CHROMOGRANIN GENE EXPRESSIONS IN COLORECTAL ADENOCARCINOMAS

Presence of neuroendocrine (NE) cells (identified by argyrophilia and presence of NE markers, such as the chromogranins) is a common event ( 15 to 51% of the cases) in colorectal adenocarcinomas. The nature and significance of these cells, scattered in variable number within the n eoplastic population, is unclear. Twenty-five cases of colorectal aden ocarcinomas were investigated in parallel by immunocytochemical and hy bridization (Northern blot) procedures to detect presence of three mem bers of the chromogranin family, i.e., Chromogranin A, Chromogranin B, and Secretogranin II/secretoneurin and their synthetic machinery. The results indicate discrepancies between presence of immunoreactive cel ls and expression of the related specific mRNA molecules. Interestingl y such discrepancies were more remarkable for Chromogranin A than for Chromogranin B and Secretogranin II. Taking into account all three typ es of chromogranins, only a few cases provided the same results at the mRNA and protein levels investigated respectively by Northern blot an d immunohistochemistry. The spectrum of observed events is therefore w ider and more complex than hitherto believed. Our interpretation is th at transient activation of NE differentiation genes can be a common an d extensive event in neoplastic stem cells. In a few postmitotic cells , expression of NE genes would lead to cytoplasmic accumulation of NE markers and regulatory peptides, retained even after the switching off of the genes. This hypothesis might be valid for various mixed exocri ne-endocrine patterns observed in carcinomas of different organs (gast rointestinal tract, pancreas, prostate, breast, lung).