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 neoplastic population, is unclear. Twenty-five cases of colorectal adenocarcinomas were investigated in parallel by immunocytochemical and hybridization (Northern blot) procedures to detect presence of three members 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 cells and expression of the related specific mRNA molecules. Interestingly, such discrepancies were more remarkable for Chromogranin A than for Chromogranin B and Secretogranin II. Taking into account all three types of chromogranins, only a few cases provided the same results at the mRNA and protein levels investigated respectively by Northern blot and immunohistochemistry. The spectrum of observed events is therefore wider and more complex than hitherto believed. Our interpretation is that transient activation of NE differentiation genes can be a common and 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 exocrine-endocrine patterns observed in carcinomas of different organs (gastrointestinal tract, pancreas, prostate, breast, lung).