Colorectal poorly differentiated neuroendocrine carcinomas and mixed adenoneuroendocrine carcinomas: insights into the diagnostic immunophenotype, assessment of methylation profile, and search for prognostic markers.

Colorectal poorly differentiated neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas
(MANECs) are well-recognized entities generally known to be
associated with biological aggressiveness and poor patient survival. However, a few published papers have highlighted the existence of a subgroup of tumors with a better survival than expected; however, to date, there are no established parameters that usefully identify this category. In the present study we have
investigated the morphologic features, the CpG methylator
phenotype (CIMP), microsatellite instability (MSI), and the
immunohistochemical profile, including the expression of transcription factors (TTF1, ASH1, CDX2, and PAX5), stem cell markers (CD117 and CD34), and cytokeratins 7 and 20, in a series of 39 carcinomas (27 NECs and 12 MANECs) to better characterize such neoplasms and to search for prognostic indicators. No different patient survival was observed between NECs and MANECs. Neoplasms showed a heterogenous spectrum of morphologic and immunohistochemical features;
however, only large-cell subtype, significant peritumoral lymphoid
reaction, CD117 immunoreactivity, vascular invasion, and MSI/CIMP+ status were significantly correlated with prognosis on univariable analysis. Furthermore, vascular invasion
and CD117 immunoreactivity were independent prognostic
markers on multivariable analysis. In addition to these
prognostic features, neoplasms showed different expression of transcription factors, stem cell markers, and cytokeratins that
should be considered for diagnostic purposes and, especially, for discriminating among possible differential diagnoses