A p16-Ki-67-HMB45 immunohistochemistry scoring system as an ancillary diagnostic tool in the diagnosis of melanoma
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RESEARCH
Open Access
A p16-Ki-67-HMB45 immunohistochemistry scoring system as an ancillary diagnostic tool in the diagnosis of melanoma Arnaud Uguen1,2,3,4*, Matthieu Talagas2,3,4, Sebastian Costa2, Sandrine Duigou2, Stéphanie Bouvier2, Marc De Braekeleer1,3,5 and Pascale Marcorelles2,3,4
Abstract Background: Melanoma is a skin cancer which treatment requires early diagnosis and large surgical removal. The histopathological diagnosis of a melanocytic tumour is sometimes difficult between a benign nevus and a malignant melanoma. We built an immunomarker-based score to differentiate nevi from melanomas. Methods: Two independent sets of 308 (first set) and 62 (validation set) formalin-fixed and paraffin embedded tumour samples were studied using p16-Ki-67 and HMB45-MelanA dual-staining immunohistochemistry. Results: In the first set of tumours, high Ki-67 index, low to null p16 immunohistochemistry and absence of HMB45 immunohistochemistry gradient were more frequent in melanomas (156 primary tumours and 78 metastases) than in nevi (74 tumours). Nevertheless, none of these single parameters was able to differentiate all primary melanomas from all nevi. We built a scoring system based on the addition of semi-quantitative scorings of Ki-67 (0: 20 %) and p16 (0:>50 % stained cells; 1:11–50 %; 2:1–10 %; 3:0 %) and HMB45 staining (0: gradient present; 1: doubtful/inconclusive gradient; 2: gradient absent). A p16-Ki-67-HMB45 total score from 0 to 9 permitted to classify nevi (score 50 %
11–50 %
1–10 %
0%
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p16-Ki-67 score: 0–7 p16-Ki-67-HMB45 score: 0–9
HMB45
Gradient present
Gradient doubtful or inconclusive
Gradient absent
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Fig. 1 Illustration of immunostaining patterns from the first set of tumours. a Dermal nevus in a 39-year-old woman with metastatic melanoma (HES). b Second melanocytic tumour of the back in the same patient initially typed as a nevus (HES). c The tumour shown in (a) presents a strong diffuse red p16 labelling with a Ki-67 index of less than 1 % (see positive control as nuclear DAB staining of basal keratinocytes) (Immunohistochemistry slide). d The tumour of the back shown in (b) is p16 negative in this field (5 % of stained cells in the whole tumour) and Ki-67 index has been estimated to 8 % of nuclear DAB stained tumour cells; this tumour was finally considered as a nevoid melanoma (the tumour was not stained with HMB45 IHC leading to a p16-Ki-67-HMB45 score of respectively 1 + 3 + 1 = 5). e Absence of HMB45 gradient in a nodular melanoma: note the strong and diffuse DAB staining of the whole tumour (HMB45 score 2). f HMB45 DAB and MelanA Red double immunostaining of a Spitz nevus: HMB45 staining is limited to junctional component without staining of the dermal nests, here strongly red-stained with anti-MelanA antibody (HMB45 score 0)
Uguen et al. Diagnostic Pathology (2015) 10:195
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Fig. 2 Receiver Operating Characteristic (ROC) curves comparison of single and combined immunohistochemical analyses and p-values of the Areas Under the Curves (AUC) of the Receiver Oper
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