title: 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.
authors: Dermatology Services, Ağrı Military Hospital, Ağrı, Turkey.
authors: Mutlu
authors: M
authors: Çayirli
authors: Osman
authors: O
authors: Köse
authors: Murat
authors: M
authors: Demiriz
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016009:Chi-Square Distribution; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D046169:Dermoscopy; D004008:Diclofenac / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005782:Gels; D006801:Humans; D007150:Immunohistochemistry; D053569:Keratin-15 / Q000378:metabolism; D053539:Keratin-19 / Q000032:analysis; D055623:Keratosis, Actinic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012074:Remission Induction; D012720:Severity of Illness Index; D012867:Skin / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D014421:Turkey
chemical_list: D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D005782:Gels; C116015:KRT15 protein, human; D053569:Keratin-15; D053539:Keratin-19; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D004008:Diclofenac