Altered expression of hMLH1 and hMSH2 protein in endometrial carcinomas with microsatellite instability

Citation
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
Journal title
HUMAN PATHOLOGY
ISSN journal
00468177 → ACNP
Volume
31
Issue
3
Year of publication
2000
Pages
354 - 358
Database
ISI
SICI code
0046-8177(200003)31:3<354:AEOHAH>2.0.ZU;2-F
Abstract
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.