Expression of CREB in Primary Pterygium and Correlation with Cyclin D1, ki-67, MMP7, p53, p63, Survivin and Vimentin

Abstract

Aim: Ultraviolet (UV) B irradiation induces gene expression that leads to skin cancer. Among the transcription factors induced by UVB radiation exposure, the cyclic AMP response element-binding protein (CREB) is significant. Since several factors downstream of CREB signaling are known to be involved in pterygium pathogenesis, we investigated CREB expression in pterygial and human conjunctival tissues to evaluate if a similar expression pattern is present. Moreover, we analyzed the correlation with CREB expression and other known pterygium markers. Methods: Primary pterygium samples and normal bulbar conjunctivas surgically removed were analyzed. Formalin-fixed, paraffin-embedded tissues were stained by immunohistochemistry with anti-CREB, anti-vimentin, anti-ki-67, anti-survivin, anti-MMP7, anti-p63, anti-cyclin D1, or anti-p53 antibodies. Results: 94.4% of pterygium samples were positive for CREB with a significant difference compared to the control group (p = 0.002). The staining was localized in the epithelium and absent in the stroma. An increased expression was found for cyclin D1 (p = 0.019), ki-67 (p = 0.005), vimentin (p = 0.003), survivin (p < 0.001), p63 (p = 0.003), and MMP7 (p = 0.002). CREB expression showed a significant correlation with cyclin D1 (ρ = 0.49; p = 0.035), ki-67 (ρ = 0.61; p = 0.007), and p53 (ρ = 0.57; p = 0.013) in pterygium. Conclusions: These results permit to hypothesize that CREB is involved in pterygium pathogenesis. Since various molecules have been discovered to inhibit CREB, these data could be of interest for pterygium treatment.

The role of ultraviolet radiation in the pathogenesis of pterygia (Review)

“…Previous studies have indicated that pterygium is associated with numerous risk factors, including ultraviolet (UV) radiation (2)(3)(4)(5), viral infection (6)(7)(8), hereditary factors (9)(10)(11), immunological factors (12), aseptic inflammation (13), environmental irritation from wind, dust or trauma, smoke and ocular dryness (14). Recently, increased levels of the transcription factors cAMP response element-binding protein (15), cytochrome P450 1A1 protein (16), phospholipase D (17), and aquaporin-1 and -3 (18) have been implicated as risk factors for pterygia development. UV radiation remains a well-established pathogenic factor of pterygium based on epidemiological evidence (19)(20)(21).…”

Analysis of Recurrence Patterns Following Pterygium Surgery With Conjunctival Autografts

“…The tumor-like characteristics of pterygium are expressed when reproliferation occurs after excisional surgery. 9 , 10 Although various surgical procedures, including adjunctive treatments, have been proposed for the treatment of pterygium, recurrence remains a significant problem after surgical excision. 11 – 13 …”

Pterygium recurrence and corneal stabilization point after pterygium excision using the controlled partial avulsion fibrin glue technique

“…[1][2][3] Because of these characteristics, pterygium was previously considered a degenerative disorder. However, recent studies have proven that pterygium also has proliferative histological characteristics, [4][5][6][7][8][9] such as mild dysplasia, local invasiveness, and abnormal p53 gene expression, and clinical features, including a high recurrence rate following pterygium excision.…”

“…However, recent studies have proven that pterygium also has proliferative histological characteristics, such as mild dysplasia, local invasiveness, and abnormal p53 gene expression, and clinical features, notably a high recurrence rate following excision. [4][5][6][7][8][9] The primary treatment for pterygium is surgical excision. Indeed, over the last two decades, several new approaches in surgical techniques have been proposed and promising success rates have been obtained.…”