Journal of Pathology
J Pathol 2000; 192: 560±563.
Letters to the Editor
Re. article entitled `Keratin 20 is a speci®c marker of
submicroscopic lymph node metastases in colorectal
cancer: validation by K-RAS mutations
I read with interest the article by Yun and colleagues
[1] describing keratin 20 as a speci®c marker for nodal
metastases in patients with colorectal cancer. They
rightly emphasize the very restricted tissue expression
pro®le of keratin 20 but do not refer to the seminal
work by Moll and his group, who cloned the gene for
this most recently identi®ed keratin [2] and investigated
a wide range of tissues to determine expression
patterns and speci®city. They established that, as well
as gastrointestinal epithelium, keratin 20 is expressed
in urothelium and in Merkel cells. In normal urothe-
lium, the expression is differentiation-associated, being
restricted to super®cial `umbrella' cells and to occa-
sional intermediate cells [2±4]. However, as in the
gastrointestinal tract, expression becomes dysregulated
in neoplastic transformation, extending through the
full thickness of dysplastic urothelium and present in
invasive foci [2±6]. The panel of tissues (other than
bowel) investigated by Yun et al. by RT-PCR [1]
consisted largely of non-epithelial tissues, which do not
generally express keratins, and speci®cally, it did not
include bladder. Although their results concerning the
value of cytokeratin 20 detection in the staging of
patients with colorectal cancer may be promising,
they cannot be based on the absolute speci®city of
keratin 20 for gastrointestinal epithelium since meta-
Letter to the Editor
Authors' reply
We welcome the points by Dr Harnden regarding our
article on validation of K20 as a tissue-speci®c marker
of colorectal cancer by K-RAS mutation analysis [1].
We are aware of the seminal work by Moll et al. [2,3]
and have referenced them in our earlier papers
regarding the detection of submicroscopic disease in
colorectal and breast cancer [4±6]. Dr Harnden
correctly points out that cytokeratin 20 (K20) is also
expressed in urothelium and Merkel cells, and is useful
for the diagnosis of urothelial papillomas [7,8]. We
accept his point that the speci®city of K20 RT-PCR as
a tissue-speci®c marker of submicroscopic lymph node
metastases in patients with colorectal cancer can
potentially be confounded by urothelial carcinoma,
Copyright # 2000 John Wiley & Sons, Ltd.
static urothelial carcinoma may be a confounding
factor.
P. Harnden
Department of Histopathology, St. James's University Hospital,
Beckett Street, Leeds LS9 7TF, UK
References
1. Yun K, Merrie AEH, Gunn J, Phillips LV, McCall JL. Keratin 20
is a speci®c marker of submicroscopic lymph node metastases in
colorectal cancer: validation by K-RAS mutations. J Pathol 2000;
191: 21±26.
2. Moll R, Zimbelmann R, Goldschmidt MD, et al. The human gene
encoding cytokeratin 20 and its expression during fetal develop-
ment and in gastrointestinal carcinomas. Differentiation 1993; 53:
75±93.
3. Moll R. Molecular diversity of cytokeratins: signi®cance for cell
and tumor differentiation. Acta Histochem, Suppl 1991; 41:
117±127.
4. Moll R, Lowe A, Laufer J, Franke WW. Cytokeratin 20 in human
carcinomas. A new histodiagnostic marker detected by mono-
clonal antibodies. Am J Pathol 1992; 140: 427±447.
5. Harnden P, Eardley I, Joyce AD, Southgate J. Cytokeratin 20 as
an objective marker of urothelial dysplasia. Br J Urol 1996; 78:
870±875.
6. Harnden P, Mahmood N, Southgate J. Expression of cytokeratin
20 rede®nes urothelial papillomas of the bladder. Lancet 1999;
353: 974±977.
although it would be highly unusual for urothelial
carcinoma to metastasize to the colonic mesenteric
lymph nodes.
RT-PCR offers potential advantages in the detection
of occult metastases over immunohistochemistry. It is
up to 100-fold more sensitive in the detection of
malignant cells [9]. It is at this extreme sensitivity that
very low level or illegitimate gene expression can be
detected, making speci®city an important issue. The
importance of the tissue panel in our manuscript,
where six out of ten tissues used contain epithelial
tissue components, is that K20 gene expression is
restricted only to bowel and its cancer by analysis with
a highly sensitive RT-PCR technique.