Location-related differences in sporadic microsatellite unstable colorectal cancer.
BACKGROUND
Microsatellite unstable CRC is associated with female gender, large tumours, and poor differentiation. However, there are few reports about the characteristics and differences of sporadic microsatellite unstable CRC based on tumour location.


OBJECTIVE
Site-specific heterogeneity of sporadic microsatellite unstable colorectal cancer (CRC) based on location was elucidated.


METHODS
We enrolled 164 CRC patients with high-frequency microsatellite instability (MSI-H) from the prospective database of 2686 consecutive CRC patients who underwent surgical resection. We analysed microsatellite instability (MSI) and expression of mismatch repair (MMR) proteins (MLH1, MSH2, and MSH6).


RESULTS
Among the 164 MSI-H CRC, 105 (64.0%) were located in the proximal colon and 59 (36.0%) were located in the distal colon. The proximal MSI-H CRC was predominantly in female (p=0.014), had a more aggressive differentiation (p=0.001), was of advanced stage (p=0.035), and had a frequent loss of MLH1 expression (p=0.005) compared to the distal MSI-H CRC.


CONCLUSIONS
There were different clinicopathologic characteristics and MMR protein expression between proximal and distal MSI-H CRC. These findings suggest that the underlying carcinogenic pathway or molecular background differs according to location, despite being microsatellite unstable CRC.
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Yong Kwon
YK
Cho
Hee Cheol
HC
Kim
Seok-Hyung
SH
Kim
Jun Ho
JH
Park
Hae-Ran
HR
Yun
Yong Beom
YB
Cho
Seong Hyeon
SH
Yun
Woo Yong
WY
Lee
Ho-Kyung
HK
Chun
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017678:Sex Distribution
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein