Hussein M R, Elsers D A H, Fadel S A, Omar A-E M
Department of Pathology, Assiut University Hospitals, Faculty of Medicine, Assiut University, Egypt.
J Clin Pathol. 2006 Mar;59(3):316-24. doi: 10.1136/jcp.2005.028860.
Although the presence of tumour infiltrating lymphocytes (TIL) is a constant feature in melanomas, their immunophenotypic characterisation is still incomplete. We hypothesise that the transition from normal skin to benign naevi (BN) to melanocytic dysplastic naevi (MDN) to radial growth phase cutaneous malignant melanoma (RGP-CMM) to vertical growth phase cutaneous malignant melanoma (VGP-CMM) is associated with alterations in TIL. This study attempted to test this hypothesis and to characterise TIL in the melanocytic skin lesions.
In total, 74 lesions (12 BN, 12 MDN, 13 RGP-CMM, 26 VGP-CMM, and 11 metastatic melanomas) were examined using immunoperoxidase staining methods and antibodies targeting leukocyte common antigen (LCA+), T (CD3+) and B (CD20+) lymphocytes, and resting cytotoxic T cells (TIA-1+).
Histologically, the transitions from normal skin to BN to MDN to RGP-CMM to VGP-CMM was associated with a gradual increase in the numbers of TIL (total, parenchymal, stromal, perivascular, and epidermal TIL, as well as TIL at the base of the lesions). The numbers of TIL were higher at the stroma than at the parenchyma. Similarly, immunostaining revealed that these transitions were associated with a gradual increase in the staining values (staining intensity, percentage of positive cells, and immunoreactivity score) for LCA+, CD20+, CD3+, and TIA-1+cells. The number of CD3+ cells was higher than that of CD20+ cells. All these differences between the normal skin and the lesional ones reached statistical significance (p<0.01). The majority of CD3+ cells were TIA-1+ T cells with cytotoxic potential. Compared with primary melanomas, there was a decrease in TIL in metastatic melanomas.
The gradual increase in TIL during melanoma tumorigenesis may reflect increased antigenicity of the tumour cells. Although both humoral and cell mediated immunity are involved in melanomagenesis, the latter seems to have the major role. The immune profile of MDN suggests their intermediacy between BN and CMM.
尽管肿瘤浸润淋巴细胞(TIL)的存在是黑色素瘤的一个常见特征,但其免疫表型特征仍不完整。我们推测从正常皮肤到良性痣(BN)、黑素细胞发育异常痣(MDN)、放射状生长期皮肤恶性黑色素瘤(RGP-CMM)再到垂直生长期皮肤恶性黑色素瘤(VGP-CMM)的转变与TIL的改变有关。本研究试图验证这一假设并对黑素细胞性皮肤病变中的TIL进行特征描述。
总共74个病变(12个BN、12个MDN、13个RGP-CMM、26个VGP-CMM和11个转移性黑色素瘤)采用免疫过氧化物酶染色方法以及针对白细胞共同抗原(LCA+)、T(CD3+)和B(CD20+)淋巴细胞以及静息细胞毒性T细胞(TIA-1+)的抗体进行检测。
组织学上,从正常皮肤到BN、MDN、RGP-CMM再到VGP-CMM的转变与TIL数量的逐渐增加相关(包括总的、实质内的、间质的、血管周围的和表皮的TIL,以及病变底部的TIL)。间质中的TIL数量高于实质内的。同样,免疫染色显示这些转变与LCA+、CD20+、CD3+和TIA-1+细胞的染色值(染色强度、阳性细胞百分比和免疫反应性评分)逐渐增加相关。CD3+细胞的数量高于CD20+细胞。正常皮肤与病变皮肤之间的所有这些差异均具有统计学意义(p<0.01)。大多数CD3+细胞是具有细胞毒性潜能的TIA-1+ T细胞。与原发性黑色素瘤相比,转移性黑色素瘤中的TIL减少。
黑色素瘤发生过程中TIL的逐渐增加可能反映了肿瘤细胞抗原性的增加。尽管体液免疫和细胞介导免疫都参与黑色素瘤的发生,但后者似乎起主要作用。MDN的免疫特征表明它们介于BN和CMM之间。