Malignant melanoma protein

Proleukin is a recombinant form of IL-2. It is approved for the treatment of malignant melanoma and renal cell cancer. Ontak (denileukin diftitox) is a fusion protein for the treatment of persistent or recurrent T-cell lymphoma. Activated T cells express lL-2 receptors. Ontak has a fragment that binds to the IL-2 receptor while the other part presents a diphtheria toxin to kill the activated T cell. 

IL-2 promotes the growth of B cells for antibody production and induces the release of IFN-yand TNF (see below). It has been approved by the FDA for the treatment of different types of cancer, including metastatic melanoma and metastatic renal carcinoma. Examples of IL-2 for the treatment of malignant melanoma and a protein that targets IL-2 receptor in T-cell lymphoma are given in Exhibit 4.9. 

Panka DJ, Atkins MB, Mier JW. Targeting the mitogen-activated protein kinase pathway in the treatment of malignant melanoma. Clin. Cancer Res. 2006 12(7, Pt. 2) 2371s-2375s. 

Three interleukins (ILs) are in use for renal cell carcinoma and malignant melanoma (IL-2), cutaneous T-cell lymphoma (denileukin), and thrombocytopenia associated with cancer chemotherapy (IL-11). These interleukins are protein products that can cause substantial multiorgan toxicity, especially cardiovascular, and limit their full clinical usefulness, which characterizes most interleukins. Denileukin is a fusion protein of IL-2 and diphtheria toxin (Table 9). 

Hairy cell leukemia is the present indication for interferon alfa-2b. It is also useful in treadng malignant melanoma and renal cell carcinoma. Hyperseresitivity to this protein has not been ob.served. Patients develop a flu-like syndrome, CNS effects, and cardiovascular effects, including hypotension, arrhythmia, or tachycardia. 

Deichmann M, Polychronidis M, Wacker J et al (2001) The protein phosphatase 2A subunit Bgamma gene is identified to be differentially expressed in malignant melanomas by subtractive suppression hybridization. Melanoma Res 11 577-585... 

FIGURE 4.24 Clear cell sarcoma labels for S-100 protein in accord with the contention that it is a malignant melanoma of soft tissues. 

The immunohistochemical attributes of CCS do largely mirror those of malignant melanoma. They include reactivity for vimentin, S-100 protein (Fig. 

Gaynor R, Me R, Morton D, et al. SlOO protein a marker for human malignant melanomas Lancet. 1981 1 869-871. 

Heegaard S, Jensen OA, Prause JU. Immunohistochemical diagnosis of malignant melanoma of the conjunctiva and uvea comparison of the novel antibody against Melan-A with SlOO protein and HMB-45. Melanoma Res. 2000 10 350-354. 

Blessing K, Sanders DS, Grant JJ. Comparison of immunohistochemical staining of the novel antibody melan-A with SlOO protein and HMB-45 in malignant melanoma and melanoma variants. Histopathology. 1998 32 139-146. 

Fernando SS, Johnson S, Bate J. Immunohistochemical analysis of cutaneous malignant melanoma comparison of SlOO protein, HMB-45 monoclonal antibody, and NKI/C3 monoclonal antibody. Pathology. 1994 26 16-19. 

Orchard GE. Comparison of immunohistochemical labeling of melanocyte differentiation antibodies melan-A, tyrosinase, and HMB-45 with NKI/C3 and SlOO protein in the evaluation of benign nevi and malignant melanoma. Histochem J. 2000 32 475-481. 

Laskin WB, Knittel DR, Frame JN. SlOO protein and HMB-45-negative rhabdoid malignant melanoma a totally dedifferentiated malignant melanoma Am J Clin Pathol. 1995 103 772-773. 

Drier JK, Swanson PE, Cherwitz DL, Wick MR. SlOO protein immimoreactivity in poorly differentiated carcinomas. Immu-nohistochemical comparison with malignant melanoma. Arch Pathol Lab Med. 1987 111 447-452. 

BRAE is a serine/threonine protein kinase, which is a potent activator of the MAPK pathway. Mutations in this gene have been found in approximately two thirds of malignant melanomas and in a similar proportion of ovarian and colonic adenocarcinomas. The most common mutation results in a thymidine-to-adenine transversion at nucleotide position 1799 and a valine to glutamate substitution at residue 600 (V600E). An identical substitution has been identified in 40% to 70%... 

As known by most surgical pathologists, malignant melanomas may show significant variability in differentiation. Nearly all show immunostaining for S-100 protein and vimentin. Approximately 50% immuno-stain for human melanoma black-45 (HMB-45) antigen. Most stain for pan melanoma antibody. Rare melanomas immunostain for keratin, " which can cause diagnostic confusion. 

This nuclear transcription factor is involved in embryonic morphogenesis and is functionally related to c-kit and placental alkaline phosphatase (PLAP) expression. Nuclear staining is demonstrated in IGCNU and seminoma with a high degree of sensitivity. Positivity in nonseminomatous GCT is of lower sensitivity and, like podoplanin, activator protein-2G is also expressed in nontesticular neoplasms such as somatic malignant melanoma and mammary and ovarian carcinomas. ... 

Expression of cytokeratin, epithelial membrane antigen, CD99, and S-100 protein are potential diagnostic pitfalls in the distinction from metastatic or sarcomatoid carcinoma, EWS/PNET, synovial sarcoma, malignant melanoma, and other malignancies. 

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