Potential relevance of cyclooxygenase-2 expression in keratocystic odontogenic tumours - an immunohistochemical study

Abstract

There is increasing evidence that overexpression of cyclooxygenase-2 (COX-2) plays an important role in tumour growth and spread of tumours by interfering with cell proliferation, cellular adhesion, immune surveillance, apoptosis, and angiogenesis. COX-2 levels are increased in various tumours. In this study, the expression of COX-2 in 116 specimens of keratocystic odontogenic tumours (KCOT) has been analyzed. KCOT is a benign neoplasm of odontogenic origin with an occasionally aggressive behavior leading to high recurrence rates. Formalin-fixed, paraffin-embedded blocks were sectioned and used for hematoxylin-eosin (H&E) staining and incubated with an anti-COX-2 monoclonal antibody for immunohistochemical examination. Detection of the COX-2 antibody was performed with the EnVision kit. Cellular staining pattern for COX-2 was cytoplasmatic, and the staining intensities were semi-quantitatively evaluated as follows: negative (-), mild (±) or strong (+). Mild to strong expression of COX-2 was observed in 83 (71.6%) cases; 34 (29.3%) of which were mild positive and 49 (42.2%) were strong positive. COX-2 stain was detected mainly in the epithelial lining. The expression of COX-2 in KCOT and the current knowledge of the role played by COX-2 in tumorigenesis further strengthen the current concept that the KCOT should be regarded as a neoplasm. Furthermore, the multitude of markers known to be overexpressed in KCOTs is suggestive of what could be called a 'network addiction' pattern, rather than a pathological mechanism dependant on a specific activated/suppressed gene, thus explaining its aggressive behavior.

Odontogenic epithelial proliferation is correlated with COX-2 expression in dentigerous cyst and ameloblastoma

“…Mendes et al showed a distinct overexpression of COX-2 in keratocytic odontogenic tumor, and they hypothesized that they would be likely to observe a certain degree of COX-2 expression in developmental cysts such as dentigerous cysts (38,39). In addition, a previous study of 30 radicular cyst specimens demonstrated the expression of COX-2 in the lining epithelium of all 30 specimens, and reached the conclusion that COX-2 may be involved in a possible mechanism for radicular cyst pathogenesis and expansion through its effect on the production of PG and matrix metalloproteinase (40).…”

“…to proceed through the effect of SHH on the upregulation of proliferative markers such as p53 leading to the activation of the Ras/Raf/ERK cascade, which, in turn, induces the expression of COX-2 (38,43). The primary requirement for any lesion to expand within the bone is the ability to resorb the dense crystalline environment (44).…”

Investigation of clinicopathological parameters and expression of COX-2, bcl-2, PCNA, and p53 in primary and recurrent sporadic odontogenic keratocysts

“…Studies have demonstrated that cyclooxygenase-2 (COX-2) levels are elevated in various tumors, particularly those involving the gastrointestinal tract, lung, skin, urinary bladder, and prostate as well as head and neck [ 11 ]. The regulation of COX-2 expression is crucial for prostaglandin E 2 (PGE 2 ) synthesis, and its upregulation may increase the synthesis of prostaglandins (PGs), thus promoting cell proliferation and angiogenesis, and inhibiting immunosurveillance [ 12 ]. Recent studies revealed that COX-2 is also overexpressed in OKC, thus suggesting that it may be an important marker involved in the biologic behavior of the OKC [ 12 , 13 ].…”

“…The regulation of COX-2 expression is crucial for prostaglandin E 2 (PGE 2 ) synthesis, and its upregulation may increase the synthesis of prostaglandins (PGs), thus promoting cell proliferation and angiogenesis, and inhibiting immunosurveillance [ 12 ]. Recent studies revealed that COX-2 is also overexpressed in OKC, thus suggesting that it may be an important marker involved in the biologic behavior of the OKC [ 12 , 13 ]. It has also been found that COX-2 expression in OKC is significantly decreased following decompression [ 13 ] and that its expression is not correlated with clinical features of the lesion [ 12 ].…”

Proteomics profiling of keratocystic odontogenic tumours reveals AIDA as novel biomarker candidate

“…Global gene expression studies employing DNA microarrays to profile KCOT and other odontogenic lesions did not yield clinically valid biomarkers . Clinically interesting KCOT biomarkers derived so far were revealed in targeted immunohistochemical studies and, up to our knowledge, no study of KCOT lesions was performed so far on a whole proteome level that would enable identification of novel putative KCOT biomarkers.…”