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PDL1 表达在促结缔组织增生性黑色素瘤中与肿瘤侵袭性和进展相关。

PDL1 expression in desmoplastic melanoma is associated with tumor aggressiveness and progression.

机构信息

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Department of Pathology, Hospital Universitari Germans Trias i Pujol, Univeristat Autònoma de Barcelona, Badalona, Barcelona, Spain.

出版信息

J Am Acad Dermatol. 2017 Sep;77(3):534-542. doi: 10.1016/j.jaad.2017.05.007. Epub 2017 Jul 18.

Abstract

BACKGROUND

The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear.

METHODS

We correlated PDL1, p53, and Ki-67 expression with CD8 and FoxP3 immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas.

RESULTS

Tumoral PDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis. According to linear regression analysis, tumoral PDL1 expression correlated with thickness (P = .0041); p53 expression (P = .019); Ki-67 proliferation index (P = .0018); and tumoral CD8 (P = .0084), stromal CD8 (P < .0001), and FoxP3 (P < .0001) T-cell counts. According to univariate analyses, PDL1 expression of 25% or higher correlated with shorter progression-free survival (P < .0001) and melanoma-specific survival (P = .034). According to multivariate analyses, PDL1 expression of 25% or more (P = .026) and mixed histology (P = .039) independently predicted shorter progression-free survival, and presence of lymphovascular invasion predicted shorter overall survival (P = .018).

LIMITATIONS

Small study size.

CONCLUSION

Tumoral and stromal CD8 and FoxP3 lymphocyte counts correlated with tumoral PDL1 expression, which is supportive of an adaptive immune response. PDL1 expression in desmoplastic melanoma was associated with tumor aggressiveness and progression. Although PDL1 expression is typically low in melanoma, its frequency and level of expression in desmoplastic melanoma may identify a subset of melanomas that are likely to respond to immunotherapy.

摘要

背景

程序性死亡配体 1(PDL1)、CD8 和叉头框 P3(FoxP3)表达在促结缔组织增生性黑色素瘤中的预后作用尚不清楚。

方法

我们将 PDL1、p53 和 Ki-67 的表达与 CD8 和 FoxP3 免疫浸润与一系列 66 例促结缔组织增生性黑色素瘤的临床病理变量和患者结局相关联。

结果

肿瘤 PDL1 表达(≥25%)在 21%的患者(66 例中的 14 例)中可见,与混合组织学、肿瘤厚度、有丝分裂、复发和转移显著相关。根据线性回归分析,肿瘤 PDL1 表达与厚度(P=0.0041);p53 表达(P=0.019);Ki-67 增殖指数(P=0.0018);肿瘤 CD8(P=0.0084)、基质 CD8(P<0.0001)和 FoxP3(P<0.0001)T 细胞计数相关。根据单因素分析,PDL1 表达≥25%与无进展生存期(P<0.0001)和黑色素瘤特异性生存期(P=0.034)较短相关。根据多因素分析,PDL1 表达≥25%(P=0.026)和混合组织学(P=0.039)独立预测无进展生存期较短,存在淋巴管血管侵犯预测总生存期较短(P=0.018)。

局限性

研究规模小。

结论

肿瘤和基质 CD8 和 FoxP3 淋巴细胞计数与肿瘤 PDL1 表达相关,这支持适应性免疫反应。促结缔组织增生性黑色素瘤中的 PDL1 表达与肿瘤侵袭性和进展相关。尽管 PDL1 表达在黑色素瘤中通常较低,但在促结缔组织增生性黑色素瘤中的频率和表达水平可能确定了一组可能对免疫治疗有反应的黑色素瘤。

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