Concurrent Ki-67 and p53 immunolabeling in cutaneous melanocytic neoplasms: An adjunct for recognition of the vertical growth phase in malignant melanomas?

Ki-67 labeling of paraffin sections has been correlated with the number of cells in non-G, phases of the replicative cell cycle, and this immunohistoc hemical technique has been applied to the evaluation of a variety of human neoplasms. Similarly, immunolabeling for p53 protein has been used to detec t mutations in the corresponding gene, as a reflection of possible cellular transformation in the same context. Both of these techniques were applied to 253 melanocytic tumors of the skin to assess their possible utility in t he diagnosis and subcategorization of such lesions. They included 76 banal (common) nevi (CN), 39 Spitz nevi (SN), 62 superficial spreading malignant melanomas in radial growth (SSMMs), 32 nodular malignant melanomas (NMMs), 21 lentigo maligna melanomas in radial growth (LMMs), and 23 melanomas aris ing in association with preexisting compound nevi (MCN), One hundred cells were counted randomly in each tumor, and dark, exclusively nuclear reactivi ty was scored as positive labeling; results were recorded as percentages. N egligible Ki-67 and p53 labeling was seen in CN and SN, at a level that was similar to that obtained in cases of LMM and MCN, The largest proportion o f Ki-67-positive and p53-positive cells was observed in NMMs, followed by S SMMs, Radial growth-phase SSMMs and LMMs demonstrated immunoprofiles that w ere similar to those of melanocytic nevi, and MCN did so as well. The proto typical malignant melanocytic tumor representing the vertical growth phase- nodular melanoma-demonstrated a statistically significant difference from a ll other lesions in this study with respect to Ki-67 index (P =,008, chi(2) ) and p53 reactivity (P < .000001, chi(2)). Subsequent concurrent use of a Ki-67 threshold index of 10% and a p53 index of 5% correctly indicated the presence of vertical growth in 75% of NMMs, whereas only 8% of radial growt h phase melanomas of other types were colabeled at the same levels of react ivity for the two markers (P < .00001, chi(2)). Thus, although the distinct ion between benign and malignant melanocytic tumors could and should not be based on immunohistology for Ki-67 and p53, these results suggest that the latter determinants may, in fact, be used as an adjunct to morphology in t he recognition of the vertical growth phase in cutaneous malignant melanoma s.