| Summary: | Background: Colorectal cancer (CRC) is known to be affected by paraneoplastic thrombocytosis and chromogranin A-positive neuroendocrine-cell differentiation (CgA<sup>+</sup>). 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<sup>+</sup>. Results: Twenty-seven and 15 patients were assigned to the chromogranin A-negative (CgA<sup>−</sup>) and CgA<sup>+</sup> groups, respectively. Within the CgA<sup>+</sup> 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<sup>+</sup> group (<i>p</i> = 0.0086), thrombopoietin (<i>p</i> = 0.0040) and chromogranin B (<i>p</i> = 0.0070) in the CgA<sup>−</sup> group, while interleukin-6 was high in both tumor groups (<i>p</i> ≤ 0.0090). Survival was significantly worse in the CgA<sup>+</sup> group (hazard ratio: 5.73; <i>p</i> = 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.
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