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Microsatellite instability as indicator of MSH2 gene mutation in patients with upper urinary tract transitional cell carcinoma
  1. M Roupret1,2,
  2. J Catto3,4,
  3. F Coulet5,
  4. A-R Azzouzi3,4,
  5. N Amira1,
  6. T Karmouni1,
  7. G Fromont6,
  8. M Sibony7,
  9. G Vallancien6,
  10. B Gattegno1,
  11. M Meuth8,
  12. F C Hamdy3,4,
  13. O Cussenot1,2
  1. 1Department of Urology, Tenon Hospital, Paris, France
  2. 2Department of CeRePP/EA3104, University of Paris VII and University of Paris V
  3. 3Sheffield Hospital, Sheffield, UK
  4. 4Academic Urology Unit, University of Sheffield
  5. 5Department of Genetics, Tenon Hospital, Paris, France
  6. 6Institut Mutualiste Montsouris, Paris, France
  7. 7Department of Pathology, Tenon Hospital, Paris, France
  8. 8The Institute for Cancer Studies, Sheffield University Medical School, Sheffield, UK
  1. Correspondence to:
 Dr M Roupret
 Hôpital Tenon, 4 rue de la Chine, 75 020 Paris, France; mroupretclub-internet.fr

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Upper urinary tract transitional cell carcinoma (UUTTCC) accounts for 5% of all urothelial carcinomas.1 Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome predisposing to colorectal cancer that accounts for about 5% of all colorectal cancers.2 It is revealed by colorectal cancer (63%) or extracolonic cancers, most often of the endometrium (9%) or ovary, but sometimes of the upper urinary tract (5%), small bowel, stomach, or hepatobiliary tract.3–5 Patients with hereditary non-polyposis colorectal cancer have a genetic risk of developing these cancers.3,6

This study concerns patients with upper urinary tract transitional cell carcinoma who did not meet the international clinical criteria (Amsterdam criteria)5 for hereditary non-polyposis colorectal cancer. The question that arises is whether the biochemical and molecular biology tests used to screen for hereditary non-polyposis colorectal cancer might not help detect hereditary disease among these cases of upper urinary tract transitional cell carcinoma.7

The tests used in suspected cases of hereditary non-polyposis colorectal cancer are:

  • Microsatellite instability detection. Microsatellite instability is an indication that there have probably been mutations in genes encoding proteins involved in DNA repair. It is an indicator of the clonal expansion of neoplasms and was first identified in the tumours of patients with hereditary non-polyposis colorectal cancer; high microsatellite instability levels are nearly always present in these tumours.2,8–11 Microsatellite instability is found in almost 40% (39–46) of cases of upper urinary tract transitional cell carcinoma (high and low levels).12,13

  • Immunohistochemistry. Immunohistochemistry is used to evaluate loss of protein expression. Hereditary non-polyposis colorectal cancer is caused by germline mutations affecting one or several mismatch repair genes—that is, genes hMSH2 (60% of the time), hMHL1 (30%) and, more rarely, hMSH3, hPSM2, and hMSH6.2,14 Colon cancers with high …

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