Low frequency of defective mismatch repair in a population-based series of upper urothelial carcinoma.
BACKGROUND
Upper urothelial cancer (UUC), i.e. transitional cell carcinomas of the renal pelvis and the ureter, occur at an increased frequency in patients with hereditary nonpolyposis colorectal cancer (HNPCC). Defective mismatch repair (MMR) specifically characterizes HNPCC-associated tumors, but also occurs in subsets of some sporadic tumors, e.g. in gastrointestinal cancer and endometrial cancer.


METHODS
We assessed the contribution of defective MMR to the development of UUC in a population-based series from the southern Swedish Cancer Registry, through microsatellite instability (MSI) analysis and immunohistochemical evaluation of expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6.


RESULTS
A MSI-high phenotype was identified in 9/216 (4%) successfully analyzed patients and a MSI-low phenotype in 5/216 (2%). Loss of MMR protein immunostaining was found in 11/216 (5%) tumors, and affected most commonly MSH2 and MSH6.


CONCLUSIONS
This population-based series indicates that somatic MMR inactivation is a minor pathway in the development of UUC, but tumors that display defective MMR are, based on the immunohistochemical expression pattern, likely to be associated with HNPCC.
Ericson
Kajsa M
KM
Department of Oncology, University Hospital, Lund, Sweden. Kajsa.Ericson@onk.lu.se
Isinger
Anna P
AP
Isfoss
Björn L
BL
Nilbert
Mef C
MC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics; D005260:Female; D042822:Genomic Instability; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics*; D007682:Kidney Pelvis; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics; D014516:Ureteral Neoplasms / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics
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