Clinical, dermoscopic and immunohistochemical assessment of actinic keratoses and evaluation of the effectiveness of diclofenac therapy with immunohistochemical analysis

Abstract

Actinic keratoses (AKs) is a keratinocytic neoplasm that typically develops on the face of elderly patients. Little is known regarding the clinical, dermatoscopic and immunohistochemical assessments of AK using topical diclofenac therapy. We sought to determine these assessments and evaluate the efficacy of topical diclofenac gel in AK. In this prospective, open-label study, 44 patients with 66 AKs were treated for 12 weeks with topically applied diclofenac (3% gel in 2.5% hyaluronic acid). Immunohistopathologic analyses were performed before and after diclofenac treatment using epidermal stem cell markers such as Cytokeratin 15 (CK15), Cytokeratin 19 (CK19) and p63, in addition to proliferation markers (Bcl-2, Ki-67). Diclofenac gel was found to be effective in AK, including the hyperkeratotic type. Surprisingly, complete remission was observed at a significantly higher rate in Grade 3 lesions (p = 0.017). However, imunohistochemical and histopathologic examinations revealed that 12-week treatment periods may not be sufficient to fully cure AK. The immunohistochemical analyses revealed no change in the expression levels of CK15, CK19 and Bcl-2 following diclofenac therapy. However, the expression of Ki-67 (p = 0.042) and p63 (p = 0.030) exhibited a significant decrease after therapy. Dermatoscopy is an effective method for diagnosis of AK, and topical diclofenac sodium gel was found as an effective additional treatment modality. Since positive histopathological findings were detected in some patients even with significant remission, a 12-week treatment period should be extended even in patients presenting with positive clinical response. Importantly, anti-proliferative effects of diclofenac were demonstrated by decreased Ki-67 and p63 expression levels.

Analysis of apoptosis‐associated molecules Erythroid differentiation regulator 1, bcl‐2 and p53 in actinic keratosis after treatment with ingenol mebutate

“…[19,20] Typically, the expression of bcl-2 is described as weak to highly positive in patients with AK. [17,[19][20][21] In addition, Cayirli et al [21] found that treatment with diclofenac did not result in any significant changes in the expression of bcl-2 in AK. However, to the best of our knowledge, no studies have been conducted to observe changes in the expression of bcl-2 in epidermal keratinocytes and dermal inflammatory cells after treatment with ingenol mebutate.…”

“…Elevated expression of bcl‐2 was observed in AK . Typically, the expression of bcl‐2 is described as weak to highly positive in patients with AK . In addition, Cayirli et al .…”

“…Typically, the expression of bcl‐2 is described as weak to highly positive in patients with AK . In addition, Cayirli et al . found that treatment with diclofenac did not result in any significant changes in the expression of bcl‐2 in AK.…”

Assessment of BCL-2 expression in actinic keratosis, keratoacanthoma and seborrheic keratosis cases

“…UV causes variations in a variety of genes in many apoptosis cascades (11,22). There are many studies showing Bcl-2 expression among AK cases (23,24). A study by Thomas et al showed that typically AK cases had 35-41% weak positive Bcl-2 expression (25).…”

“…Contrary to this, Hussein et al showed high Bcl-2 expression in 73% of AK cases. This situation showed that high expression values prevent apoptotic cell death of dysplastic cells and ensure their transformation to SCC (12,23). One study showed that Bcl-2 expression was limited to the basal layer in hypertrophic and atrophic AK.…”