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男性乳腺癌肿瘤微环境,重点关注 TIL(肿瘤浸润淋巴细胞)和 PD-L1 表达

英文原题:Tumor Microenvironment in Male Breast Carcinoma with Emphasis on Tumor Infiltrating Lymphocytes and PD-L1 Expression.

查看英文原题

Tumor Microenvironment in Male Breast Carcinoma with Emphasis on Tumor Infiltrating Lymphocytes and PD-L1 Expression.

PubMed 2023/01/03(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

男性乳腺癌(MBC)较为罕见,通常表现为局部晚期疾病。在女性乳腺癌的所有分子亚型中,间质TIL(肿瘤浸润淋巴细胞)(sTILs)与新辅助化疗更好的反应及改善的预后相关,但其在MBC中的作用尚不明确。

我们研究了MBC中的sTILs以及程序性细胞死亡配体1(PD-L1)和pan-TRK的表达。我们回顾性研究了1988年至2015年间接受手术治疗的113例MBC病例。对肿瘤进行了组织学类型和分级、分期、内在亚型和sTILs的评估。

我们在组织芯片上进行了PD-L1(克隆SP142)和pan-TRK(克隆EPR17341)的免疫组化检测。pan-TRK阳性病例进一步通过下一代测序进行分析。中位年龄为69岁(范围60−77)。94.7%的病例为浸润性癌非特殊类型,其中53.1%为2级。雌激素受体在92%的肿瘤中为阳性,孕激素受体在85.8%中为阳性,雄激素受体在70.8%中为阳性;4.4%为人表皮生长因子受体2(HER2)阳性,55.8%为HER2低表达。40.7%的肿瘤为luminal A型,51.3%为luminal B型,4.4%为HER2富集型,3.5%为三阴性癌。96.4%的肿瘤中sTILs密度<50%,3.6%的肿瘤中>50%。7.1%的肿瘤中发现PD-L1免疫细胞评分>1%(均为luminal亚型)。8.8%存在弱的局灶性细胞质pan-TRK染色,但无NTRK融合。sTILs和PD-L1均无统计学显著结局。

我们的研究结果表明,一部分MBC患者具有以sTILs增加伴PD-L1表达为特征的免疫环境。这些患者可能潜在受益于免疫检查点抑制剂治疗。频繁的HER2低表达可能提供新的抗HER2治疗选择。

展开英文摘要原文

Male breast cancer (MBC) is rare and usually presents as a locally advanced disease. Stromal tumor-infiltrating lymphocytes (sTILs) are associated with a better response to neoadjuvant chemotherapy and improved prognosis in all molecular subtypes of female breast cancer, but their role in MBC is less clear.

We studied sTILs and the expression of programmed cell death ligand 1 (PD-L1) and pan-TRK in MBC.

We retrospectively studied 113 cases of MBC surgically treated between 1988 and 2015. The tumors were evaluated for histological type and grade, stage, intrinsic subtype and sTILs.

We performed immunohistochemistry for PD-L1 (clone SP142) and pan-TRK (clone EPR17341) on tissue microarrays. Pan-TRK positive cases were further analyzed by next-generation sequencing. The median age was 69 years (range 60−77). Invasive carcinoma of no special type was found in 94. 7% of cases, of which 53. 1% were grade 2. Estrogen receptor was positive in 92% of the tumors, progesterone receptor in 85. 8%, androgen receptor in 70. 8%; 4.

4% were human epidermal growth factor receptor 2 (HER2)-positive, and 55. 8% HER2-low. 40. 7% of tumors were luminal A and 51. 3% luminal B, 4. 4% HER2-enriched and 3. 5% triple negative carcinoma. sTILs density was <50% in 96. 4% of the tumors, >50% in 3. 6% of the tumors. PD-L1 immune cell score >1% was found in 7. 1% of the tumors (all of luminal subtype). A weak focal cytoplasmic pan-TRK staining was present in 8. 8% but without NTRK fusion. Neither sTILs nor PD-L1 had statistically significant outcomes.

Our findings suggest that a subset of MBC patients harbors an immunological environment characterized by increased sTILs with PD-L1 expression. These patients may potentially benefit from immune checkpoint inhibitor therapy. Frequent HER2-low may offer novel anti-HER2 treatment options.

论文信息

作者
Brcic I、Kluba AM、Godschachner TM、Suppan C、Regitnig P、Dandachi N、Lax SF、Balić M
第一作者单位
Diagnostic and Research Institute of Pathology, Comprehensive Cancer Centre, Medical University of Graz, 8010 Graz, Austria.Austria
通讯作者单位
Division of Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.Austria
期刊
International journal of molecular sciences2023 Jan 3
原文标识
PubMed 36614261 · DOI 10.3390/ijms24010818