Adenomatous Polyposis Coli, Mismatch Repair, and Microsatellite Instability in Colorectal Cancer Based on Different Locations
Abstract: 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. Conclusion: 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.
Author: Rustam Effendi-YS dkk
Journal Code: jpkedokterangg130271