Adenomatous Polyposis Coli, mismatch repair, and microsatellite instability in colorectal cancer based on different locations.
OBJECTIVE
to examine the protein expression negative (PEN) of Adenomatous Polyposis Coli (APC), Mismatch Repair (MMR), and Microsatellite Instability (MSI) status of colorectal cancer (CRC), and establish a comparison of those molecular characteristics in CRC location among Indonesian patients in Adam Malik Hospital, Pirngadi Hospital, and other hospitals within the network of Faculty of Medicine University of Sumatera Utara Medan Indonesia.


METHODS
this prospective study was conducted from April to December 2012. Fresh tissues were obtained from colorectal tumor patients. The APC-PEN, MMR (MLH1, MSH2, PMS2, MSH6)-PEN, were assessed by immunohistochemistry, and MSI by PCR using 5 microsatellite markers (BAT25, BAT26, D2S123, D5S346, D17S250), as independent variables. The tumour locations as dependent variables were divided into proximal colon (caecum, ascending colon, transverse colon); distal colon (splenic flexure, descending colon, sigmoid) and rectum. The comparative study were done by bivariate and multivariate analysis.


RESULTS
there were 77 cases of colorectal adenocarsinoma. MMR-PEN was found in 54 of 77 (70.1%). MLH1-PEN was different between distal colon and rectal cancer (p=0.008); MSH6-PEN was different between proximal colon and rectal cancer (p= 0.020). Multivariate analysis showed: MLH1-PEN was related to cancer location (p=0.006) with OR 0.12 (95% CI 0.026-0.547). It had 0.12 times probability to be found in distal than rectum. MLH1-PEN had 10 times higher probability to be found in proximal than in distal (p=0.037). MSH6-PEN was related to the location (p=0.026) with OR 0.165 (95% CI 0.034-0.803), and had 0.165 times probability to be found in proximal than rectum; and 11 times higher probability in distal than proximal colon (p=0.043). APC-PEN was related to the location (p=0.020), with OR 6.897 (95% CI 1.359-34.995), and 6.89 times higher probability in distal than in rectum, with other variables controlled. MSI-H was found in 29 of 77 (37.7%) and MSI-L/MSS in 48 (62.3%). The proportion of MSI-H displayed a tendency to occur in proximal rather than in distal colon or rectal cancer.


CONCLUSIONS
the underlying carcinogenic pathway or molecular background differs according to the cancer locations of CRC patients in this region. MLH1-PEN was prominent in proximal colon cancer, MSH6-PEN in distal colon and rectal cancer, and APC-PEN in distal colon respectively.
Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Adam Malik Hospital, Pirngadi Hospital, Medan, Indonesia.
Rustam
R
Effendi-Y S
Lukman H
LH
Zain
Gontar A
GA
Siregar
Harun R
HR
Lubis
Harun A
HA
Damanik
Lidya I
LI
Laksmi
Jessy
J
Chrestella
D000230:Adenocarcinoma / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D011125:Adenomatous Polyposis Coli / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D003106:Colon / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D053843:DNA Mismatch Repair; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D011446:Prospective Studies; D059467:Transcriptome
D009363:Neoplasm Proteins