[Molecular pathology in hereditary colorectal cancer. Recommendations of the Collaborative German Study Group on hereditary colorectal cancer funded by the German Cancer Aid (Deutsche Krebshilfe)].
Although twin studies indicate that inherited genetic factors contribute to about 35% of colorectal cancers (CRC), the exact genetic background has currently been elucidated in only 5-10% of cases. These comprise several hereditary cancer predisposition syndromes that present with a high number of syn- or metachronous neoplasms within an affected person and/or family. Many of these tumors exhibit typical histopathological changes. In general, one should discriminate between cancer syndromes associated with adenomatous and non-adenomatous (i.e., hamartomatous) polyps, the latter being quite rare. The patient's age often serves as a substantial hint to hereditary cancer. The next step of diagnostic work-up includes analysis of microsatellite instability (MSI) together with immunohistochemical detection of a loss of expression in one of the most frequently affected mismatch repair genes (MSH2, MSH6; MLH1, PMS2). Finally, the molecular demonstration of a gene mutation in the blood or germline is the most expensive and tedious procedure. This requires a signed informed consent from the patient after appropriate genetic counseling.
Rüschoff
J
J
Institut für Pathologie, Klinikum Kassel. ruesch@klinikum-kassel.de
Roggendorf
B
B
Brasch
F
F
Mathiak
M
M
Aust
D E
DE
Plaschke
J
J
Mueller
W
W
Poremba
C
C
Kloor
M
M
Keller
G
G
Muders
M
M
Blasenbreu-Vogt
S
S
Rümmele
P
P
Müller
A
A
Büttner
R
R
D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D003937:Diagnosis, Differential; D020022:Genetic Predisposition to Disease; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D012004:Rectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*