Krishnakumar S, Lakshmi S A, Abhyankar D, Biswas J
Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 18 College Road, Chennai-600 006, Tamil Nadu, India.
Br J Ophthalmol. 2004 Jul;88(7):925-8. doi: 10.1136/bjo.2003.018457.
BACKGROUND/AIM: Transporter associated protein (TAP) is important for presenting peptides to major histocompatibility complex (MHC) class I molecules. Defects in TAP lead to decreased MHC class I expression. The immunoexpression of human leucocyte antigen (HLA) class I molecules and the TAP1 subunit were studied in primary uveal melanomas and correlated with the cell types and extrascleral extension.
The HLA class I antigen and TAP1 subunit were analysed by immunoperoxidase staining with monoclonal antibodies on 45 primary uveal melanoma archival specimens. The tumours were divided into two groups-group A: tumours with no extrascleral extension; group B tumours with extrascleral extension/liver metastasis. Immunoanalysis was done by a semiquantitative method.
HLA class I antigen and TAP1 were decreased in 35 of 35 tumours with no extrascleral extension and positive in six of 10 tumours with liver metastasis. Decreased immunoexpression of HLA class I antigen and TAP1 in uveal melanomas with no extrascleral extension was significant (p<0.001). HLA class I antigen and TAP1 were negative in spindle cell melanomas (p<0.001).
HLA class I antigen and TAP1 expression were decreased in uveal melanomas with no extrascleral extension and in spindle cell melanomas. Decreased expression of TAP1 may lead to decreased expression of HLA class I antigen in uveal melanomas. This preliminary observation deserves further investigation, which may shed more light on the immune escape mechanisms of this tumour and thus enable novel therapeutic strategies.
背景/目的:转运相关蛋白(TAP)对于将肽段呈递给主要组织相容性复合体(MHC)I类分子至关重要。TAP缺陷会导致MHC I类分子表达降低。本研究对原发性葡萄膜黑色素瘤中人类白细胞抗原(HLA)I类分子和TAP1亚基的免疫表达进行了研究,并将其与细胞类型和巩膜外扩展情况相关联。
采用单克隆抗体免疫过氧化物酶染色法,对45例原发性葡萄膜黑色素瘤存档标本进行HLA I类抗原和TAP1亚基分析。将肿瘤分为两组:A组为无巩膜外扩展的肿瘤;B组为有巩膜外扩展/肝转移的肿瘤。免疫分析采用半定量方法。
35例无巩膜外扩展的肿瘤中,HLA I类抗原和TAP1均降低,10例有肝转移的肿瘤中有6例呈阳性。无巩膜外扩展的葡萄膜黑色素瘤中,HLA I类抗原和TAP1免疫表达降低具有显著性(p<0.001)。梭形细胞黑色素瘤中HLA I类抗原和TAP1均为阴性(p<0.001)。
无巩膜外扩展的葡萄膜黑色素瘤和梭形细胞黑色素瘤中HLA I类抗原和TAP1表达降低。TAP1表达降低可能导致葡萄膜黑色素瘤中HLA I类抗原表达降低。这一初步观察结果值得进一步研究,这可能会更深入地揭示该肿瘤的免疫逃逸机制,从而制定新的治疗策略。