Analysis of p53 and bcl‐2 protein expression in the non‐tumorigenic, pretumorigenic, and tumorigenic keratinocytic hyperproliferative lesions

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Abstract
The hyperproliferative keratinocytic lesions encompass a wide range of non-tumorigenic, pretumorigenic, and tumorigenic conditions. The aim of this work was to examine the expression patterns of apoptosis-linked molecules (bcl-2 and p53) in these lesions. Immunoperoxidase staining methods were applied to analyze p53 and bcl-2 protein expression in a total of 66 cases, including 12 squamous cell carcinomas (both in situ and invasive SCC), 11 actinic keratoses (AK), 13 psoriasis vulgaris (PV), eight verruca vulgaris (VV), six chronic dermatitis (CD), five seborrheic keratosis (SK), four lichen planus (LP), three epidermodysplasia verruciformis (EDV), two condyloma acuminata (CA), two lichen simplex chronicus (LSC), and 10 specimens from normal skin. As compared to normal skin (0.70 +/- 0.26), the bcl-2 average weighted scores in the non-tumorigenic (0.76 +/- 0.16), pretumorigenic (1.45 +/- 0.28), and tumorigenic lesions (2.83 +/- 0.50 and 2.92 +/- 0.50 for in situ and invasive SCC, respectively) showed significant up-regulation (p = 0.001). In the non-tumorigenic lesions, the bcl-2 expression values decreased in the following order: SK > EDV > CD > LP > CA > PV > VV (1.40 +/- 0.24 > 1.33 +/- 0.67 > 0.83 +/- 0.40 > 0.67 +/- 0.21 > 0.50 +/- 0.20 > 0.46 +/- 0.22 > 0.13 +/- 0.01, respectively). As compared to normal skin (1.10 +/- 0.23), the p53 average weighted scores in the non-tumorigenic (1.86 +/- 0.18), pretumorigenic (3.64 +/- 0.53), and tumorigenic lesions (5.00 +/- 1.00 and 5.08 +/- 0.86 for in situ and invasive SCC, respectively) showed significant up-regulation (p = 0.021). In the non-tumorigenic lesions, p53 average weighted scores decreased in the following order: SK > PV > CA > LP > CD > VV > EDV (3.20 +/- 0.49 > 2.38 +/- 0.27 > 2.0 +/- 0.0 > 1.83 +/- 0.48 > 1.0 +/- 0.37 > 1.0 +/- 0.33 > 1.0 +/- 0.0, respectively). There was a positive correlation between bcl-2 and p53 protein expression in normal skin (r = 0.966, p = 0.0001), non-tumorigenic (r = 0.775, p = 0.0001), pretumorigenic (r = 0.830, p = 0.001), and tumorigenic lesions (r = 0.757, p = 0.003). Bcl-2 and p53 proteins are altered in the keratinocytic hyperproliferative lesions. Determination of whether these alterations reflect underlying gene mutations will require further investigations.