Expression of Neuroendocrine Markers in Undifferentiated Carcinomas of the Gastrointestinal Tract

http://www.jco.org/cgi/content/full/23/21/4795

Journal of Clinical Oncology, Vol 23, No 21 (July 20), 2005: pp. 4795
© 2005 American Society of Clinical Oncology
DOI: 10.1200/JCO.2005.05.218

Expression of Neuroendocrine Markers in Undifferentiated Carcinomas of the
Gastrointestinal Tract

Patricia Grabowski, Hans Scherübl

Medizinische Klinik I, Charité?Campus Benjamin Franklin, Berlin, Germany

To the Editor:

In the July 1, 2004, issue of the Journal of Clinical Oncology, Brenner et
al1 have provided an excellent review on small-cell undifferentiated
carcinomas of the gastrointestinal tract. However, we want to point out
that immunohistochemical staining for neuroendocrine markers is often
positive in undifferentiated gastrointestinal cancers. In a recent series
of 20 undifferentiated colorectal cancers, representing 0.8% of 2,530
colorectal cancers treated at a single institution, nine (45%) of the 20
undifferentiated cancers were found to express neuroendocrine markers.2
Interestingly, neuroendocrine marker?positive undifferentiated cancers
differed from neuroendocrine marker?negative undifferentiated cancers in
the expression of epidermal growth factor receptor (EGFR). Although none
of the nine neuroendocrine marker?positive cancers stained positive for
EGFR expression, the 11 neuroendocrine marker?negative cancers expressed
EGFR immunohistochemically (see Fig 1). Moreover, neuroendocrine
differentiation was of prognostic relevance. Neuroendocrine
marker?negative undifferentiated colorectal cancers were diagnosed at an
earlier stage and had a more favorable overall survival than
neuroendocrine marker?positive undifferentiated colorectal carcinomas (45%
v 11% survivors after 2 years; P < .001). The latter manifested at an
earlier age (51.9 years v 63.6 years), a finding that may well reflect
their aggressive tumor biology. Noteworthy is the fact that partial
neuroendocrine differentiation also predicts a less favorable clinical
course in Dukes' C colorectal adenocarcinoma.3



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Fig 1. Immunohistochemical detection of epidermal growth factor
receptor (EGFR) -expression in undifferentiated colorectal cancers. (A)
Lack of EGFR-staining in an undifferentiated colorectal carcinoma with
neuroendocrine features (representative slide of a total of nine cancers);
(B) positive immunohistochemical staining for EGFR (in red color) in an
undifferentiated colorectal carcinoma without neuroendocrine features
(representative slide of a total of eleven cancers) The cutoff for
immunohistochemical EGFR-positivity was set at 10% or more EGFR-positive
tumor cells. Bar = 100 µm.


Undifferentiated neuroendocrine carcinomas are not thought to derive from
benign orthotopic neuroendocrine epithelial cells4; instead, the most
favored concept currently is that they are of stem cell origin. This means
that a single epithelial cell, even if malignant, can give rise to all
cell types seen in the colorectal epithelium.5 This concept also explains
the occurrence of bi- or multiphenotypic tumors. In line with this notion,
Vortmeyer et al6 observed identical genetic alterations in synchronous
poorly differentiated colorectal neuroendocrine carcinomas and associated
adenocarcinomas.

We suggest that the expression of neuroendocrine markers should be
evaluated in undifferentiated carcinomas of the gastrointestinal tract,
because neuroendocrine differentiation is of prognostic value and will
probably have therapeutic implications in the near future.

Authors' Disclosures of Potential Conflicts of Interest

The following authors and their immediate family members have indicated a
financial interest. No conflict exists for drugs or devices used in a
study if they are not being evaluated as part of the investigation.
Consultant/Advisory Role: Hans Scherubl, AstraZeneca. For a detailed
description of this category, or for more information about ASCO's
conflict of interest policy, please refer to the Author Disclosure
Declaration and Disclosures of Potential Conflicts of Interest found in
Information for Contributors in the front of each issue.

REFERENCES

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alterations in poorly differentiated colorectal neuroendocrine carcinomas
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1997[Abstract/Free Full Text]

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