Background: Immunoreactivity for chromogranin A (Cg A) is associated with the presence of neurosecretory granules in tumor cells, but immunohistochemical staining for Cg A may be absent in small cell lung carcinoma (SCLC), which has only a few secretory granules. Localization of Cg A mRNA is a useful indicator of the site of synthesis of a particular protein and possibly the rate of synthesis, and it is not dependent on posttranslation events within the cells. However, it is difficult to detect the low levels of mRNA copies using the standard non-radioisotope (RI) oligonucleotide probe.
Methods: The authors analyzed Cg A mRNA in 20 cases of SCLC in formalin fixed, paraffin embedded tissue using a new, highly sensitive in situ hybridization method that was developed from the maximized immunohistochemistry (ImmunoMax) method. They also investigated Cg A mRNA in nonsmall cell lung carcinoma (NSCLC), including ten cases each of adenocarcinoma and squamous cell carcinoma of the lung.
Results: All examined SCLC tissues showed a positive reaction for Cg mRNA. No NSCLC specimens showed any positive reaction for Cg A mRNA.
Conclusions: The detection of Cg A mRNA using the new, highly sensitive in situ hybridization method with a non-RI oligonucleotide probe can be used to characterize neuroendocrine differentiation of lung tumors even when the Cg A protein is not detected by immunohistochemistry. The authors believe this is a first step toward better diagnosis and treatment for patients with SCLC.