MutSα and MutLα immunoexpression analysis in diagnostic grading of oral epithelial dysplasia and squamous cell carcinoma

M Jessri; A J Dalley; C S Farah

doi:10.1016/j.oooo.2014.06.017

MutSα and MutLα immunoexpression analysis in diagnostic grading of oral epithelial dysplasia and squamous cell carcinoma

Oral Surg Oral Med Oral Pathol Oral Radiol. 2015 Jan;119(1):74-82. doi: 10.1016/j.oooo.2014.06.017. Epub 2014 Sep 28.

Authors

M Jessri¹, A J Dalley², C S Farah³

Affiliations

¹ The University of Queensland, UQ Centre for Clinical Research, Herston, QLD 4029, Australia; The University of Queensland, School of Dentistry, Brisbane, QLD 4000, Australia.
² The University of Queensland, UQ Centre for Clinical Research, Herston, QLD 4029, Australia.
³ The University of Queensland, UQ Centre for Clinical Research, Herston, QLD 4029, Australia; The University of Queensland, School of Dentistry, Brisbane, QLD 4000, Australia. Electronic address: camile@oralmedpath.com.au.

PMID: 25446502
DOI: 10.1016/j.oooo.2014.06.017

Abstract

Objectives: This study explored the expression of DNA mismatch repair (MMR) proteins in a range of oral biopsies. We further evaluated the significance of MMR protein expression combined with basic demographic data in differentiating grades of oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC).

Study design: Immunohistochemical expression of MutSα (hMLH1 and hPMS2) and MutLα (hMSH2 and hMSH6) were compared in 98 formalin-fixed paraffin embedded oral biopsies: 21 normal, 24 mild-dysplasia (MD), 8 moderate-to-severe-dysplasia (SD), and 45 OSCC.

Results: Expression of hMLH1, hPMS2, and hMSH2 was reduced in MD, SD, and OSCC compared with the normal. Reduced hMSH2 immunoreactivity discriminated poorly differentiated OSCC from well-differentiated OSCC. The diagnostic model correctly classified 71.4% of cases and revealed that hPMS2-negative biopsies were more likely to be cancerous (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.000-0.813; P = .040).

Conclusion: The results suggested a diagnostic role for MMR proteins in OED and OSCC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism
Adenosine Triphosphatases / metabolism
Adolescent
Adult
Aged
Biopsy
Carcinoma in Situ / metabolism*
Carcinoma in Situ / pathology
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / pathology
DNA Mismatch Repair
DNA Repair Enzymes / metabolism*
DNA-Binding Proteins / metabolism
Female
Humans
Immunohistochemistry
Male
Middle Aged
Mismatch Repair Endonuclease PMS2
Mouth Neoplasms / metabolism*
Mouth Neoplasms / pathology
MutL Protein Homolog 1
MutL Proteins
MutS DNA Mismatch-Binding Protein / metabolism*
MutS Homolog 2 Protein / metabolism
Neoplasm Grading
Nuclear Proteins / metabolism
Precancerous Conditions / metabolism*
Precancerous Conditions / pathology
Sex Factors

Substances

Adaptor Proteins, Signal Transducing
DNA-Binding Proteins
MLH1 protein, human
MutLalpha protein, human
Nuclear Proteins
Adenosine Triphosphatases
PMS2 protein, human
MSH2 protein, human
Mismatch Repair Endonuclease PMS2
MutL Protein Homolog 1
MutL Proteins
MutS DNA Mismatch-Binding Protein
MutS Homolog 2 Protein
DNA Repair Enzymes