Scheda a cura di:
Claudio Doglioni (GYM), Mattia
Barbareschi (GYM), Francesca Guddo (Pa)
CDX-2
Bibliografia
essenziale
Cdx-2 homeobox gene expression is
a reliable marker of colorectal adenocarcinoma metastases to the lungs.
M.
Barbareschi , B. Murer, T.V. Colby , M. Chilosi , E. Macri, M. Loda, C. Doglioni
Am J Surg Pathol
2003, 2003 Feb;27(2):141-9.
Background.
Lung metastases from colorectal
carcinomas (CRC) can be resected with improved survival. The distinction between
primary lung adenocarcinomas and metastases from CRC may sometimes be difficult,
especially on cytological specimens or
small bronchoscopic biopsies. Immunohistochemistry may be of help in this
setting: available markers include TTF-1 and SP-A
which are markers of lung origin, while there are no good markers of
intestinal origin, beside cytokeratin 7 and 20 coexpression pattern, which is
not very specific. The nuclear CDX-2 transcription factor, which is
the product of a homeobox
gene necessary for intestinal organogenesis,
is expressed in normal colonic epithelia and most colorectal
adenocarcinomas, and could potentially be of diagnostic usefulness.
Aim.
Our aim was to
investigate CDX-2 immunohistochemical expression using a new monoclonal
antibody, and to verify if CDX-2 can
be a reliable marker to identify the colorectal origin of lung metastases.
Material and Methods.
CDX-2 expression was evaluated in formalin fixed paraffin embedded samples of
normal adult human tissues (50 samples) and in
299 surgically resected carcinomas of different origins, including 125
non lung adenocarcinomas, 117 primary lung tumors, 5 mesotheliomas and 52
adenocarcinomas metastatic to the lung. CDX-2 was also evaluated on a series of
20 bioptic and 10 cytological specimens (5 cases of colorectal metastases
to the lung, 5 cases of metastases from other organs and 10 primary lung
adenocarcinomas).
Results.
In normal tissues, CDX-2 immunoreactivity was observed only in ileal and
colorectal epithelia. CDX-2 was expressed in
almost all primary and metastatic CRC (88 out of 90) and was never observed in
primary lung tumors. CDX-2 was also expressed in a limited group of
adenocarcinomas of other sites (gastric, bilio-pancreatic and mucinous ovarian
adenocarcinomas). CDX-2 could be easily detected in all bioptic and
cytological samples of CRC metastases.
Conclusions.
CDX-2 is a reliable, specific and sensitive immunohistochemical marker of normal
and neoplastic intestinal epithelium. CDX-2 can be easily applied to routine
histological and cytological material and is
therefore a useful marker in the
differential diagnosis of primary versus metastatic adenocarcinomas in the lung,
and among metastases from an unknown primary, supports intestinal origin.
Am
J Surg Pathol. 2003 Mar;27(3):303-10.
CDX2,
a highly sensitive and specific marker of adenocarcinomas of intestinal origin:
an immunohistochemical survey of 476 primary and metastatic carcinomas.
Werling
RW, Yaziji H, Bacchi CE, Gown AM.
PhenoPath
Laboratories and IRIS, 551 N. 34th Street, Seattle, WA 98103, USA.
CDX2 is a recently cloned homeobox gene that encodes an intestine-specific
transcription factor, expressed in the nuclei of epithelial cells throughout the
intestine, from duodenum to rectum. While expression of CDX2 protein in primary
and metastatic colorectal carcinomas has been previously documented, neither the
sensitivity nor the specificity of CDX2 expression, as determined by
immunohistochemistry, for colorectal adenocarcinoma has been determined. We
performed an immunohistochemical survey of 476 tumors with a monoclonal
antibody, CDX2-88, including 89 tumors from the colon and duodenum and 95 tumors
from other gastrointestinal sites, including the esophagus, stomach,
pancreatobiliary system, gastrointestinal carcinoids, and liver. CDX2 was
expressed uniformly (that is, in 76-100% of tumor cells) in all but one of the
evaluated colorectal and duodenal tumors. High-level expression of CDX2 was also
found, however, in mucinous ovarian carcinomas and adenocarcinomas primary to
the urinary bladder of which 64% and 100% were positive, respectively. Gastric,
gastroesophageal, and pancreatic adenocarcinomas and cholangiocarcinomas all
showed similar, heterogeneous patterns of CDX2 expression. Most tumors in each
group showed CDX2 expression by a minority of cells, whereas a substantial
minority of cases in each group was completely negative and a smaller minority
was uniformly positive. Gastrointestinal carcinoids gave similarly varied
results, but the majority (58%) was negative. Hepatocellular carcinomas showed
no expression of CDX2. Only very rare examples of carcinomas of the
genitourinary and gynecologic tracts, breast, lung, and head and neck showed
significant levels of CDX2 expression. In this study of primary and metastatic
epithelial tumors, uniform CDX2 expression is demonstrated to be an exquisitely
sensitive and highly, but incompletely, specific marker of intestinal
adenocarcinomas. Compared with villin, a previously described marker of GI
adenocarcinomas, CDX2 demonstrated superior sensitivity and comparable
specificity. CDX2 expression can be seen, however, in selected non-GI
adenocarcinomas such as mucinous ovarian carcinomas and adenocarcinomas of the
urinary bladder.
J
Cell Sci. 2003 Apr 15;116(Pt 8):1429-36.
Espressione
di cdx2 nella metaplasia intestinale
J
Gastroenterol. 2003;38(1):14-22.
Aberrant
expression of CDX2 in Barrett's epithelium and inflammatory esophageal
mucosa.
Eda
A, Osawa H, Satoh K, Yanaka I, Kihira K, Ishino Y, Mutoh H, Sugano K.
Department
of Internal Medicine, Jichi Medical School, Yakushiji, Kawachi, Tochigi
329-0438, Japan.
BACKGROUND: There have been no detailed reports directly comparing the
expression of CDX1 with that of CDX2 in the inflammatory esophageal mucosa and
Barrett's epithelium. The present study was designed to examine the expression
of CDX 1/2 in inflammatory esophageal mucosa with or without Barrett's
epithelium. METHODS: The expression of CDX1/2 genes was analyzed using the
reverse transcriptase-polymerase chain reaction (RT-PCR) in 34 human esophageal
biopsy specimens, and CDX2 expression was also evaluated immunohistochemically,
using anti-human CDX2 monoclonal antibody. The biopsy specimens for RNA
extraction were taken endoscopically from esophageal mucosa with mucosal break
due to gastroesophageal reflux disease (GERD), Barrett's epithelium, and normal
epithelium. The expressions of mucin markers (MUC2) and intestine-specific genes
(sucrase-isomal-tase, human defensin-5, alkaline phosphatase) were also
comparatively analyzed. RESULTS: CDX1/2 expression was not found in the normal
esophageal mucosa. The prevalence of CDX1/2 mRNA expression was significantly
higher in the mucosa with Barrett's epithelium than in the mucosa without
Barrett's epithelium. It is noteworthy, however, that the CDX2 mRNA expression
was initiated at the stage of esophagitis, when neither CDX1 nor
intestine-specific genes had emerged yet. In contrast to CDX2, CDX1 was
expressed only in Barrett's epithelium. Immunohistochemical study demonstrated
strong and extensive nuclear immunoreactivity for CDX2 in Barrett's epithelium.
Furthermore, fine granular cytoplasmic staining was also observed in the
cytoplasm in Barrett's epithelium, as well as in inflammatory esophageal mucosa.
CONCLUSIONS: We report here, for the first time, that CDX2 is expressed in
patients with Barrett's epithelium and inflammatory esophageal mucosa. These
findings imply that the expression of CDX2 may be an early event leading to the
development of Barrett's esophagus.
Chronic
acid exposure leads to activation of the cdx2 intestinal homeobox gene in a
long-term culture of mouse esophageal keratinocytes.
Marchetti
M, Caliot E, Pringault E. Laboratory of Lympho-Epithelial Interactions,
Department of Cell Biology and Infection, Pasteur Institute, 28, Rue du Dr Roux,
75015 Paris, France.
To explore mechanisms whereby Malpighian keratinocytes can transdifferentiate
into an intestinal-like epithelium, as observed in the early steps of Barrett's
esophagus (BE) development, long-standing cultures of esophageal keratinocytes
derived from normal mouse esophageal explants were developed. These cells were
able to form multilayers and to differentiate on filter support by the formation
of differentiated layers of basal cells (cytokeratine 14 positive) on which
secondary suprabasal cell layers (cytokeratine 4 positive) spontaneously
developed. Thus, these cultured cells, referred to as P3E6, reproduced, at least
in part, the proliferation and stratification pattern existing in the normal
esophagus. Because chronic exposure to acid pH is known to be a critical factor
for BE development, culture medium at pH 3.5 was added into the apical chamber
of cell cultures. This led to a decrease in the overall number of cells but it
did not affect cell proliferation. Furthermore, external acid environment
triggered expression of the GFP reporter gene fused downstream of the cdx2
intestinal homeogene regulatory sequences in P3E6 transfected cells. Expression
of the endogenous CDX2 protein, detected by western blot and immunocytochemical
analysis, correlated with promoter activation. These findings demonstrate that
chronic exposure of esophageal keratinocytes to acid pH induces transcription of
cdx2, an intestinal specific homeobox gene known to play a critical role in the
differentiation and maintenance of intestinal epithelial functions. The results
suggest that chronic acid exposure can modify the fate of P3E6 esophageal
keratinocytes towards an intestinal program. This can be a key step in the
development of intestinal metaplasia often observed in esophagus-cardia junction.
Deregulated
homeobox gene expression in cancer: cause or consequence?
Abate-Shen C.
Nat Rev Cancer 2002 Oct;2(10):777-85
Homeobox genes comprise a large and essential family of developmental regulators
that are vital for all aspects of growth and differentiation. Although many
studies have reported their deregulated expression in cancer, few studies have
established direct functional roles for homeobox genes in carcinogenesis.
Nonetheless, most cases of deregulated homeobox gene expression in cancer
conform to a simple rule: those that are normally expressed in undifferentiated
cells are upregulated in cancer, whereas those that are normally expressed in
differentiated tissues are downregulated in cancer.
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Ectopic
expression of homeodomain protein CDX2 in intestinal metaplasia and carcinomas
of the stomach.
Bai
YQ, Yamamoto H, Akiyama Y, Tanaka H,
Takizawa T, Koike M, Kenji Yagi O, Saitoh K, Takeshita K, Iwai T, Yuasa Y.
Cancer Lett 2002 Feb 8;176(1):47-55
The roles of CDX2 and CDX1 homeobox genes during gastric carcinogenesis remain
poorly defined. We have studied the expression of CDX2/1 in gastric cancers and
intestinal metaplasia (IM) of 69 gastric carcinoma patients by
immunohistochemistry. CDX2/1 were shown to be ectopically overexpressed in IM in
41 (85%) of 48, and 47 (90%) of 52 cases, respectively. The expression of CDX2/1
was detected in 38 (55%) and 51 (74%) of the 69 gastric carcinomas, respectively.
The histological type of the gastric carcinomas was independently associated
with CDX2 expression, but not with that of CDX1, with higher CDX2 expression in
intestinal type (differentiated type) than in diffuse type (undifferentiated
type) gastric carcinomas. Our results thus suggest that CDX2 and CDX1 may play a
role during IM formation and gastric carcinogenesis.
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Reprogramming
of intestinal differentiation and intercalary regeneration in Cdx2 mutant mice.
Beck
F, Chawengsaksophak K, Waring P, Playford RJ, Furness JB.
Proc Natl Acad Sci U S
A 1999 Jun 22;96(13):7318-23
Howard
Florey Institute of Experimental Physiology and Medicine, University of
Melbourne, Melbourne 3052, Australia. fb22@le.ac.uk
The homeobox gene Cdx2, a homologue of the Drosophila gene caudal, has been
implicated in the control of cell differentiation in the intestinal epithelium.
Recently, we showed that mice in which one allele of the Cdx2 gene had been
inactivated by homologous recombination developed multiple intestinal polyp-like
lesions that did not express Cdx2 and that contained areas of squamous
metaplasia in the form of keratinizing stratified squamous epithelium, similar
to that occurring in the mouse esophagus and forestomach. We have now examined
colonic lesions from 98 Cdx2+/- mice and report that the lesions are composed of
heterotopic stomach and small intestinal mucosa. We conclude that Cdx2 directs
endodermal differentiation toward a caudal phenotype and that haploinsufficient
levels of expression in the developing distal intestine lead to homeotic
transformation to a more rostral endodermal phenotype, such as forestomach
epithelium that does not express Cdx2 during normal development. Intercalary
growth (epimorphic regeneration), which previously has never been described in
mammals, then occurs, resulting in the ordered "filling in" of tissue
types at the discontinuity between the gastric and colonic epithelia. This
intercalary growth in a restricted space results in the formation of the
polypoid lesions observed.
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Homeosis
and intestinal tumours in Cdx2 mutant mice.
Chawengsaksophak
K, James R, Hammond VE, Kontgen F, Beck F.
Nature 1997 Mar 6;386(6620):84-7
Howard Florey Institute of Experimental Physiology and Medicine, University of
Melbourne, Parkville, Victoria, Australia.
In Drosophila, disturbing the expression of the homeobox gene caudal causes a
severe disruption in body segmentation and global body patterning. There are
three mouse homologues of Drosophila caudal: Cdx1 (ref. 2), Cdx2 (ref. 3) and
Cdx4 (ref. 4). We have generated a null mutation of murine Cdx2 by homologous
recombination. Cdx2 homozygote null mutants die between 3.5 and 5.5 days post
coitum (d.p.c.). Cdx2 heterozygote mutants exhibit a variable phenotype, with
many showing tail abnormalities or stunted growth. Skeletal analysis
demonstrates a homeotic shift of vertebrae and compatible malformations of the
ribs. Within the first three months of life, 90% of Cdx2 heterozygotes develop
multiple intestinal adenomatous polyps, particularly in the proximal colon.
These polyps occasionally contain areas of true metaplasia. In contrast to the
surrounding intestinal epithelium, the neoplastic cells do not express Cdx2 from
the remaining allele. These results suggest that Cdx2 mutation is the primary
event in the genesis of some intestinal tumours.
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Cloning
and chromosome assignment of the human CDX2 gene.
Drummond
F, Putt W, Fox M, Edwards YH.
Ann Hum Genet 1997 Sep;61 ( Pt 5):393-400
MRC Human Biochemical Genetics Unit, University College London.
The caudal-type homeobox gene Cdx2 encodes a transcription factor which is
expressed in the intestine and is thought to play an important role in the
proliferation and differentiation of intestinal epithelial cells. Mice
heterozygous for null mutations in the caudal-type homeobox gene Cdx2 show
multiple adenomatous polyps in the proximal colon in addition to skeletal
problems associated with abnormal segmentation. In human colorectal cancer the
expression of both CDX2 and carbonic anhydrase 1, a gene regulated by CDX2, is
reduced or absent. It is possible that mutation of CDX2 is a primary event in
the origin of some colorectal cancers. We have cloned human CDX2 cDNA and report
here the nucleotide and protein sequences and assignment of the human gene to
chromosome 13q12-13.
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Cdx-2
homeodomain protein expression in human and rat colorectal adenoma and
carcinoma.
Ee
HC, Erler T, Bhathal PS, Young GP, James RJ.
Am J Pathol 1995 Sep;147(3):586-92
University of Melbourne Department of Medicine, Victoria, Australia.
Cancers share many similarities in growth patterns, cellular morphology, and
oncofetal antigen expression with embryonic tissue. To better understand the
mechanisms underlying malignant transformation and its relationship to
developmental processes, we studied the expression of Cdx-2, an intestinal
epithelium-specific homeodomain protein, in colorectal adenoma and carcinoma. By
immunohistochemistry with a polyclonal Cdx-2 antibody we have shown that Cdx-2
expression is markedly reduced in the later stages of human colorectal
carcinogenesis, namely, high grade dysplasia and invasive carcinoma. The same
findings occur in 1,2-dimethylhydrazine-induced rat colorectal tumors,
confirming the parallels between the rat model and the human disease. As
homeodomain proteins play major roles in directing the regionalization of body
parts and in organogenesis and cellular phenotypic specification, a reduction of
Cdx-2 expression in the late stages of colorectal carcinogenesis may reflect a
concomitant deviation of the neoplastic tissue from the normal intestinal
epithelial phenotype.
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Expression
of CDX2 in normal and neoplastic human colon tissue and during differentiation
of an in vitro model system.
Qualtrough
D, Hinoi T, Fearon E, Paraskeva C.
Gut 2002 Aug;51(2):184-90
Cancer Research UK, Colorectal Tumour Biology Research Group, Department of
Pathology and Microbiology, School of Medical Sciences, University of Bristol,
University Walk, Bristol BS8 1TD, UK.
BACKGROUND: The Cdx genes are expressed in the colorectal epithelium and are
frequently downregulated during tumorigenesis. Overexpression of Cdx genes has
been shown previously to result in cellular differentiation. AIM: To study
expression of CDX2 in normal and neoplastic human colon using a newly isolated
monoclonal antibody. To define expression of CDX1 and CDX2 in an in vitro model
system of colorectal tumour progression and to ascertain whether these are
subject to regulation during differentiation. METHODS: Normal and neoplastic
human colon was immunostained for CDX2. CDX1 and CDX2 expression was assayed in
cell lines derived from premalignant colonic adenomas by western blotting.
Differentiation was induced by sodium butyrate treatment or post confluent
growth, and changes in CDX expression compared with carcinoma cell lines with
low levels of CDX expression. RESULTS: CDX2 protein displayed no gradient of
expression within the colonic crypt. Cell lines derived from adenomas, with high
levels of CDX1 and CDX2, showed no regulation of these proteins when induced to
differentiate by butyrate or confluency. CDX expression in these cell lines was
independent of their APC or Ras status. CDX1 and CDX2 were expressed at very low
levels in some carcinoma cell lines and were modestly upregulated on
differentiation but were not restored to levels seen in adenoma cells.
CONCLUSION: The lack of significant regulation on cellular differentiation and
the absence of a detectable gradient in the crypt implies that CDX2 may confer
tissue specificity but may not play the previously suggested role in crypt
patterning.
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CDX2
regulates liver intestine-cadherin expression in normal and malignant colon
epithelium and intestinal metaplasia.
Hinoi
T, Lucas PC, Kuick R, Hanash S, Cho KR, Fearon ER.
Gastroenterology 2002 Nov;123(5):1565-77
Department of Internal Medicine, University of Michigan Medical School,
Ann Arbor, Michigan, USA.
BACKGROUND & AIMS: The intestine-specific caudal-related homeobox
transcription factor CDX2 seems to play a key role in intestinal development and
differentiation. Inactivation of one Cdx2 allele predisposes mice to develop
colon polyps, and loss of CDX2 expression is a feature of some poorly
differentiated colon carcinomas in humans. Conversely, aberrant CDX2 expression
is often seen in intestinal metaplasias in the stomach and esophagus and in some
gastric carcinomas. To better understand CDX2 function, we sought to define
CDX2-regulated genes. METHODS: HT-29 colon cancer cells with minimal endogenous
CDX2 expression were engineered to express exogenous CDX2, and gene expression
changes relative to control cells were assessed using high-density
oligonucleotide arrays. RESULTS: The gene for liver intestine (LI)-cadherin (cadherin
17) was strongly induced by CDX2 in HT-29. In other colorectal cancer lines,
endogenous CDX2 and LI-cadherin expression were well correlated. Activation of a
ligand-regulated form of CDX2 rapidly induced LI-cadherin gene expression, even
in the presence of protein synthesis inhibitor. Analysis of the 5'-flanking
region of the LI-cadherin gene defined 2 CDX2 responsive elements, and chromatin
immunoprecipitation assays indicate CDX2 binds to the elements. In primary
colorectal cancers and intestinal metaplasias in the stomach, CDX2 and
LI-cadherin expression were tightly correlated. CONCLUSIONS: CDX2 regulates
LI-cadherin gene expression in normal, metaplastic, and neoplastic tissues of
the gastrointestinal tract via binding to elements in the 5'-flanking region of
the gene. Given the well-established roles of cadherins in morphogenesis and
differentiation, LI-cadherin may be a key factor mediating CDX2 function in
intestinal cell fate determination.
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Loss of CDX2 expression and microsatellite instability
are prominent features of large cell minimally differentiated carcinomas of the
colon.
Hinoi
T, Tani M, Lucas PC, Caca K, Dunn RL, Macri E, Loda M, Appelman HD, Cho KR,
Fearon ER.
Am J Pathol 2001 Dec;159(6):2239-48
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
48109, USA.
Most large bowel cancers are moderately to well-differentiated adenocarcinomas
comprised chiefly or entirely of glands lined by tall columnar cells. We have
identified a subset of poorly differentiated colon carcinomas with a distinctive
histopathological appearance that we term large cell minimally differentiated
carcinomas (LCMDCs). These tumors likely include a group of poorly
differentiated carcinomas previously described by others as medullary
adenocarcinomas. To better understand the pathogenesis of these uncommon
neoplasms, we compared molecular features of 15 LCMDCs to those present in 25
differentiated adenocarcinomas (DACs) of the colon. Tumors were examined for
alterations commonly seen in typical colorectal carcinomas, including increased
p53 and beta-catenin immunoreactivity, K-ras gene mutations, microsatellite
instability, and loss of heterozygosity of markers on chromosomes 5q, 17p, and
18q. In addition, tumors were evaluated by immunohistochemistry for CDX2, a
homeobox protein whose expression in normal adult tissues is restricted to
intestinal and colonic epithelium. Markedly reduced or absent CDX2 expression
was noted in 13 of 15 (87%) LCMDCs, whereas only 1 of the 25 (4%) DACs showed
reduced CDX2 expression (P < 0.001). Nine of 15 (60%) LCMDCs had the
high-frequency microsatellite instability phenotype, but only 2 of 25 (8%) DACs
had the high-frequency microsatellite instability phenotype (P = 0.002). Our
findings provide support for the hypothesis that the molecular pathogenesis of
LCMDCs is distinct from that of most DACs. CDX2 alterations and DNA mismatch
repair defects have particularly prominent roles in the development of LCMDCs.
Cdx2 ectopic expression
induces gastric intestinal metaplasia in transgenic mice.
Silberg
DG, Sullivan J, Kang E, Swain GP, Moffett J, Sund NJ, Sackett SD, Kaestner KH.
Gastroenterology 2002 Mar;122(3):689-96
Department
of Medicine, University of Pennsylvania School of Medicine, Philadelphia,
Pennsylvania 19104, USA. silberg@mail.med.upenn.edu
BACKGROUND & AIMS: Intestinal-type gastric cancer is often preceded by
intestinal metaplasia in humans. The genetic events responsible for the
transdifferentiation that occurs in intestinal metaplasia are not well
understood. Cdx2, a transcription factor whose expression is normally limited to
the intestine, has been detected in gastric intestinal metaplasia. Cdx2 induces
differentiation of intestinal epithelial cells in vitro; therefore, we sought to
establish whether a causal relationship exists between Cdx2 activation and
intestinal metaplasia. METHODS: Cdx2 expression was directed to the gastric
mucosa in transgenic mice using cis-regulatory elements of Foxa3 (Hnf3gamma).
Transgenic mice were analyzed for histologic and gene expression changes.
RESULTS: Histologic examination of the gastric mucosa of the Foxa3/Cdx2 mice
revealed the presence of alcian blue-positive intestinal-type goblet cells, a
hallmark of intestinal metaplasia. In addition, Cdx2 induced the expression of
intestine-specific genes. CONCLUSIONS: Gastric expression of Cdx2 alone was
sufficient to induce intestinal metaplasia in mice. These mice represent a
powerful tool to investigate the molecular mechanisms that promote intestinal
metaplasia. Moreover, as gastric cancer in humans is often preceded by
intestinal metaplasia, the phenotype described here strongly suggests
involvement of Cdx2 in the initiation of the process leading to intestinal
neoplasia of the gastric mucosa.
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CDX2,
a human homologue of Drosophila caudal, is mutated in both alleles in a
replication error positive colorectal cancer.
Wicking
C, Simms LA, Evans T, Walsh M, Chawengsaksophak K, Beck F, Chenevix-Trench G,
Young J, Jass J, Leggett B, Wainwright B.
Oncogene 1998 Aug 6;17(5):657-9
Centre for Molecular and Cellular Biology, University of Queensland, St Lucia,
Australia.
The Cdx2 gene is one of three murine homologues of the Drosophila homeobox gene
caudal. Mice heterozygous for a null mutation in Cdx2 exhibit a variable
phenotype including tail abnormalities, stunted growth and a homeotic shift of
vertebrae. Most strikingly, however, 90% of heterozygous mice were reported to
develop multiple intestinal adenomatous polyps, most notably in the proximal
colon (Chawengsaksophak et al., 1997). These observations led us to propose that
mutation of CDX2 may be involved in the genesis of some human colorectal tumours.
A survey of DNA from 85 colorectal tumours revealed that one with extensive
microsatellite instability (RER+ phenotype) has mutations in both alleles of
CDX2. Both mutations occur in coding regions which contain repetitive elements
and are consistent with those found in RER + tumours.
Gennaio 2003
