody binding, RIAs enable accurate concentration measurements. The detection of radioactive signals offers greater sensitivity than any other currently available method.
Xingqun Liang , Mi-Ryoung Song, ZengGuang Xu, Guillermo M Lanuza, Yali Liu, Tao Zhuang, Yihan Chen, Samuel L Pfaff, Sylvia M Evans, Yunfu Sun. Isl1 Is required for multiple aspects of motor neuron development. Molecular and Cellular Neuroscience Volume 47, Issue 3, July 2011, Pages 215-222.
Carl Christofer Juhlin. Second-Generation Neuroendocrine Immunohistochemical Markers: Reflections from Clinical Implementation. Biology (Basel). 2021 Sep 5;10(9):874. doi: 10.3390/biology10090874