Oral and maxillofacial pathology
Participation of hMLH1, p63, and MDM2 proteins in the pathogenesis of syndromic and nonsyndromic keratocystic odontogenic tumors

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Objectives

To evaluate the expression of hMLH1, p63, and MDM2 in Gorlin syndrome–associated keratocystic odontogenic tumors (SKOTs) and nonsyndromic keratocystic odontogenic tumors (NSKOTs).

Study Design

Seventeen primary NSKOTs, 17 SKOTs, and 8 recurrent NSKOTs were analyzed by using immunohistochemistry.

Results

No significant differences in the hMLH1, p63, or MDM2 labeling indices were observed between groups (P = .398; P = .232; P = .426, respectively). Higher hMLH1 immunoexpression was found in the basal layer of primary NSKOTs. Most KOTs exhibited p63 immunoexpression in the upper layers of the epithelium. MDM2 immunoexpression was observed in the upper epithelial layers of SKOTs and recurrent NSKOTs.

Conclusion

It was not possible to correlate the immunoexpression of hMLH1, p63, and MDM2 in SKOTs and primary and recurrent NSKOTs, suggesting that these proteins exert independent effects on the development of these groups of tumors.

Section snippets

Materials and Methods

The study was approved by the Ethics Committee of the Federal University of Rio Grande do Norte (UFRN), Natal, Brazil (No. 246.800). Seventeen cases of primary NSKOTs, 17 cases of SKOTs, and 8 cases of recurrent NSKOTs were retrieved from the archives of the Pathological Anatomy Services of the Departments of Oral Pathology of UFRN and University of Fortaleza (UNIFOR) for the period between January 2005 and December 2012. The number of available institutional archival cases defined the size of

Results

Immunoexpression of hMLH1 in the epithelial component of KOT was positive in all cases analyzed. In primary NSKOT, immunostaining for hMLH1 was observed mainly in the basal epithelial layer (58.5%; n = 10). In SKOT and recurrent NSKOT, immunostaining was found in all layers of the epithelium, with no predominance in a specific layer. The median hMLH1 labeling index in the lining epithelium was 52.2 (range: 12.1-75.5) in the group of primary NSKOT, 56.9 (range: 23.3-69.7) in SKOT, and 41.2

Discussion

The MMR repair system is important for maintaining genomic stability, reducing DNA errors, and preventing these errors from becoming fixed mutations during cell proliferation. MMR deficiencies are associated with a higher risk of development of different types of cancer.25 Immunohistochemical analysis of the expression of the hMSH2 and hMLH1 genes in tumors indicates that the expression of these genes is typically lost in patients with hereditary nonpolyposis colorectal cancer.13, 14

Although

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