F. Paraf et al., MLH1 and MSH2 protein immunohistochemistry is useful for detection of hereditary non-polyposis colorectal cancer in young patients, HISTOPATHOL, 39(3), 2001, pp. 250-258
Citations number
66
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Aims: Hereditary non-polyposis colorectal cancer is related to germline mut
ations of DNA mismatch repair genes MLH1 and MSH2, which result in microsat
ellite instability and loss of protein expression of the corresponding muta
ted gene in the tumour tissue.
Methods and results: MLH1 and MSH2 protein expression was studied by immuno
histochemistry in paraffin-embedded surgical samples of 100 colorectal aden
ocarcinomas occurring before 50 years of age. Absence of tumour cell nuclea
r staining with positive internal control (normal mucosa, lymphoid follicle
s) was considered negative. Loss of MLH1 or MSH2 expression was found in 20
cases with microsatellite instability in 15 cases. Twelve of these patient
s had a family history of colorectal cancer. Compared with MLH1- and MSH2-p
ositive cases, MLH1 or MSH2-deficient colorectal adenocarcinomas were signi
ficantly associated on multivariate analysis with a younger age (38 vs. 43
years, P=0.0224), a larger tumour size (60 +/-6 vs. 46 +/-2 mm, P=0.0291),
an expanding margin (85% vs. 51%, P=0.0159), a higher number of tumour-infi
ltrating lymphocytes assessed by CD3 immunostaining (202 +/- 48 vs. 33 +/-4
CD3+ lymphocytes/10 high-power Fields, P=0.0039), and a grade 2 Crohn's li
ke lymphoid reaction (70% vs. 9%, P=0.0037). The two groups were not differ
ent for tumour site, differentiation, pTNM stage, vascular and perineural i
nvasion, peripheral adenomatous residue, and 5-year survival rates.
Conclusions: MLH1- or MSH2-deficient colorectal carcinomas of young patient
s exhibit pathological and molecular features similar to hereditary nonpoly
posis colorectal cancer. This suggests that MLH1 and MSH2 immunohistochemis
try is valuable for detecting hereditary non-polyposis colorectal cancer in
young patients.