Histopathological Chromogranin A-Positivity Is Associated with Right-Sided Colorectal Cancers and Worse Prognosis

Colorectal cancer (CRC) is known to be affected by paraneoplastic thrombocytosis and chromogranin A-positive neuroendocrine-cell differentiation (CgA⁺). Their combined effect has never been previously investigated.

A prospective cohort pilot study of 42 CRC patients and 42 age- and sex-matched controls was carried out. Plasma interleukin-6, thrombopoietin, and serum chromogranin A and -B were measured; furthermore, tumor tissue was immunohistochemically stained for CgA⁺.

Twenty-seven and 15 patients were assigned to the chromogranin A-negative (CgA^-) and CgA⁺ groups, respectively. Within the CgA⁺ group, right-sided tumors were more frequent (18.5% vs. 53.3%), no stage I cancer was found, and patients of this group were in worse general condition. Compared to control subjects, chromogranin A level was higher in the CgA⁺ group (p = 0.0086), thrombopoietin (p = 0.0040) and chromogranin B (p = 0.0070) in the CgA^- group, while interleukin-6 was high in both tumor groups (p ≤ 0.0090). Survival was significantly worse in the CgA⁺ group (hazard ratio: 5.73; p = 0.0378).

Different thrombopoietin levels indicated distinct thrombocytosis types. Within the two CRC groups, serum levels of chromogranins changed in different directions suggesting two well-distinguishable pathophysiologies. Based on these observations we propose a new subtype of CRC, which can be characterized by chromogranin A-positive neuroendocrine-cell differentiation.