Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Pathology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
Mod Pathol. 2021 Jan;34(1):141-160. doi: 10.1038/s41379-020-0633-x. Epub 2020 Jul 24.
Anorectal malignant melanoma (ARMM) is a rare disease with poor prognosis. Determining ARMM prognosis precisely is difficult due to the lack of proper assessment techniques. Immunotherapy has proven effective against cutaneous malignant melanoma and may show efficacy in ARMM. Herein, we assessed the immune profile of ARMM to identify possible prognostic biomarkers. Twenty-two ARMM formalin-fixed and paraffin-embedded samples were evaluated using an nCounter PanCancer Immune Profiling Panel. Validation was performed through immunohistochemical staining for CD3, CD8, Foxp3, CD68, CD163, and PD-L1. RNA analysis revealed significantly decreased scores for pathways involved in cell regulation and function, as well as chemokines, in recurrent patients compared to nonrecurrent patients. In cell-type profiling, the recurrent cases displayed significantly low tumor infiltrating lymphocyte (TIL) scores. Recurrence/death prediction models were defined using logistic regression and showed significantly lower scores in recurrent and deceased patients (all, P < 0.001) compared to those in nonrecurrent and surviving patients. The high total TIL and tumor-associated macrophage (TAM) groups had significantly better overall survival outcomes compared to the low total TIL and TAM groups (P = 0.007 and P = 0.035, respectively). In addition, the presence of CD3 + TILs in the invasion front was an independent favorable prognostic indicator (P = 0.003, hazard ratio = 0.21, 95% confidential interval, 0.01-0.41). Patients with inflamed or brisk-infiltration type tumors also had a significantly better overall survival than that of patients with immune-desert/excluded and absent/non-brisk type tumors (P = 0.03 and P = 0.0023, respectively). In conclusion, TILs have a strong prognostic value in ARMM, and the quantification of TILs and an analysis of the TIL phenotype and infiltration pattern during pathological diagnosis are essential to guide treatment strategies and accurate prognosis in ARMM.
肛门直肠恶性黑色素瘤（ARMM）是一种预后较差的罕见疾病。由于缺乏适当的评估技术，准确确定 ARMM 的预后具有挑战性。免疫疗法已被证明对皮肤恶性黑色素瘤有效，并且在 ARMM 中可能显示出疗效。在此，我们评估了 ARMM 的免疫谱，以确定可能的预后生物标志物。使用 nCounter PanCancer 免疫分析面板评估了 22 例 ARMM 福尔马林固定石蜡包埋样本。通过 CD3、CD8、Foxp3、CD68、CD163 和 PD-L1 的免疫组织化学染色进行验证。RNA 分析显示，与非复发性患者相比，复发性患者涉及细胞调节和功能以及趋化因子的途径评分显著降低。在细胞类型分析中，复发性病例的肿瘤浸润淋巴细胞（TIL）评分显著降低。使用逻辑回归定义了复发/死亡预测模型，结果显示，与非复发性和存活患者相比，复发和死亡患者的评分显著降低（均 P<0.001）。高总 TIL 和肿瘤相关巨噬细胞（TAM）组的总生存率明显优于低总 TIL 和 TAM 组（P=0.007 和 P=0.035）。此外，侵袭前沿存在 CD3+TIL 是独立的有利预后指标（P=0.003，危险比=0.21，95%置信区间，0.01-0.41）。炎症或浸润型肿瘤患者的总生存率明显优于免疫荒漠/排除型和无/非浸润型肿瘤患者（P=0.03 和 P=0.0023）。总之，TIL 在 ARMM 中具有很强的预后价值，在病理诊断中定量分析 TIL 并分析 TIL 表型和浸润模式对于指导治疗策略和准确预测 ARMM 的预后至关重要。
