Immunohistochemical expression of DNA mismatch repair (MMR) system proteins (hMLH1, hMSH2) in cervical preinvasive and invasive lesions.
The purpose of our study was to analyze the immunohistochemical expression of two MMR system proteins at different steps of neoplastic progression within the squamous cervical epithelium. We compared cases showing normal histologic appearance with those affected by low and high-grade squamous intraepithelial lesions and invasive cervical carcinoma. We investigated formalin-fixed and paraffin-embedded tissue specimens obtained from 83 selected patients (55 with preinvasive neoplastic lesions and 28 with invasive squamous cervical carcinoma) for the expression of hMSH2 and hMLH1 at the immunohistochemical level. We also included 30 patients with histologically normal cervix as a control group. Epithelial cells of CIN lesions showed a significant increase in the expression of both hMLH1 and hMSH2 proteins compared to non-neoplastic squamous epithelium (p < 0.0001). The cases of invasive carcinoma showed a positivity for hMLH1 protein that was statistically lower than that for non-neoplastic cells (p = 0.0009) and that for cases with CIN (p < 0.0001). Positivity for hMSH2 protein was higher than that for normal epithelium (p = 0.0007), but lower than that for preinvasive lesions (p = 0.0001). Preinvasive lesions showed increased expression of both proteins if compared with normal esocervical epithelium. Neoplastic stromal invasiveness is associated with a significant loss of hMLH1 function.
Ciavattini
Andrea
A
Institute of Obstetrics and Gynecology, Politechnical University of Marche, Italy. andreac@univpm.it
Piccioni
Marco
M
Tranquilli
Andrea Luigi
AL
Filosa
Alessandra
A
Pieramici
Tiziana
T
Goteri
Gaia
G
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D020137:Base Pair Mismatch; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein