Upper Tract Urothelial Carcinoma: A Clinicopathologic Study Including Microsatellite Instability Analysis

Abstract

Urothelial carcinoma of the renal pelvis and ureter may develop as a manifestation of the hereditary nonpolyposis colorectal cancer syndrome that is characterized by mutations in a number of DNA mismatch repair genes and detectable as microsatellite instability. In this study, we examined microsatellite instability and the clinicopathologic features of urothelial carcinoma of the renal pelvis (n ‫؍‬ 61) and ureter (n ‫؍‬ 53) from 114 consecutive patients surgically treated from 1985-1992. Clinical data were obtained through chart review. Matched normal and tumor DNA was extracted from paraffin-embedded tissue, and a panel of six microsatellite loci was analyzed. The male-female ratio was 2.8:1 with a median age of 70 years (range, 28 to 92 y). Microsatellite analysis was successful in 67 tumors, and 21 (31.3%) patients had tumors that exhibited microsatellite instability. Patients with microsatellite-unstable tumors were significantly more likely to have additional nonurologic cancers (P ‫؍‬ .015) including colorectal carcinoma (P ‫؍‬ .001) compared with patients with tumors that did not exhibit microsatellite instability. In addition, patients with microsatellite-unstable tumors showed more colorectal cancers in their family (P ‫؍‬ .026) and were more likely to have higher grade urothelial carcinoma of the upper tract (P ‫؍‬ .028). Grade and stage, but not microsatellite status, were the strongest predictors of cancer-specific survival. This study found the highest frequency of microsatellite instability in upper urothelial tract carcinomas reported to date and highlights upper tract urothelial carcinoma as a marker of the hereditary nonpolyposis colorectal cancer syndrome in some patients. These findings reinforce the importance of obtaining cancer histories in patients with upper tract urothelial carcinoma to subsequently identify individuals with the hereditary nonpolyposis colorectal cancer syndrome and at-risk relatives for surveillance and management programs.

Lynch Syndrome: A Primer for Urologists and Panel Recommendations

“…5 Microsatellite analysis in 67 consecutive UTUC tumor specimens removed from 1985 to 1992 revealed MSI in 31.3% with MSI in a Mayo Clinic study. 29 Another study using the population based Swedish cancer registry showed a 4% rate of MSI-high phenotype and a 5% loss of MMR protein on IHC with MSH2 and MSH6 mutations most commonly found. 30 An evaluation of 974 Finnish mutation carriers revealed the highest rate of urothelial tumors in MSH2 carriers (6%).…”

Genes reparadores del ADN y pronóstico en formas esporádicas de carcinoma urotelial del tracto urinario superior

“…De hecho, el 100% de estos pacientes sobreviven al año, el 90,6% (0,67-0,97) a los 3 años y el 85% (0,60-0,95) a los 5 y los 10 años, mientras que quienes muestran expresión conservada de MLH1 y PMS2 sobreviven el 82% (0,69-0,89) al año, el 65,9% (0,50-0,77) a los 3 y 5 años y el 45,6% (0,20-0,67) a los 10 años. El análisis univariante muestra que la categoría pT (OR 3,42 [1, 37]), el grado histológico (OR 5,59 [2,[6][7][8][9][10][11][12][13][14][15]15]) y la pérdida de expresión de genes MMR evaluados (OR 0,31 [0,10-0,93]) son factores que influyen en la supervivencia. Cuando el estudio multivariante considera el modelo saturado con estas 3 variables se pierde la significación estadística de la categoría pT, muy posiblemente en función de la asociación demostrada entre estadio y expresión de genes MMR.…”

Urinary tract cancer in patients with hereditary non-polyposis colorectal cancer

“…It was found that the mismatch repair deficiencydriven tumorigenesis shares many characteristics in urothelial and colorectal cancer, whereas other types of urinary tract cancer seem to follow other types of tumorigenesis [3][4][5]. This is supported by studies of HNPCC patients with cancer in the urinary tract.…”