Ki-67 and p53 Expression in Minimal Deviation Melanomas as Compared with Other Nevomelanocytic Lesions

Abstract

Minimal deviation melanoma is a controversial entity encompassing a heterogeneous group of lesions cytologically in the spectrum between recognized subtypes of nevi and conventional "primary configuration" melanomas and reported to have a better prognosis than the latter. To evaluate the distinctiveness of minimal deviation melanoma, Ki-67 proliferation rates and p53 expression in minimal deviation melanomas were compared with those in compound nevi, Spitz nevi, and vertical growth phase superficial spreading malignant melanoma. Twelve examples of each lesion were immunostained with antibodies to the Ki-67 and p53 proteins and evaluated by a pathologist who was blind to the diagnoses. The mean Ki-67 (MIB-1) proliferation rates for the compound nevi, Spitz nevi, minimal deviation melanomas, and superficial spreading malignant melanomas were 0, 3%, 13%, and 25%, respectively. The mean Ki-67 proliferation rate was statistically greater in the minimal deviation melanomas than in the compound nevi or the Spitz nevi (P < .05), but the proliferation rates in the two melanoma subtypes were not statistically significant (P ‫؍‬ .08). The mean p53 values for these lesions were 0, 9%, 9%, and 26%, respectively; the latter two were statistically different (P < .01). Based on these Ki-67 and p53 immunophenotypes, minimal deviation melanoma may represent a distinct entity. In a busy dermatopathology practice, there are seen rare and unusual forms of nevomelanocytic proliferations that do not conform to generally recognized nevus or melanoma classifications. Placement of these problematic lesions into benign or malignant categories is difficult, and terms such as melanocytic tumor of undetermined malignant potential (1) or atypical melanocytic proliferation have been developed to communicate this prognostic uncertainty. Along these lines, the classification of minimal deviation melanoma (2) was developed for a subset of such tumors, composed of a monotonous cell population, that were more atypical than ordinary nevi but less atypical than conventional melanomas. A minimal deviation melanoma architecturally consists of an expansive nodule in the vertical growth phase that fills the papillary dermis and often extends into the reticular dermis (Fig. 1). The tumors are further classified, based on the cytologic characteristics, into subtypes such as a Spitz variant, a halo nevus-like variant, a pigmented spindle cell variant, a desmoplastic variant, a small cell variant, and a dermal variant. Minimal deviation melanomas have been associated with a better prognosis (2). As with other attempts to deal with these rare and difficult melanocytic neoplasms, this classification remains controversial (3) and has not been uniformly accepted in the dermatopathology community. This study seeks to evaluate the distinctiveness of minimal deviation melanoma by comparing Ki-67 proliferation rates and p53 expression in minimal deviation melanomas with those in compound

Immunohistochemical characteristics of melanoma

“…[55][56][57][58][59][60][61][62] Ki-67 staining has been shown in multiple studies to be positive in ,5% of tumor cells in most benign nevi, although there have been reports of up to 15% positivity in Spitz and dysplastic nevi. 55,56,57,59,[63][64][65][66] Conversely, Ki-67 staining is reported as positive in 13-30% of the cells in a malignant melanoma, although individual cases can show almost 100% nuclear positivity. 55,56,58,59,[63][64][65][66] There have been mixed results using Ki-67 as a prognostic marker in malignant melanoma.…”

Unusual variants of malignant melanoma

“…62 The distinction of a minimal-deviation melanoma arising in a congenital nevus from the proliferation nodule of a congenital nevus may be difficult. There is little difference architecturally, as both manifest a nodular pattern of growth that results in distortion of the dermal silhouette.…”

Molecular pathways supporting the proliferation staging of malignant melanoma (Review)

“…Overexpression of p53 has been shown in MM originating from a precursor p53-negative melanocytic nevus (50). Some melanocytomas show about 10% cell positivity for p53 protein (52). A correlation was reported between p53 expression and the increased MM thickness (53).…”