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The utility of p16 immunostaining in cutaneous keratinocytic lesion
Med Biol Sci Eng 2019;2(2):40-45
Published online July 31, 2019
© 2019 Medical Biological Science and Engineering.

Ran Hong

Department of Pathology, College of Medicine, Chosun University, Gwangju, Korea
Correspondence to: Ran Hong
Department of Pathology, College of Medicine, Chosun University, 365, Philmundae-ro, Dong-gu, Gwangju 61453, Korea
Tel: +82-62-230-6356
Fax: +82-62-226-5860
Received January 23, 2019; Revised February 13, 2019; Accepted February 13, 2019.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Several kinds of atypical keratinocytic lesions including seborrheic keratosis (SK), actinic keratosis (AK), Bowen’s disease (BD) and squamous cell carcinoma (SqCC) are common lesion in pathologic practice. While most of them show characteristic histological feature, occasionally we meet the diagnostic difficulty by overlapping or mixed histologic features. The aim of this study was to evaluate the immunostaining pattern of p16 (INK4a) in SK, AK, BD and SqCC, and identify the utility of p16 immunohistochemical staining in differential diagnosis of above cutaneous keratinocytic lesions. We studied 50 cases of keratinocytic lesions (20 examples of SK and 10 cases of each of AK, BD and SqCC). The cases were stained for p16. Ninety percent of BD cases showed strong block-positivity and typical SK not show reactivity with p16, just only one case showed patch staining pattern. In AK, only one case showed block-positivity and another cases showed patchy staining pattern. In SqCC, only 3 out of 10 cases showed strong staining pattern. This study demonstrated that the expression of p16 is strongly associated with the progression of BD (p<0.001). This staining pattern was not seen in AK and SK. Accordingly, immunohistochemistry for p16 is a useful test in the differential diagnosis of intra-epidermal atypical keratinocytic lesion. However, despite the statistical significance (p<0.001), our small series suggests that as not all typical cases of BD are positive with p16, negative p16 staining alone cannot be used to classify atypical keratinocytic lesions, and the finding of hematoxylin and eosin staining remains paramount.
Keywords : p16; Immunohistochemistry; Skin; Keratinocyte; Bowen disease
  1. Bloch PH. Transformation of seborrheic keratosis into Bowen’s disease. J Cutan Pathol 1978;5:361-7.
    Pubmed CrossRef
  2. Monteagudo JC, Jorda E, Terencio C, Llombart-Bosch A. Squamous cell carcinoma in situ (Bowen’s disease) arising in seborrheic keratosis: three lesions in two patients. J Cutan Pathol 1989;16:348-52.
    Pubmed CrossRef
  3. Weedon D. Weedon’s skin pathology. 3rd ed. Brisbane: Elsevier;2010.
  4. Harvey NT, Leecy T, Wood BA. Immunohistochemical staining for p16 is a useful adjunctive test in the diagnosis of Bowen’s disease. Pathology 2013;45:402-7.
    Pubmed CrossRef
  5. Blokx WA, de Jong EM, de Wilde PC, Bulten J, Link MM, Ruiter DJ, et al. P16 and p53 expression in (pre)malignant epidermal tumors of renal transplant recipients and immunocompetent individuals. Mod Pathol 2003;16:869-78.
    Pubmed CrossRef
  6. Negri G, Vittadello F, Romano F, Kasal A, Rivasi F, Girlando S, et al. p16INK4a expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri. Virchows Arch 2004;445:616-20.
    Pubmed CrossRef
  7. Conscience I, Jovenin N, Coissard C, Lorenzato M, Durlach A, Grange F, et al. P16 is overexpressed in cutaneous carcinomas located on sun-exposed areas. Eur J Dermatol 2006;16:518-22.
  8. Horn LC, Reichert A, Oster A, Arndal SF, Trunk MJ, Ridder R, et al. Immunostaining for p16INK4a used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia. Am J Surg Pathol 2008;32:502-12.
    Pubmed CrossRef
  9. Tam SW, Shay JW, Pagano M. Differential expression and cell cycle regulation of the cyclin-dependent kinase 4 inhibitor p16Ink4. Cancer Res 1994;54:5816-20.
  10. Willman JH, Heinz D, Golitz LE, Shroyer KR. Correlation of p16 and pRb expression with HPV detection in Bowen’s disease. J Cutan Pathol 2006;33:629-33.
    Pubmed CrossRef
  11. Nilsson K, Svensson S, Landberg G. Retinoblastoma protein function and p16INK4a expression in actinic keratosis, squamous cell carcinoma in situ and invasive squamous cell carcinoma of the skin and links between p16INK4a expression and infiltrative behavior. Mod Pathol 2004;17:1464-74.
    Pubmed CrossRef

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