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. 2022 Sep 26;23(19):11351.
doi: 10.3390/ijms231911351.

Topical Treatment of Actinic Keratosis and Metalloproteinase Expression: A Clinico-Pathological Retrospective Study

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Topical Treatment of Actinic Keratosis and Metalloproteinase Expression: A Clinico-Pathological Retrospective Study

Elena Campione et al. Int J Mol Sci. .

Abstract

Actinic keratosis is an intraepithelial proliferation of atypical keratinocytes that could progress into invasive squamous cell carcinoma. Most evidence suggests an important role of the dermal matrix metalloproteinases in the progression of atypical skin epithelial lesions. We evaluated the clinical efficacy of three different therapeutic modalities (a medical device containing 0.8% piroxicam cream and 50+ sunscreen, photodynamic therapy, and ingenol mebutate gel) to treat suspicious actinic keratoses, which were biopsied for histopathological examination and then analyzed for the expression of matrix metalloproteinases by immunohistochemistry. Clinical, dermoscopic, and reflectance confocal microscopy evaluations revealed a gradual decrease in all standard scores validated for actinic keratosis assessment at the end of the treatments. From a histopathological point of view, we documented the substantial restoration of normal skin architecture, while the immunohistochemical evaluation of matrix metalloproteinases showed a reduction in expression in the treated skin lesions compared to the baseline. As actinic keratoses are considered the precursors of squamous cell carcinoma, their treatment is crucial to prevent the development of a more aggressive disease. Our study monitored the evolution of actinic keratoses subjected to three different topical therapies, with the value of correlating clinical and histopathological findings. Moreover, as the matrix metalloproteinases are largely recognized factors involved in the pathogenesis and evolution of actinic keratosis to squamous cell carcinoma, the demonstration by immunohistochemistry of a reduction in their expression after the treatments adds new valuable concern to the field.

Keywords: actinic keratosis; immunohistochemistry; ingenol mebutate; metalloproteinases; photodynamic therapy; piroxicam; topical therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Clinical, dermoscopic, and reflectance confocal microscopy evaluation before (T0) and after treatment (T1). In the panels on the left, the images represent the clinical aspects of the target lesion and the field of cancerization of the scalps of different patients treated with different therapies: (A) medical device 0.8% piroxicam and 50+ sunscreen, (B) photodynamic therapy (PDT), (C) 0.015% ingenol mebutate (IM) gel; the dermoscopic features of the target lesion, in detail; and reflectance confocal microscopy mosaic (6 × 6) aspects of the target lesion and the field of cancerization. The blue circles and arrows indicate the atypical honeycombing pattern, constituted by pleomorphic keratinocytes; the red asterisks areas of detached keratinocytes; the green arrows inflammatory infiltrate; and the yellow arrows hyper- and para-keratosis. In the panels on the right, we report the dermoscopic and reflectance confocal microscopy scores of the target lesion and the reflectance confocal microscopy scores of the field of cancerization for the respective treatments.
Figure 2
Figure 2
Histopathological features and metalloproteinase-1 and -2 expression in target lesions before (T0) and after treatment (T1). (a) The first two columns show the histopathological aspects of actinic keratoses before and after treatment with medical device 0.8% piroxicam and 50+ sunscreen, photodynamic therapy (PDT), and ingenol mebutate (IM) gel (hematoxylin–eosin, original magnification: 100×). The two central columns show images demonstrating the immunohistochemical expression of matrix metalloproteinase-1 (MMP1), while the last two show the staining for matrix metalloproteinase-2 (MMP2) in the target lesions before and after each treatment (original magnification: 100×). (b) Semiquantitative evaluation of matrix metalloproteinase expression before and after each therapeutic agent. * p < 0.01; ** p < 0.001.
Figure 3
Figure 3
Immunohistochemical evaluation of the proliferation rate of the target lesions by Ki-67 before and after treatment. Semiquantitative evaluation of Ki-67 before and after medical device 0.8% piroxicam and 50+ sunscreen, photodynamic therapy (PDT), and ingenol mebutate (IM) gel. * p < 0.01; ** p < 0.001.

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