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

Background: 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.

Methods: 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.

Results: 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 ( = 0.0086), thrombopoietin ( = 0.0040) and chromogranin B ( = 0.0070) in the CgA group, while interleukin-6 was high in both tumor groups ( ≤ 0.0090). Survival was significantly worse in the CgA group (hazard ratio: 5.73; = 0.0378).

Conclusions: 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.