DNA mismatch repair defects and microsatellite instability status in periocular sebaceous carcinoma

Anand Rajan Kd; Christopher Burris; Nicholas Iliff; Michael Grant; James R Eshleman; Charles G Eberhart

doi:10.1016/j.ajo.2013.12.002

DNA mismatch repair defects and microsatellite instability status in periocular sebaceous carcinoma

Am J Ophthalmol. 2014 Mar;157(3):640-7.e1-2. doi: 10.1016/j.ajo.2013.12.002. Epub 2013 Dec 7.

Authors

Anand Rajan Kd¹, Christopher Burris¹, Nicholas Iliff², Michael Grant², James R Eshleman¹, Charles G Eberhart³

Affiliations

¹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
² Department of Ophthalmology, Johns Hopkins University School of Medicine Wilmer Eye Institute, Baltimore, Maryland.
³ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Ophthalmology, Johns Hopkins University School of Medicine Wilmer Eye Institute, Baltimore, Maryland. Electronic address: ceberha@jhmi.edu.

PMID: 24321472
DOI: 10.1016/j.ajo.2013.12.002

Abstract

Purpose: To characterize mismatch repair protein expression and the role of DNA repair abnormalities in sebaceous carcinomas of the ocular adnexa.

Design: Retrospective case-series study.

Methods: We reviewed 10 cases of sporadic sebaceous carcinoma and 1 case involving a patient with a family history consistent with Muir-Torre syndrome. Immunohistochemistry was used to analyze the presence of 4 mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) in these tumors. DNA was extracted from 7 of the larger tumors as well as from adjacent normal control tissue and microsatellite instability (MSI) analysis using 5 highly sensitive mononucleotides and 2 pentanucleotides was performed.

Results: All 10 sporadic periocular sebaceous carcinomas maintained strong staining of the 4 mismatch repair genes, while tumor from the patient with Muir-Torre syndrome showed loss of staining for the mismatch repair genes MSH2 and MSH6. MSI testing of 7 tumors identified no changes in sporadic cases and yielded results supporting presence of repeat sequence instability in the Muir-Torre-associated case.

Conclusions: Sporadic sebaceous carcinoma of the ocular adnexa is not commonly associated with a loss of mismatch repair genes or microsatellite instability.

Publication types

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

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Adenocarcinoma, Sebaceous / genetics*
Adenocarcinoma, Sebaceous / metabolism
Adenocarcinoma, Sebaceous / pathology
Adenosine Triphosphatases / genetics
Adenosine Triphosphatases / metabolism
Adult
Aged
Aged, 80 and over
DNA Mismatch Repair / genetics*
DNA Repair Enzymes / genetics
DNA Repair Enzymes / metabolism
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Eyelid Neoplasms / genetics*
Eyelid Neoplasms / metabolism
Eyelid Neoplasms / pathology
Female
Humans
Immunoenzyme Techniques
Male
Microsatellite Instability*
Middle Aged
Mismatch Repair Endonuclease PMS2
MutL Protein Homolog 1
MutS Homolog 2 Protein / genetics
MutS Homolog 2 Protein / metabolism
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Retrospective Studies
Sebaceous Gland Neoplasms / genetics*
Sebaceous Gland Neoplasms / metabolism
Sebaceous Gland Neoplasms / pathology

Substances

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