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醛脱氢酶(ALDH1A1)在肺部光谱病变中区分正常干细胞和癌症干细胞:一项免疫组织化学评估。

Aldehyde dehyderogenase (ALDH1A1) delineating the normal and cancer stem cells in spectral lung lesions: An immunohistochemical appraisal.

作者信息

Yassin Fatma El-Zahraa Salah El Deen

机构信息

Department of Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt.

出版信息

Pathol Res Pract. 2016 May;212(5):398-409. doi: 10.1016/j.prp.2016.02.011. Epub 2016 Feb 6.

DOI:10.1016/j.prp.2016.02.011
PMID:26907783
Abstract

BACKGROUND AND AIM

ALDH1A1 is one of the promising cancer stem cell markers, it has been found in different cancers, including lung cancer. We aimed to assess its immunohistochemical expression in spectral lung lesions (neoplastic versus non neoplastic) and to correlate its expression with certain pathological parameters (e.g. histopathological type and tumor grade).

MATERIALS AND METHODS

The study included 105 specimens of spectral lung lesions (20 adjacent normal tissues, 64 non small cell carcinoma (NSCLCs), 16 small cell carcinoma (SCLCs) and six inflammatory pseudotumors, in addition to nine metastatic tumors to lymph nodes. Both H&E and immunohistochemical stained sections were assessed and evaluated according to quick immunoreactivity score.

RESULTS

ALDH1A1 expression showed a broad dynamic range of immunoreactivity score (0-8) in different types of lung cancers with strong reactivity of normal stem cells. Significant statistical associations were found between ALDH1A1 expression and squamous cell carcinoma & SCLC (p=0.02 and 0.003, respectively), with very high mean percentage of positive cells in SCLC (58.50±10.62), followed by adenocarcinoma and squamous cell carcinoma (38.37±35.12 and 22.77±13.89, respectively). Adenocarcinomas were classified according to the IASLC/ATS/ERS classification and grouped by architectural grade into low, intermediate and high. Heterogeneity of ALDH1A1 immunoreactivity scores within adenocarcinoma can reflect histological patterns heterogeneity with a strong association to the grade. Strong diffuse expression was seen in inflammatory pseudotumors and impressive membranous expression was noticed in metastatic tumors. Important pitfalls of ALDH1A1 immunostaining were applied for accurate interpretations.

CONCLUSION

We ascertained the presence of strong association between ALDH1A1 expression and both histological subtype & tumor grade of NSCLCs. We report a fascinating finding; ALDH1A1 heterogeneity within adenocarcinoma can be mapped to its histological patterns. Furthermore, we elucidated its presence in SCLCs and inflammatory pseudotumors. Also a comparative image was drawn between its expressions in the primary lung tissue and in the metastatic lymph nodes.

摘要

背景与目的

醛脱氢酶1A1(ALDH1A1)是一种很有前景的癌症干细胞标志物,已在包括肺癌在内的多种癌症中被发现。我们旨在评估其在肺部不同病变(肿瘤性与非肿瘤性)中的免疫组化表达,并将其表达与某些病理参数(如组织病理学类型和肿瘤分级)相关联。

材料与方法

本研究纳入了105例肺部不同病变的标本(20例相邻正常组织、64例非小细胞肺癌(NSCLC)、16例小细胞肺癌(SCLC)、6例炎性假瘤,另外还有9例淋巴结转移瘤)。对苏木精-伊红(H&E)染色切片和免疫组化染色切片均根据快速免疫反应评分进行评估。

结果

ALDH1A1表达在不同类型肺癌中显示出广泛的免疫反应评分动态范围(0 - 8),正常干细胞呈强反应性。在ALDH1A1表达与鳞状细胞癌和SCLC之间发现了显著的统计学关联(分别为p = 0.02和0.003),SCLC中阳性细胞的平均百分比非常高(58.50±10.62),其次是腺癌和鳞状细胞癌(分别为38.37±35.12和22.77±13.89)。腺癌根据国际肺癌研究协会(IASLC)/美国胸科学会(ATS)/欧洲呼吸学会(ERS)分类进行分类,并按结构分级分为低、中、高等级。腺癌内ALDH1A1免疫反应评分的异质性可反映组织学模式的异质性,且与分级密切相关。在炎性假瘤中可见强弥漫性表达,在转移瘤中可见明显的膜性表达。应用了ALDH1A1免疫染色的重要注意事项以进行准确解读。

结论

我们确定了ALDH1A1表达与NSCLC的组织学亚型及肿瘤分级之间存在强关联。我们报告了一个有趣的发现;腺癌内ALDH1A1的异质性可映射到其组织学模式。此外,我们阐明了其在SCLC和炎性假瘤中的存在情况。还绘制了其在原发性肺组织和转移性淋巴结中表达的对比图像。

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