Colorectal carcinoma from Saudi Arabia. Analysis of MLH-1, MSH-2 and p53 genes by immunohistochemistry and tissue microarray analysis.
OBJECTIVE
To document the incidence and role of p53 and DNA mismatch repair proteins in colorectal carcinomas, and to evaluate the relative frequency of major molecular pathways in colorectal cancers from Saudi Arabia.


METHODS
We collected the formalin fixed, paraffin embedded tissues from 154 colorectal tumors (83 patients from King Faisal Specialist Hospital and Research Centre and 71 from Saudi Aramco Dhahran Health Centre) between January 1989 and December 2003. We analyzed the p53 and mismatch repair gene expression (hMSH-2, hMLH-1) by immunohistochemistry in tissue microarray format.


RESULTS
Expression loss of at least one mismatch repair gene was found in 33.8% of cases and significantly associated with the right-sided tumor location (p=0.0047). The p53 positivity was observed in 57.5% of tumors, and was inversely linked to expression loss of mismatch repair genes (p=0.0102).


CONCLUSIONS
The strong confirmation of the previously established associations between tumor phenotype, and mismatch repair gene alteration provided strong evidence for the validity of our experimental approach. Together with the higher incidence of right sided location in Saudi (46.6%) than in Western colon cancers (34.9%), the observed high prevalence of mismatch gene expression loss in Saudi tumors argues for a higher importance of microsatellite instability in this population. If confirmed, it will be interesting to see whether an increased level of familial or sporadic microsatellite instability cases is causing this variation.
Al-Kuraya
Khawla S
KS
Research Research Centre, King Faisal Specialist Hospital, Riyadh, Kingdom of Saudi Arabia. kkuraya@kfshrc.edu.sa
Bavi
Prashant P
PP
Ezzat
Adnan A
AA
Al-Dayel
Fouad A
FA
Uddin
Shahab
S
Atizado
Valerie L
VL
Al-Jomah
Naif A
NA
Amr
Samir S
SS
Sheikh
Salwa S
SS
Sauter
Guido
G
Simon
Ronald
R
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012529:Saudi Arabia / Q000453:epidemiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein