Evaluation of Invasive Squamous Cell Carcinoma, Seborrheic Keratosis and Verruca Vulgaris in Superficial Shave Biopsies using p16, p53, p63, and PHLDA1 Immunohistochemistry

Abstract

Occasionally, the distinction between malignant and benign is challenging in superficial shave biopsies of squamoproliferative lesions. This phenomenon is compounded by the increasing prevalence of conditions encountered that weaken the immune system, such as chemotherapy, immune deficiency diseases, and antirejection medications for organ transplantation that have all been shown to increase the risk of the development of squamous cell carcinoma. We collected 30 cases (10 invasive SCC, 10 SK and 10 VV) and performed immunohistochemical staining using a panel approach composed of markers important for proliferation and the cell cycle, including Ki-67, p16, p53, and PHLDA1. The results demonstrate that the invasive SCC group was enriched for high PHLDA1 (80% with PHLDA1 score=3, 100% with PHLDA1 score ≥ 2) and high p53 (50% of SCC with p53 score ≥ 2 vs. 60% of SK and 90% of VV with p53 score=1). The SK group was enriched for low p16 (100% with p16 score ≤ 1) and high p63 scores (100% with p63 score=3). A panel approach may be utilized to help in the distinction between benign keratoses and carcinoma and may be increasingly critical to promote quality care.

The diagnostic value of p63, p16, and p53 immunohistochemistry in distinguishing seborrheic keratosis, actinic keratosis, and Bowen's disease

“…In our study, 13.3% of SK cases were negative with p16. Other studies found this percentage to be between 35% and 83%, in which the most common patterns were scattered patches of positive cells 9,13‐15 . One study has shown a connection between the intensity of p16 expression and the number of a patient's SK lesions 16 .…”

“…Delta Np63 is the most common isoform that is normally expressed in the nuclei of epidermal keratinocytes, hair follicle external root sheaths, and hair matrix germinative cells. 8,9 With increasing cell maturation, expression of delta Np63 is reduced. 10 p16INK4a is a product of the cyclin-dependent kinase inhibitor 2A gene (CDKN2A).…”

“…The p63 belongs to the p53 family of transcription factors. Delta Np63 is the most common isoform that is normally expressed in the nuclei of epidermal keratinocytes, hair follicle external root sheaths, and hair matrix germinative cells 8,9 . With increasing cell maturation, expression of delta Np63 is reduced 10 .…”

The Correlation between Human papillomavirus and Increased Expression of p53 in Seborrheic Keratosis

“…A study by Brown reported that of 10 seborrheic keratosis samples evaluated for p53 with immunohistochemistry examination, 6 samples (60%) were positive (+), and 4 samples (40%) were positive (++). 22 Another study by Ko reported that of 10 evaluated seborrheic keratoses, the mean value of p53 protein expression was 2.1. This study grouped the value of p53 into 3 sections, 1 if p53 was found in less than 10% cells, 2 if p53 was found between 10%-30% cells, and 3 if p53 was found in more than 30% cells.…”

“…In this study, the p53 protein expression was positive in all seborrheic keratosis lesions and some even exhibit an increase in p53 expression. 22 In the pathogenesis of skin malignancy, HPV plays its part in the early phases of malignancy and acts as a co-carcinogen with ultraviolet (UV) rays by aggravating DNA damage. Thus, HPV is abundantly found in pre-malignant lesions as well as benign skin tumors.…”