Associations of defect mismatch repair genes with prognosis and heredity in sporadic colorectal cancer.
BACKGROUND
Microsatellite instability arises due to defect mismatch repair (MMR) and occurs in 10-20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives.


METHODS
Tumour tissues from 318 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases.


RESULTS
Forty-seven (15%) tumours displayed MSI. No correlation was seen between patients exhibiting MSI in the tumour and heredity (p = 0.789). Patients with proximal colon cancer and MSI had an improved cancer-specific survival (p = 0.006) and prolonged time to recurrence (p = 0.037). In a multivariate analysis including MSI status, gender, CEA, vascular and neural invasion, patients with MSS and proximal colon cancer had an impaired cancer-specific survival compared with patients with MSI (HR, 4.32; CI, 1.46-12.78). The same prognostic information was also seen in distal colon cancer; no recurrences seen in the eight patients with stages II and III distal colon cancer and MSI, but the difference was not statistically significant.


CONCLUSIONS
No correlation between MSI and heredity for colorectal cancer in first-degree relatives was seen. Patients with MSI tumours had improved survival.
Department of Surgical Science, University of Uppsala, Uppsala, Sweden. Electronic address: arezo_g@hotmail.com.
L
L
Ghanipour
Division of Oncology-Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
K
K
Jirström
Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology, University of Uppsala, Uppsala, Sweden.
M
M
Sundström
Department of Radiology, Oncology and Radiation Science, University of Uppsala, Uppsala, Sweden.
B
B
Glimelius
Department of Surgical Science, University of Uppsala, Uppsala, Sweden.
H
H
Birgisson
D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D000070956:MutL Proteins / Q000235:genetics; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012307:Risk Factors; D015996:Survival Rate
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C117307:KRAS protein, human; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; C088996:PMS1 protein, human; D048493:Proto-Oncogene Proteins B-raf; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein; D016283:Proto-Oncogene Proteins p21(ras)
Colorectal cancer; Heredity; MSI; MSS; Prognosis; TMA