Search

The reactivity in an avidin-biotin complex immunoperoxidase reaction with a large panel of anti-human melanoma associated antigen (MAA) and anti-HLA monoclonal antibodies of 24 primary and 11 metastatic acral lentiginous melanoma (ALM) lesions was compared to that of 12 primary and 12 metastatic nodular melanoma (NM) lesions. The expression of the membrane bound vitronectin receptor, Mr 110,000 MAA, Mr 97,000 MAA, and intercellular adhesion molecule-1 was significantly lower in both primary and metastatic ALM lesions than in their NM counterparts. Furthermore, primary ALM lesions displayed a significantly lower expression than primary NM lesions of the membrane bound high molecular weight melanoma associated antigen (HMW-MAA), Mr 110,000 MAA, Mr 100,000 MAA, 9-O-acetyl-GD3, GD2-GD3, and GD2, of the cytoplasmic monoclonal antibody 465.12 defined MAA and of transferrin receptor and of HLA-DQ and DP antigens; ALM metastases expressed a significantly lower level of carcinoembryonic antigen-MAA than NM metastases. These antigenic differences do not reflect an antigenic paucity of ALM cells, since ALM lesions express a higher level of T4-tyrosinase than NM lesions and a level of HLA Class I antigens similar to that of NM lesions. In view of the use of HMW-MAA, Mr 97,000 MAA, and GD3 in immunoscintigraphy and/or in immunotherapy, it is noteworthy that the three antigens are expressed in a similar high percentage of ALM metastases and of primary and metastatic NM lesions, while the HMW-MAA is expressed in a markedly lower percentage of primary ALM lesions than Mr 97,000 MAA and GD3. However, the degree of heterogeneity of HMW-MAA within a positive primary ALM lesion, as measured by the percentage of stained melanoma cells, is lower than that of Mr 97,000 MAA and GD3. The expression of the antigens investigated in ALM and NM lesions was not correlated with the presence of lymphocyte infiltrates, melanin content of melanoma cells, and epithelioid and spindle type of melanoma cells in the lesions. On the other hand, the survival of patients with ALM was inversely correlated with the expression of intercellular adhesion molecule 1 or HMW-MAA in their primary lesions. A potential role of HMW-MAA in the course of the disease is suggested by its significantly higher expression in metastatic than in primary ALM lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

The immunogenicity in patients with melanoma of three high molecular weight melanoma associated antigens (HMW.MAA) defined by murine monoclonal antibodies (MoAb) was investigated. For this end sera from patients with melanoma (stage I, IV) and normal individuals were tested by inhibition assay and sandwich assay using antiidiotypic MoAb to anti HMW.MAA MoAb. In inhibition assay, sera were tested for their ability to inhibit the binding of murine antiidiotypic MoAbs to biotin conjugated anti HMW.MAA MoAbs. Some of the sera from patients with melanoma significantly inhibited the binding of antiidiotypic MoAb to anti HMW.MAA MoAb in comparison with that from normal individuals. In sandwich assay, sera were tested for their ability to bind to precoated murine antiidiotypic MoAb and to biotin conjugated anti HMW.MAA MoAbs. Positive findings suggest the existence of anti HMW.MAA antibodies in sera were showed in several sera from the patients, which were less in frequency than that in inhibition assay. These results suggest that HMW.MAA could elicit the immune response in some melanoma patients and also suggest that the assay anti HMW.MAA MoAb in sera will help us to understand the prognosis of the patients and to evaluate the usefulness of treatment with antiidiotypic MoAb as vaccine therapy.

Seventeen primary and sixteen metastatic surgically removed melanoma lesions were stained indirect immunoperoxidase with anti-GD3, GD2, GD2 + GD3, and acetyl-GD3 monoclonal antibodies. In primary melanoma 94%, 59%, 53%, and 76% of the lesions tested were evidently stained by anti-GD3, GD2, GD2 + GD3, and acetyl-GD3 monoclonal antibodies, respectively. In metastatic lesions 94%, 63%, 31%, and 31% of the lesions were stained by monoclonal antibodies, respectively. Expression of GD2 + GD3 and acetyl-GD3 were evidently decreased from primary lesion to metastatic lesions. And the heterogeneity of positive cells in lesions were noteworthy. It is also interesting that expression of ganglioside in ALM were much decreased than that of ganglioside in NM.

Immunohistochemical localization of nerve growth factor (NGF) receptor in normal skin and melanocytic tumor was analysed using monoclonal antibody. In normal skin and fetal skin NGF receptor was good marker for cutaneous nerve sheath and schwann cells. In melanocytic lineage, the NGF receptor was not expressed in fetal, normal and dermal melanocyte and weakly positive in only small part of nevus cell nest. Positive staining was seen in primary and metastatic melanoma lesion and restricted to melanoma cell membrane. The distribution of the receptor suggests that the NGF-receptor may be involved in the control of proliferation and malignant transformation in melanocytic lineage.

Sixteen primary and ten metastatic melanoma lesions were stained in indirect immunoperoxidase with HLA-DR, DP and DQ monoclonal antibodies. In primary lesions, HLA-DR, DQ and DP antigens were much more expressed in nodular melanoma lesions than in acral lentiginous melanoma lesions. In metastatic lesions HLA-DR, DQ and DP antigens were expressed more than in primary lesions, but there were no significant differences between ALM and NM. In primary melanoma, 82%, 75%, and 75% of lesions tested were stained by anti HLA-DR, DP and DQ monoclonal antibodies, respectively. In metastatic melanoma, 90% of the lesions tested were stained by anti HLA-DR, DP and DQ monoclonal antibodies. HLA-class II antigens on melanoma cells were much more expressed in cases of high levels of invasion, high degrees of lymphocyte infiltration, and lower melanin content.

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.

Three cases of pigmented basal cell carcinoma were reported which needed to be differentiated from malignant melanoma based on their location and clinical features. Clinicopathologically, they were characterized by a large number of melanophages in the stroma, blockade melanocytes in the parenchyma, and phagocytosis of melanosomes in tumor cells as well as a large number of intraparenchymal melanophages. Two cases were characterized by the aggregation of melanophages in cystic spaces caused by stellate atrophy.