Immunohistochemical expression of BCL‐2 in melanomas and intradermal nevi

Abstract

The BCL-2 gene is the prototype of a newly described family of oncogenes involved in tumorigenesis by blocking apoptosis, or programmed cell death. Overexpression of BCL-2 protein was originally described in follicular B-cell lymphomas bearing the 14;18 translocation. BCL-2 overexpression has also been described in other lymphomas and more rarely in neoplasms outside the lymphoid tissue. The aim of this paper is to determine the immunohistochemical expression of BCL-2 in intradermal nevi and primary invasive and metastatic melanoma. Formalin-fixed and paraffin-embedded tissues from 4 cutaneous melanoma metastases, 10 primary invasive melanomas, and 10 intradermal melanocytic nevi were immunolabeled with monoclonal antibodies directed against BCL-2 protein (Dako, clone 124) and Ki-67 antigen (Amac, clone MIB-1), after antigen retrieval techniques. Morphologically normal epidermal melanocytes expressed BCL-2, as did nevi and melanomas in virtually all cells. However, whereas the labeling in normal melanocytes and nevus cells showed a uniformly strong reactivity, melanoma cells showed a variable but mainly weak reactivity. Ki-67 antigen expression was restricted to melanomas. The widespread expression of BCL-2 suggests that this oncoprotein cannot be involved in the malignant transformation of melanocytic cells. It seems likely that the decreased BCL-2 expression detected in melanomas may reflect one further step of tumor progression in melanocytic neoplasms.

Mcl-1, Bcl-XL and Stat3 expression are associated with progression of melanoma whereas Bcl-2, AP-2 and MITF levels decrease during progression of melanoma

“…Ramsay et al 26 reported immunohistochemical detection of Bcl-2 in 100% of melanocytes and benign nevi, but found less expression in primary and metastatic melanoma. Similar results were reported by Saenz-Santamaria et al, 27 Collins et al 28 and Cerroni et al 29 The role of the other antiapoptotic proteins, Bcl-XL and Mcl-1 in melanoma is largely unknown. In 1998, Tang et al 20 reported that Bcl-2 was downregulated in melanoma but Bcl-XL and Mcl-1 were upregulated.…”

“…The results of this study are consistent in part with several immunohistochemic and Western blot studies carried out by others 26,27,29,33 over the past decade and are contrary to the concept that Bcl-2 expression is associated with progression of melanoma. Instead, our results show that Bcl-2 expression was associated with a good prognosis, as reported by Divito et al 34 in studies on tissue microarrays.…”

Immunohistochemically Detectable Bcl-2 Expression in Metastatic Melanoma: Association with Survival and Treatment Response

“…Negative controls for the staining reactions were obtained by omitting the primary antibodies and substituting them with normal mouse serum. Staining of scattered epidermal basal cells of skin metastases, infiltrating lymphocytes, as well as eccrine sweat glands and dermal papillae of the hair follicles served as positive internal controls for successful immunohistochemistry for Bcl-2 [16, 17, 18, 19, 20]. …”

Alteration of Cytokine Genes and bcl-2 Expression following Immunotherapy with Intralesional IFN-γ in a Patient with Tumor-Stage Mycosis fungoides

“…The presence of bcl-2 protein has been observed in several benign and malignant tumors of the skin, including melanoma, basal cell carcinoma, Merkel cell carcinoma and T cell lymphoma [23, 24, 25, 26, 27, 28]. Our results showed that bcl-2 protein expression was downregulated after successful treatment not only by intralesional IFN-γ therapy but also by PUVA and radiation therapy, which suggests that the reduced expression of bcl-2 may not be due to a direct effect of IFN-γ: The reduced expression of bcl-2 may result from successful treatments of MF.…”