Expression of the proto-oncogene c-KIT in normal and tumor tissues from colorectal carcinoma patients.
OBJECTIVE
The proto-oncogene c-KIT encodes a tyrosine kinase receptor essential during embryonic development and postnatal life. Although deregulated expression of c-KIT has been reported, its role in colorectal carcinoma remains controversial: some authors have described a correlation between c-KIT expression and colorectal cancer (CRC), while others have failed to detect the receptor in the majority of neoplasia examined. To address this question, we designed a prospective study to analyze the expression of c-KIT in normal and neoplastic colonic mucosa of the same patient.


METHODS
We analyzed the tissues of 20 patients undergoing surgical resection for colorectal carcinoma by reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry, whose results were correlated with histopathological parameters.


RESULTS
Most patients (90%) showed c-KIT expression in normal tissue both at RNA and protein level, while in neoplastic tissue it was observed in 30% of patients at RNA level and in 10% at protein level. By immunohistochemistry the localization of c-KIT protein in the normal colon was restricted to interstitial cells scattered in the stroma, whereas the non-neoplastic epithelium was always negative. The mucinous carcinomas were all c-KIT negative, whereas the only case in which c-KIT was displayed in the neoplastic epithelium was a G3 adenocarcinoma.


CONCLUSIONS
Most colorectal carcinomas do not express c-KIT. We suggest that c-KIT expression is rarely present in this neoplasia; thus, the use of receptor inhibitors should be conducted in selected sub-groups of colon carcinoma patients, subsequent to the clear demonstration of c-KIT overexpression in the neoplastic cells.
Sammarco
Innocenzo
I
Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Capurso
Gabriele
G
Coppola
Luigi
L
Bonifazi
Antonio Paniccià
AP
Cassetta
Sara
S
Delle Fave
Gianfranco
G
Carrara
Alessandro
A
Grassi
Giovanni Battista
GB
Rossi
Pellegrino
P
Sette
Claudio
C
Geremia
Raffaele
R
D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit