(2004) Microsatellite instability as indicator of MSH2 gene mutation in patients with upper urinary tract transitional cell carcinoma

Blogger's Note: more recent research can be found on this blog (eg. Lynch Syndrome/UUTC) including 2 recent (posted Sept 2012) research papers; European Guidelines/Mount Sinai, Toronto

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 Microsatellite instability as indicator of MSH2 gene mutation in patients with upper urinary tract transitional cellcarcinoma

"Upper urinary tract transitional cell carcinoma was never the first cancer in their personal history."

Key points

Hereditary non-polyposis colorectal cancer (HNPCC) is
an autosomal dominant syndrome predisposing to
colorectal cancer which 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%).

Our aim was: (a) to establish the benefits of routine
screening for microsatellite instability in patients with
upper urinary tract transitional cell carcinoma
(UUTTCC) who did not meet the Amsterdam criteria
for hereditary non-polyposis colorectal cancer, (b) to
establish selection criteria for patients in whom testing
for germline mutation of the MSH2 repair gene should
be performed.

164 patients treated for sporadic upper urinary tract
transitional cell carcinoma were screened for microsatellite
instability. Twenty seven patients had high
microsatellite instability levels. For those patients, we
collated clinical data, and performed immunohistochemistry
to investigate loss of hMSH2 protein and PCR
single strand conformation polymorphism gene
sequence analysis to detect hMSH2 mutations.

The presence of a mutation was significantly related
to (a) a history of a HNPCC associated cancer
(p = 0.038), (b) the occurrence of upper urinary tract
transitional cell carcinoma before 60 years of age
(p = 0.04), and (c) the indication by loss of protein
expression on immunohistochemistry.

In cases of upper urinary tract transitional cell
carcinoma with high microsatellite instability levels,
hereditary predisposition should be investigated if the
patient has a history of a HNPCC associated cancer or
is under 60. Patients with hMSH2 protein loss on
immunohistochemistry should undergo testing for a
germline mutation.