Comparison of pHH3, Ki-67, and Survivin Immunoreactivity in Benign and Malignant Melanocytic Lesions

Abstract

Differentiating malignant melanoma from benign melanocytic lesions can be challenging. We undertook this study to evaluate the use of the immunohistochemical mitosis marker phospho-Histone H3 (pHH3) and the proliferation markers Ki-67 and survivin in separating malignant melanoma from benign nevi. Sixty-six melanocytic lesions (18 malignant melanomas, 8 Spitz nevi, 20 dysplastic nevi, and 20 compound nevi) were stained with antibodies to pHH3, Ki-67, and survivin. No pHH3 expression was detected in the dermis of compound and dysplastic nevi. Rare mitoses were observed in the superficial dermis in 3 of 8 Spitz nevi (37%). Staining for pHH3 was higher in malignant melanomas [average 25 per 10 high-power field (HPF), range 2-75 per 10 HPF] than in Spitz nevi (average 0.5 per 10 HPF, range 0-2 per 10 HPF) and was heterogeneously distributed in the malignant melanomas compared with a superficial dermal location in Spitz nevi. There was no cytoplasmic staining for survivin in any of the 66 melanocytic lesions and no nuclear staining in any of the benign ones. Survivin nuclear staining was present in 12 of 18 cases of malignant melanoma (67%) with an average index of 7% (range 0%-15%). In benign melanocytic lesions, the Ki-67 index was less than 5% (range 0%-4%) and staining was present close to the dermo-epidermal junction compared with an average index of 27% in melanomas (range 5%-50%) and a generally heterogeneous pattern of staining throughout the dermis. pHH3 and Ki-67 can be useful adjuncts to histopathology to separate malignant melanoma from benign nevi. pHH3 is especially useful to highlight mitoses and to rapidly assess the mitotic activity in melanocytic lesions.

The immunohistochemical profile of Spitz nevi and conventional (non-Spitzoid) melanomas: a baseline study

“…Thus, as earlier observed, Ki-67, a cell-cycle-associated nuclear antigen, nuclear survivin, a mitotic regulator by preserving microtubule stability, 38 and topoisomerase IIa, exclusively expressed in the proliferating compartments of normal tissues and tumors, 39 are significantly increased in melanoma vs nevus. 8,[40][41][42][43] Although melanomas show higher proliferation rates (37 vs 0% in Spitz nevi) when assessed with Ki-67, few cases of Spitz nevi show scattered positive cells at the top of the lesion, whereas melanoma has nuclear labeling throughout the lesion. 41,42 The structural membrane-scaffolding protein caveolin, with additional function in the transduction of signals from the plasma membrane, showed a loss of expression in vertical growth phase melanomas when compared with nevi.…”

Comparative diagnostic and prognostic performances of the hematoxylin-eosin and phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma

“…This protein is detected maximally during mitotic chromosome condensation in early prophase and negligibly at any other times (including apoptosis). 11,12 Phospho-histone H3 immunostaining has been shown to be a reliable and easy method for mitotic index evaluation in melanoma, with both diagnostic [13][14][15][16][17][18] and prognostic 17,[19][20][21] implications. Moreover, it has been also successfully applied in different neoplasms of the breast, [22][23][24][25][26] meninges, [27][28][29] brain, 30 lung, 31 soft tissues, [32][33][34] esophagus, 35 female genital tract, 36,37 prostate, 38 and urothelium, 39 as well as in cytology material from pancreatic endocrine tumors 40 and urothelial carcinoma.…”

Anti-phosphorylated histone H3 expression in Barrett's esophagus, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma

“…Mitotic counts have shown to be useful in differentiating between in situ and invasive carcinoma in cervical squamous carcinoma, 31 endocervical adenocarcinoma, 32,33 and melanoma. 34 To our knowledge, this is the first study showing the utility of mitotic figures in differentiating invasive carcinoma from highgrade dysplasia in the Barrett's esophagus.…”