A. Staebler et al., Altered expression of hMLH1 and hMSH2 protein in endometrial carcinomas with microsatellite instability, HUMAN PATH, 31(3), 2000, pp. 354-358
Citations number
29
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Microsatellite instability (MI) has been observed in approximately 20% of p
resumably sporadic cases of uterine endometrioid carcinoma (UEC). A previou
s mutational analysis of the 4 known DNA mismatch repair genes (hMSH2, hMLH
1, hPMS1, and hPMS2) on a small number of MI-positive tumors detected mutat
ions in only 2 of 8 cases, both in hMSH2. To further explore the underlying
cause of MI in UEC, we analyzed the protein expression of hMSH2 and hMLH1
in UEC of known MI status. Formalin-fixed, paraffin-embedded archival tissu
e from 21 UECs was analyzed by immunoperoxidase staining with monoclonal an
tibodies against hMLH1 and hMSH2 protein. Tumors were evaluated for presenc
e of nuclear staining by 3 investigators. Lack of nuclear hMLH1 staining wa
s found in 7 of 13 carcinomas with MI, but in none of 8 carcinomas without
MI (Fischer's exact, 0.018), Lack of nuclear hMSH2 staining was found in 3
of the MI-positive cases, but none of the MI-negative cases (not statistica
lly significant). Taken together, lack of nuclear staining of either hMLH1
or hMSH2 was found in 9 of 13 cases with MI and in none of 8 cases without
MI (Fischer's exact, 0.005), We conclude that MI in sporadic UEC appears to
be associated with lack of expression of either hMLH1 or hMSH2, suggesting
that inactivation of these genes may be responsible for MI in most MI-posi
tive sporadic UECs. Copyright (C) 2000 by W.B. Saunders Company.