Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11740
Peer-review started: April 30, 2015
First decision: June 23, 2015
Revised: July 7, 2015
Accepted: September 15, 2015
Article in press: September 15, 2015
Published online: November 7, 2015
Neuroendocrine differentiation in sporadic colorectal cancer has been recognized since decades, but its clinical impact is still controversially discussed. Detailed parameter analyses hint at the possibility that probably not neuroendocrine differentiation itself, but its association with poor grade of tumor differentiation, lymph node metastases, distant metastases and other unfavorable features contribute to worse clinical outcome. However, other studies deny a relationship between neuroendocrine differentiation and prognosis of colorectal cancer. This review elucidates, whether new insights into the origin of neuroendocrine differentiation in the intestinal epithelium, its regulation by mTOR pathway components and its possible link to the intestinal stem cell compartment could determine a role of neuroendocrine cells as prognostic marker and putative therapeutic target in sporadic colorectal cancer.
Core tip: Neuroendocrine differentiation in sporadic colorectal cancer has been recognized since decades. In contrast to the clinico-pathologically well-defined pure neuroendocrine tumors and mixed adenoneuroendocrine carcinomas of the colon and rectum, the clinical impact of focal neuroendocrine differentiation in colorectal carcinomas is still controversially discussed. Further insights into the regulation of neuroendocrine differentiation by mTOR pathway components and recent knowledge about a link of enteroendocrine cells to the intestinal stem cell compartment hint at a role of neuroendocrine cells as prognostic marker and putative therapeutic target in sporadic colorectal cancer.