p16 Expression Is Lost in Severely Atypical Cellular Blue Nevi and Melanoma Compared to Conventional, Mildly, and Moderately Atypical Cellular Blue Nevi

Abstract

Background. Significant decreases in p16 expression have been shown to occur in melanoma compared to Spitz tumors, and loss of p16 staining has been found to correlate with melanoma tumor progression. However, comparison of p16 between atypical cellular blue nevi (CBN) and melanoma has not been reported previously. Methods. p16 immunohistochemical staining was evaluated in 14 atypical CBN, 8 conventional and atypical melanocytic nevi, and 16 melanomas, including 4 malignant CBN. p16 staining intensity was graded on a scale of 0-3 and the percentage of melanocytes stained with p16 was determined. Results. p16 staining was significantly higher in all CBN as a group when compared to melanomas (P = 0.001) and malignant CBN (P = 0.00008). Higher p16 expression was also seen in mildly (P = 0.0002) and moderately atypical (P = 0.02), but not severely atypical, CBN compared to melanomas. Conclusions. p16 immunohistochemical expression is higher in mildly and moderately atypical CBN compared to severely atypical CBN and melanomas. In conjunction with additional markers and histology, p16 staining may be useful in confirming the benign nature of these tumors, but is not useful in distinguishing severely atypical CBN from malignant cases, consistent with the overlapping histologic features between these tumors.

Figure 1

p16 staining intensity (a) and percentage of melanocytes stained with p16 (b) and Ki-67 (c) in conventional benign and atypical nevi, CBN, melanoma, and malignant CBN. (a, b) p16 staining was higher in all CBN when compared to melanoma (P = 0.02 and P = 0.001) and malignant CBN (P = 0.02 and P = 0.00008). Upon subclassifying the CBN based on degree of atypia, a significant increase in p16 staining in benign/mildly atypical CBN (P = 0.0002) and moderately atypical CBN (P = 0.02) but not severely atypical CBN was found compared to melanoma. Similar results were obtained when comparing these classes of CBN with malignant CBN. Compared to conventional nevi, benign/mildly and moderately atypical CBN had similar p16 staining, but a significant decrease in p16 was found in severely atypical CBN (P = 0.04). (c) Ki-67 was significantly lower in CBN of all levels of atypia compared to melanoma (P < 0.03).

Figure 2

H and E and p16 staining of representative conventional CBN, mildly atypical CBN, severely atypical CBN, and a melanoma (metastatic) mimicking CBN. p16 staining intensity: benign CBN = 3, mildly atypical CBN = 3, severely atypical CBN = 1, and melanoma = 0.