Difference between proximal and distal microsatellite-unstable sporadic colorectal cancers: analysis of clinicopathological and molecular features and prognoses.
BACKGROUND
Distal microsatellite instability (MSI)-high colorectal cancers (CRCs) have been investigated by few studies and are generally regarded as having similar features to proximal MSI-high CRCs. In the present study, we aimed to elucidate whether distal sporadic MSI-high CRCs displayed distinguished clinicopathological and molecular features from proximal MSI-high CRCs.


METHODS
All patients who underwent their first surgical resections for stage I-IV sporadic CRCs between August 2003 and August 2006 were initially considered for enrollment, and their MSI data were prospectively collected. Among them, 135 patients with MSI-high CRCs (86 proximal and 49 distal CRCs) were finally identified. The clinicopathological and molecular characteristics, and prognosis of these cases with MSI-high CRCs were reviewed and compared according to tumor site (proximal versus distal).


RESULTS
Distal MSI-high CRCs showed significantly more frequent association with younger age, male gender, differentiated histology, small tumor size, distant metastasis, stability in BAT25 and BAT26, and hMLH1 expression on immunohistochemical staining as compared with proximal MSI-high CRCs. In addition, distal MSI-high CRCs demonstrated significantly worse 3-year overall and disease-free survival rates than proximal MSI-high CRCs (87.0% versus 97.4%; 81.6% versus 95.9%). For stage III-IV CRCs, distal MSI-high CRCs also showed significantly worse 3-year overall and disease-free survival rates than proximal MSI-high CRCs (72.2% vs. 90.5%; 58.3% vs. 94.4%).


CONCLUSIONS
These results indicated that distal sporadic MSI-high CRCs formed a distinct subgroup with distinguished clinicopathological and molecular features from proximal MSI-high CRCs. In addition, this study demonstrated that distal MSI-high CRCs had worse prognosis than proximal MSI-high CRCs.
Kim
Young-Ho
YH
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Min
Byung-Hoon
BH
Kim
Sue Jin
SJ
Choi
Hyo Kyung
HK
Kim
Kyoung-Mee
KM
Chun
Ho-Kyung
HK
Lee
Hyuk
H
Kim
Jin Yong
JY
Chang
Dong Kyung
DK
Son
Hee Jung
HJ
Rhee
Poong-Lyul
PL
Rhee
Jong Chul
JC
Kim
Jae J
JJ
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
D048868:Adaptor Proteins, Signal Transducing; C516892:BAT26 microsatellite DNA; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005819:Genetic Markers; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1