DETECTION OF CHROMOGRANIN-A MESSENGER-RNA IN SMALL-CELL LUNG-CARCINOMA USING A NEW, HIGHLY SENSITIVE IN-SITU HYBRIDIZATION METHOD WITH A NON-RADIOISOTOPE OLIGONUCLEOTIDE PROBE

BACKGROUND. Immunoreactivity for chromogranin A (Cg A) is associated w ith the presence of neurosecretory granules in tumor cells, but immuno histochemical staining for Cg A may be absent in small cell lung carci noma (SCLC), which has only a few secretory granules. Localization of Cg A mRNA is a useful indicator of the site of synthesis of a particul ar 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-radiois otope (RI) oligonucleotide probe. METHODS. The authors analyzed Cg A m RNA in 20 cases of SCLC in formalin fixed, paraffin embedded tissue us ing a new, highly sensitive in situ hybridization method that was deve loped 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 rea ction for Cg mRNA. No NSCLC specimens showed any positive reaction for Cg A mRNA. CONCLUSIONS. The detection of Cg A mRNA using the new, hig hly sensitive in situ hybridization method with a non-RI oligonucleoti de probe can be used to characterize neuroendocrine differentiation of lung tumors even when the Cg A protein is not detected by immunohisto chemistry. The authors believe this is a first step toward better diag nosis and treatment for patients with SCLC. (C) 1998 American Cancer S ociety.