Proliferating Giant Pigmented Nevus: A Report of an Unusual Tumor Occurring in Association with a Congenital Giant Pigmented Nevus

A 32-year-old Japanese woman with a giant pigmented congenital nevus of the torso presented with a massive pigmented tumor mass of the vulva which grew over an 8-year period. Histologically, the tumor was composed of benign appearing nevus-like cells with focal areas of extensive fibrous response. The tumor cells were positive for S-100 protein and with an antihuman melanoma antibody (MoAb 225, 28S) stain. Electron microscopy confirmed the nevomelanocytic nature of the tumor cells and demonstrated peculiar cytoplasmic crystalline tubular structures similar to those seen in cells infected with herpes virus type II. We propose the term “proliferating giant pigmented nevus” for this previous undescribed tumor. J Invest Dermatol 92:315S–317S, 198

Immunohistochemical Analysis of Antimelanoma Monoclonal Antibodies, with Special Reference to Fetal Tissue Distribution

An immunohistochemical study using 2 antihuman melanoma monoclonal antibodies designated as MoAb 225.28S and MoAb 653.40S was carried out on various human skin tumors, including malignant melanoma as well as on normal and fetal tissues by indirect immunofluorescence technique. Specific immunofluorescence was observed not only in malignant melanoma cells but also in cells of pigmented nevi, basal cell epithelioma, normal hair follicles, and some fetal tissues. Both monoclonal antibodies were revealed to be able to recognize the common antigenic determinant shared by several skin tumors, including malignant melanoma, and fetal tissues. Therefore, both monoclonal antibodies might recognize premature antigen of both melanocytic and keratinocytic cell lineage

Protein Kinase C α Associates with Phospholipase D1 and Enhances Basal Phospholipase D Activity in a Protein Phosphorylation-Independent Manner in Human Melanoma Cells

It is well known that phospholipase D plays a crucial part in the signal transduction of many types of cells, and is activated by protein kinase C α when cells are stimulated. To elucidate the role of phospholipase D in melanoma, the expression of phospholipase D1 and protein kinase C α in primary and metastatic lesions of acral lentiginous melanoma and superficial spreading melanoma was investigated using immunohistologic techniques. In addition, the mechanism of regulation of phospholipase D1 by protein kinase C α was examined in a human melanoma cell line HM3KO using an adenovirus-mediated gene transfer technique. Both phospholipase D1 and protein kinase C α were strongly expressed in primary and metastatic lesions of superficial spreading melanoma. Conversely, in acral lentiginous melanoma lesions, the expression of these two proteins increased dramatically with tumor progression; the expression of both phospholipase D1 and protein kinase C α was almost negative in the radial growth phase of primary acral lentiginous melanoma lesions, and increased synchronously in a progression-related manner in advanced acral lentiginous melanoma lesions, including vertical growth phase and metastatic lesions. Immunoprecipitation study showed that phospholipase D1 and protein kinase C α are associated physiologically in resting melanoma cells. Further immunoprecipitation study using HM3KO cells after adenovirus-mediated simultaneous overexpression of phospholipase D1 and protein kinase C α, or phospholipase D1 and the kinase-negative mutant of protein kinase C α revealed that both protein kinase C α and the kinase-negative mutant of protein kinase C α are associated with phospholipase D1 in melanoma cells in the absence of an external signal. Overexpression of protein kinase C α or the kinase-negative mutant of protein kinase C α in melanoma cells by the adenovirus vectors resulted in the enhancement of basal phospholipase D activity in a viral concentration-dependent manner. Furthermore, enhanced basal phospholipase D activity increased the in vitro invasive potential of HM3KO cells. These results suggest that upregulation of phospholipase D1 and protein kinase C α plays a part in the progression of acral lentiginous melanoma from the radial growth phase to the vertical growth phase. The present results also suggest that protein kinase C α associates with phospholipase D1 and enhances basal phospholipase D activity in a protein phosphorylation-independent manner in melanoma cells, which contributes to the cell's high invasive potential