Nuclear to non-nuclear Pmel17/gp100 expression (HMB45 staining) as a discriminator between benign and malignant melanocytic lesions

Rothberg, Bonnie E. Gould; Moeder, Christopher B.; Kluger, Harriet M.; Halaban, Ruth; Elder, David E.; Murphy, Gëorge F.; Lazar, Alexander J.; Prieto, Víctor G.; Duncan, Lynn Mc Divitt; Rimm, David L.

doi:10.1038/modpathol.2008.100

Cited by 34 publications

(29 citation statements)

References 26 publications

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“…They also performed a multi-marker diagnostic assay using 5 markers (ARPC2, FN1, RGS1, SPP1 and WNT2), which are over-expressed in melanoma cells. Gould Rothberg et al proposed that the ratio of nuclear to non-nuclear HMB45 immunofluorescence staining may be useful in the diagnosis of melanocytic lesions 29. Recent data has shown also that PAX3 is commonly expressed in primary melanoma samples (21/58), but significantly less frequently in benign pigmented lesions (9/75) 30.…”

Section: Discussionmentioning

confidence: 99%

The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

et al. 2011

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C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign and malignant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was performed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intra-dermal nevi, 3 junctional nevi, 15 cases of primary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were positive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient’s age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other variables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was negative. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplasmatic and membranous positivity for c-kit, in contrast with the absence of any immunoreactivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immunohistochemical marker for distinguishing melanoma from melanocytic nevi, if we consider c-Kit expression in intraepidermal proliferating cells. The c-Kit expression in proliferating melanocytes in the dermis could help in the differential diagnosis between a superficial spreading melanoma (with dermis invasion) and a compound nevus or an intradermal nevus. Finally, c-Kit could be a good diagnostic tool for distinguishing benign compound nevi from malignant melanocytic lesions with dermis invasion and to differentiate metastatic melanoma from primary melanoma.

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Section: Discussionmentioning

confidence: 99%

The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

et al. 2011

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“…A spectrum of melanocytic lesions was assessed. Among the cases studied were benign nevi, 13 atypical nevi of special sites, 10 recurrent nevi, 10 capsular nevi, 4 and malignant melanoma (superficial spreading and lentigo maligna, 14 acral lentiginous, 3 and nodular subtypes 7 ), as well as metastatic melanoma. 7 …”

Section: Methodsmentioning

confidence: 99%

“…Neither stain is specific nor especially sensitive, and HMB45 is positive in junctional nevomelanocytes and the superficial aspects of the dermal component, with a progressive decrease in expression toward the dermal base of a benign nevus. 2–4 Expression at varying levels throughout the dermal component can be observed in the setting of melanomas other than desmoplastic melanoma, in which this marker is usually negative. Nevertheless, there are benign lesions that express HMB45 in a pandermal fashion, including inverted type A nevus, deep penetrating nevus, blue nevus, and cellular blue nevus.…”

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confidence: 99%

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Soluble Adenylyl Cyclase Antibody Profile as a Diagnostic Adjunct in the Assessment of Pigmented Lesions

Magro

Crowson²,

Desman³

et al. 2012

Arch Dermatol

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“…(27) Briefly, paraffin blocks of human normal skin tissue obtained from freshly excised surgical specimens were cut into 5 mm sections and slides were deparaffinized using two xylene exchanges, followed by rehydration in an ethanol gradient. After antigen retrieval and non-specific binding blocking, slides were incubated with primary antibodies against PMEL (SPM142) for 1.5 h at 37°C, followed by washing three times.…”

Section: Immunohistochemistrymentioning

confidence: 99%

A Monoclonal Antibody Against PMEL

Shi

Xu²,

Chen³

et al. 2014

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

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PMEL, also known as Pmel17 or gp100, is a melanocyte-specific glycoprotein that is essential for the formation of stage II melanosomes. As it has a highly restricted expression pattern in normal tissues and a transient presence on the cell surface, PMEL is believed to be a potential target for antibody drug conjugate therapy in some pigmentary diseases. The production of a high specificity and high affinity monoclonal antibody against human PMEL was helpful for the antibody drug conjugate therapy study. In the present study, monoclonal antibodies (MAbs) against PMEL were obtained by immunizing BALB/c mice with the recombinant PMEL-GST fusion protein. Three mAbs (A3F, G11B, and J7E) with a titer of 1:6000, 1:10,000, and 1:3000, respectively, were obtained. Immunoglobulin subclass assay revealed that A3F was IgG2b, G11B was IgG1, and J7E was IgG2a. Specificity analysis by Western blotting demonstrated that A3F and J7E cross-reacted with GPNMB or LAMP; however, G11B reacted with PMEL only. Immunohistochemistry experiments showed that G11B could bind human PMEL antigen in normal skin. Flow cytometry assay demonstrated that G11B could bind to the surface of PMEL positive melanoma cells but not PMEL negative cells. Taken together, these results show that this G11B provides a useful tool for the antibody drug conjugate therapy study in some pigmentary diseases.

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Nuclear to non-nuclear Pmel17/gp100 expression (HMB45 staining) as a discriminator between benign and malignant melanocytic lesions

Cited by 34 publications

References 26 publications

The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

Soluble Adenylyl Cyclase Antibody Profile as a Diagnostic Adjunct in the Assessment of Pigmented Lesions

A Monoclonal Antibody Against PMEL

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