Expression of CD40, CD44, bcl‐2 antigens and rate of cell proliferation on fine needle aspirates from metastatic melanoma

Abstract

The clinical behaviour of melanoma is often unpredictable using clinical and histological criteria. Tumour cell markers related to cell cycle regulation, apoptosis, cell-cell interactions and cell proliferation might improve the possibility of predicting the clinical course of melanoma. The aim of the present study was to refine prognostic criteria by an immunocytochemical investigation of CD44, CD40, bcl-2 antigens and cell proliferation in tumour cells aspirated from metastases of malignant melanoma. CD40 is a cell surface receptor shown to be expressed by lymphomas as well as carcinomas, and is thought to play a central role in the process of tumour progression. CD44 is a transmembrane glycoprotein, which is involved in growth signal transmission of importance in the binding of tumour cells to endothelium, cell migration and enhancement of cell motility, which makes it of interest to study in relation to the metastasizing capacity of tumours. The bcl-2 protein is active in the process of programmed cell death (apoptosis) as an antiapoptotic agent and its expression may reflect tumour progression. Mean/median percentages of tumour cell positivity were 8.5/3.0 for CD40, 76.1/86.3 for CD44 and 7.4/3.3 for bcl-2. A significant correlation was observed between expression of apoptosis-associated bcl-2 antigen and overall survival (r = 0.33). The CD44 positive cell fraction was higher in patients with short overall survival than those with long survival but this difference was not statistically significant. The expression of CD40 did not correlate with overall survival. The mean/median proliferation fraction assessed by MIB-1 monoclonal antibody was 25.8/23.9 and showed a significant correlation with survival after diagnosis of melanoma metastasis (r = 0.32). Lack of bcl-2 expression and a high proportion of tumour cells expressing Ki-67 antigen are predictors of poor prognosis that are independent of the traditionally accepted Breslow's thickness of the primary melanomas.

Camptothecin-induced death of amelanotic and melanotic melanoma cells in different phases of cell cycle

“…Over 1/3 of the examined melanotic and amelanotic melanoma were in S and G2/M phases which confirms the opinion that melanoma is a tumor with high proliferation rate [6,22]. But our observation that the amelantic form has more cells in S/G2/M phases than the melanotic one is of special importance because there are not such data in the melanoma literature although there is a common opinion that the amelanotic form is a more aggressive, rapidly growing melanoma form [16,23].…”

“…The results of other authors concerning the relationships between tumor growth and the ability of its cells to proliferate and undergo apoptosis are controversial; some authors showed that tumor growth depended mainly on cell proliferation [27], others indicated that both proliferation and apoptosis increased [28,29], that higher proliferation with decreased ability to undergo apoptosis supported tumor progression [29]. Observations of others that human melanoma cells have very low ability to undergo spontaneous apoptosis [30] and proliferating cells accounted for 20-40% of all cells [22] led them to the conclusion that the growth of human melanoma depends mainly on cell proliferative activity [31,32]. In contrast, our results may suggest that the expansive growth of the amelanotic melanoma line depends mainly on the decreased ability of cells in all cell cycle phases to undergo spontaneous apoptosis.…”

Immunohistochemical characteristics of melanoma

“…101,102,[104][105][106] CD40, a B cell marker that is also involved in tumor suppression, has increased expression in melanomas relative to nevi but has not been convincing as a prognostic marker. 107,108 van den Ord 109 studied CD26, an adenosine deaminase receptor, and found slightly increased staining in melanomas relative to benign nevi but no prognostic significance. There are conflicting reports of the expression of FAS and FASligand (tumor suppressor proteins of the tumor necrosis family) in melanomas and nevi and neither has been shown to be an independent prognostic factor.…”

Automated Quantitative Analysis of Tissue Microarrays Reveals an Association between High Bcl-2 Expression and Improved Outcome in Melanoma

“…Studies report a wide range of frequencies of Bcl-2 expression (60%-96%), with inconsistent associations between Bcl-2 expression and clinical outcome. Some studies report that up-regulation of Bcl-2 correlates with advanced stage and poor prognosis (11)(12)(13), whereas others report that down-regulation of Bcl-2 is associated with disease progression, advanced stage, and poor prognosis (14 -19). It is important to note that other studies have shown that Bcl-2 expression does not change during tumor progression, with equivalent expression levels in melanoma and normal melanocytes (20 -22).…”