Erythrophagocytic tumour cells in melanoma and squamous cell carcinoma of the skin

 

Aims:

Erythrophagocytosis is a characteristic feature of tumour cells in malignant histiocytosis, some leukaemias, lymphomas, and also reactive histiocytes in the haemophagocytic syndrome associated with a variety of infections and neoplasms. It has also been found exceptionally in metastatic malignant epithelial cells in bone marrow and lymph nodes. We present two cases, a cutaneous malignant melanoma and an acantholytic squamous cell carcinoma, in which erythrophagocytosis by tumour cells was demonstrable by both light and electron microscopy.  

Methods and results:

The melanocytic and squamous nature of these cells was supported by the immunohistochemical detection of HMB45, S100, and NKI-C3 in the former, and cytokeratin and EMA in the latter, and at ultrastructural level by the presence of melanosomes and tonofilaments, respectively.  

Conclusions:

This is, to our knowledge, the first documented report of erythrophagocytic tumour cells in human melanomas and primary carcinomas. Biological considerations apart, this unusual feature can prove to be of value to avoid a misdiagnosis of a variety of haematopoietic malignancies.     

The role of Bcl-2 family members in the progression of cutaneous melanoma

The overwhelming problem of cutaneous melanoma is chemoresistance. Subversion of the biochemical changes that lead to chemoresistance intersects the apoptosis pathways. The mitochondrion has been a focal point of this intersection for the development of therapeutic strategies aimed at reducing the progression of melanoma. The Bcl-2 family of apoptotic regulators is arguably the most pivotal component to this mitochondrial response. The shear number of studies conducted on the relationship between melanoma and Bcl-2 members prompted us to evaluate the literature available and discern some rational utility of the data. We have found that there are striking inconsistencies for the expression of Bcl-2 family proteins with melanoma progression, particularly for Bcl-2. Roughly one-third of the data suggests an increase in Bcl-2 expression with advancing melanoma, while another third suggests a decrease. Furthermore, the remaining third found on the whole, a detectable level of Bcl-2 in all tissues of melanocytic origin. These discrepancies are difficult to rectify in light of the apparent success of recent clinical trials utilizing Bcl-2 antisense strategies. The general consensus in the literature is that pro-apoptotic Bax is decreased with melanoma progression while anti-apoptotic Bcl-x_L and Mcl-1 appear to increase with progression. We suggest that the biochemical techniques being used for analysis present too great of a heterogeneity, which could be mitigated with more standard procedures and reagents. Finally the utility of ‘multi-specific’ antisense tactics could be a more effective way of targeting advanced melanoma disease. This revised version was published online in July 2006 with corrections to the Cover Date.     

血管生成因子在咽喉部恶性黑色素瘤的表达及与血管生成的关系

目的　研究血管内皮生长因子 (VEGF)、碱性成纤维细胞生长因子 (b FGF)、转化生长因子β1 (TGF-β1 )及其受体和肿瘤源性粘附因子 (TAF)在咽喉部恶性黑色素瘤中的表达特点 ,以及它们与肿瘤内微血管密度(MVD)和病人预后的关系。　方法　应用免疫组织化学和形态计量方法检测 2 8例咽喉部恶性黑色素瘤 MVD、VEGF、b FGF、TGF- β1 及其受体和 TAF的表达 ,并应用多因素 Cox比例风险模型检测上述因素和病人预后的关系。　结果　 2 8例咽喉部恶性黑色素瘤中 ,VEGF阳性 19例 (6 7.9% ) ,b FGF阳性 2 1例 (75 .5 % ) ,TGF- β1 阳性 16例 (5 7.1% ) ,TAF阳性 18例 (6 4.3% )。血管生成因子与其受体表达具有一致性 ,并与 MVD值显著相关。Cox模型分析显示 MVD和 VEGF是影响咽喉部恶性黑色素瘤的重要因素 (P<0 .0 5 )。　结论　 VEGF、b FGF、TGF- β1 和TAF是咽喉部恶性黑色素瘤中血管生成的重要因子 ,并通过促进血管生成影响病人的预后。其中 MVD和 VEGF是评估咽喉部恶性黑色素瘤病人预后的重要指标。     

The burden of cutaneous disease in solid organ transplant recipients of color

Organ transplant recipients (OTRs) are at increased risk of cutaneous malignancy. Skin disorders in OTRs of color (OTRoC) have rarely been systematically assessed. We aimed to ascertain the burden of skin disease encountered in OTRoC by prospectively collecting data from OTRs attending 2 posttransplant skin surveillance clinics: 1 in London, UK and 1 in Philadelphia, USA. Retrospective review of all dermatological diagnoses was performed. Data from 1766 OTRs were analyzed: 1024 (58%) white, 376 (21%) black, 261 (15%) Asian, 57 (3%) Middle Eastern/Mediterranean (ME/M), and 48 (2.7%) Hispanic; and 1128 (64%) male. Viral infections affected 45.1% of OTRs, and were more common in white and ME/M patients (P < .001). Fungal infections affected 28.1% and were more common in ME/M patients (P < .001). Inflammatory skin disease affected 24.5%, and was most common in black patients (P < .001). In addition, 26.4% of patients developed skin cancer. There was an increased risk of skin cancer in white vs nonwhite OTRs (HR 4.4, 95% CI 3.5-5.7, P < .001): keratinocyte cancers were more common in white OTRs (P < .001) and Kaposi sarcoma was more common in black OTRs (P < .001). These data support the need for programs that promote targeted dermatology surveillance for all OTRs, regardless of race/ethnicity or country of origin.     

Intrathecal IgM response in disseminated cerebrospinal metastasis from malignant melanoma

Summary Neurological complications are a major cause of morbidity and mortality in patients with disseminated malignant melanoma. We have studied and correlated clinical and cerebrospinal fluid (CSF) findings in 20 patients with central nervous system metastases from malignant melanoma including 8 patients with metastatic meningeal melanomatosis (MMM) and 12 patients with solid cerebral metastases (SCM). The putative CSF tumor markers, fibronectin and ₂-microglobulin, were elevated significantly in MMM but not in SCM patients. A prominent increase in the IgM index, which reflects intrathecal B-cell stimulation, and a rise of IgG index, interleukin-6, and tumor necrosis factor- in MMM patients provide preliminary evidence for a local intrathecal immune response triggered by melanoma cell invasion of the subarachnoid space.     

原发性女性生殖器恶性黑色素瘤16例分析

目的：探讨原发性女性生殖器恶性黑色素瘤的临床病理特点及合理的治疗方法。方法：对16例原发性女性生殖器恶性黑色素瘤的临床资料进行回顾性分析。结果：发生于外阴9例,阴道5例,子宫颈2例。全部病例均行手术加化疗综合治疗,行区域淋巴结清扫11例,4例有转移,转移率36.3％。存活＜2年8例,≥2年8例,其中≥5年仅2例。结论：原发性女性生殖器恶性黑色素瘤预后差,行根治手术辅化疗和免疫治疗,可望提高生存期。     

金属蛋白酶类及层粘连蛋白受体与人黑色素瘤细胞侵袭转移的关系

目的揭示金属蛋白酶类(MMPs)及层粘连蛋白受体(LN-R)与人黑色素瘤细胞侵袭转移的关系,并探讨MMPs及IN-R用以判断肿瘤细胞侵袭转移的可能性。方法通过流式细胞术(FCM)定量研究和蛋白酶活性分析(Zymography),对具有不同潜在转移能力的人黑色素瘤细胞系(WM35,WM134b,WM983a,WM451)进行MMPs及瘤细胞表面67000LN-R的荧光阳性率和全部细胞的平均荧光强度测定。结果早期WM35不产生MMPs;WM1341b仅产生MMP2,不产生MMP9;进展期WM983a和远处转移瘤株WM451既产生MMP2又产生MMP9。瘤细胞表面67000LN-R的荧光阳性率和全部细胞的平均荧光强度大小顺序为WM451>WM983a>WM1341b>WM35。结论MMPS和LN-R与人黑色素瘤细胞侵袭转移能力的获得之间关系密切,并可作为较特异的肿瘤侵袭转移标记物应用于肿瘤研究与治疗中。     

Immunogenicity and tumor-inhibiting effects of HSP-antigen peptide complex in melanoma B16 cells in mice

目的 :黑色素瘤 B1 6细胞热休克蛋白 -抗原肽复合物 (HACs)及其粗提物 (HAC- CEs)的制备 ,以及它们的免疫原性和抑瘤效应的研究。方法 :应用 Sephacryl S- 2 0 0凝胶过滤制备HAC- CEs,应用亲和层析纯化 HACs,并测其免疫功能和抑瘤效应。结果 :应用凝胶过滤制备的HAC- CE3、HAC- CE4、HAC- CE5和应用亲和层析纯化的 HAC60 ,HAC75和 HAC97均不同程度地降低肿瘤发生率、延迟肿瘤发生时间和减少移植黑色素瘤 C57BL/6J小鼠死亡率 ;同时 ,伴有小鼠脾细胞 IFN-γ和 IL- 2分泌活性及 CTL杀伤率的增加。结论 :分子量为 60 0 0 0～ 970 0 0的 HACs具有免疫原性和抑瘤效应 ,本研究为制备肿瘤疫苗提供重要的实验依据。     

Molecular approach to the nucleo-melanosomal interaction in human melanoma cells

This paper presents evidence that L-tyrosine oxidation products and 5,6-dihydroxyindole, an intermediate of melanin synthesis bind to and modify DNA structure, as tested by extracting cell DNA, using topoisomerase I and denaturation assays. When supercoiled plasmid pCU18 or pBR322 DNAs are treated with 5,6-dihydroxyindole the supercoiled species disappear and are converted to species less mobile in a gel retardation test with respect to relaxed DNA. 5,6-Dihydroxyindole causes an easier acid denaturation of the double helix. The results, that are dose dependent,would point to both intercalation and cross-linking of DNA by 5,6-dihydroxyindole and its oxidation product(s). ³H-L-tyrosine deriving radioactivity, bound to nuclear DNA, is higher at low pH, (5.6) if compared to pH 6.8. The highest radioactivity bound to cell DNA is found during the transition from the amelanotic to the melanotic phenotype in human melanoma cell lines. As a control, the binding of ³H-L-tyrosine radioactivity to human prostate fibroblast DNA was investigated.