Diagnostic significance of intratumoral CD8+tumor-infiltrating lymphocytes in medullary carcinoma
Diagnostic significance of intratumoral CD8+tumor-infiltrating lymphocytes in medullary carcinoma
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DOI：
10.1016/j.humpath.2017.10.020
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发表时间：
2017-12-01
期刊：
影响因子：
3.3
通讯作者：
Saito, Mitsue
中科院分区：
文献类型：
--
作者：
Igari, Fumie;Sato, Eiichi;Saito, Mitsue
乳腺浸润性导管癌具有明显的间质淋巴细胞浸润，经新辅助化疗后病理完全缓解率高，被归类为淋巴细胞占优势的乳腺癌(LPBC)。髓样癌(MC)是一种罕见的浸润性乳腺癌亚型，与LPBC一样伴有丰富的淋巴浆细胞浸润，独立于LPBC。尽管MC表现出明显的细胞和结构异型性，但它通常有良好的预后。有时很难区分MC和LPBC，因为根据目前的诊断标准，这两种亚型都有非特异性的形态特征。在此，我们采用多重荧光免疫组织化学方法对肿瘤浸润性淋巴细胞(TIL)进行了定量和同步分析，并考察了MC和LPBC的局灶性免疫反应差异。我们发现CD8+TIL在肿瘤内占优势，而CD4+TIL在MC中较少见。在非管腔型癌中，MC间质和瘤内CD8+TIL的数量显著高于LPBC。对CD4+TIL亚群的分层分析显示，即使在抑制环境中，CD8+TIL在非管腔型MC中也有很强的渗透，如此低的T辅助1/调节性T细胞比率。我们的结果表明，广泛的CD8+TIL浸润可能是鉴别MC和LPBC的一个有前景的生物标志物，特别是在非腔型癌中。瘤内CD8+TIL和非管腔固有亚型可作为诊断特征，从而为重复性诊断MC建立可靠的组织学标准。(C)2017 Elsevier Inc.保留所有权利。
Invasive ductal carcinomas of breast with marked stromal lymphocytic infiltration have come to be classified as lymphocyte-predominant breast cancer (LPBC) because it obtains high pathological complete response rates with neoadjuvant chemotherapy. Medullary carcinoma (MC), which is independent from LPBC, is a rare histological subtype of invasive breast carcinoma accompanied by abundant lympho-plasmacytic infiltration as LPBC. Although MC shows marked cellular and structural atypia, it usually has a favorable outcome. It is occasionally difficult to distinguish MC from LPBC because both subtypes have nonspecific morphological features according to the present diagnostic criteria. Herein, we adopted multiplexed fluorescent immunohistochemistry to perform quantitative and simultaneous analyses of tumor-infiltrating lymphocytes (TILs) considering their spatial distribution and examined focal immune reaction differences between MC and LPBC. We found that CD8+ TILs are predominant in the intratumoral region, whereas CD4+ TILs are less common in MC. In non luminal-type cancers, the numbers of stromal and intratumoral CD8+ TILs were significantly higher in MC than in LPBC. Stratified analyses by CD4+ TIL subsets showed robust infiltration of intratumoral CD8+ TILs in non luminal-type MC even in suppressive environments, such a low T helper 1-to-regulatory T cell ratio. Our results suggest that extensive intratumoral CD8+ TIL infiltration might well be a promising biomarker for distinguishing MC from LPBC, especially in non luminal-type cancers. Intratumoral CD8+ TILs and nonluminal intrinsic subtypes may serve as diagnostic characteristics allowing reliable histological criteria to be established for reproducibly diagnosing MC. (C) 2017 Elsevier Inc. All rights reserved.