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肺癌的分子特征:在印度北阿坎德邦的一家三级医疗中心使用免疫组织化学分析对诊断、预测和预后标志物的研究。

Molecular characterization of lung carcinomas: A study on diagnostic, predictive, and prognostic markers using immunohistochemical analysis at a Tertiary Care Center in Uttarakhand, India.

作者信息

Rao Shalinee, Anthony Michael Leonard, Chowdhury Nilotpal, Kathrotia Rajesh, Mishra Mayank, Naithani Manisha, Sindhwani Girish, Singh Neha

机构信息

Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

Department of Physiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

出版信息

J Carcinog. 2021 Oct 7;20:17. doi: 10.4103/jcar.jcar_14_21. eCollection 2021.

Abstract

INTRODUCTION

Focused studies in different geographic regions would delineate the underlying biological differences and molecular alterations in non-small cell lung cancer (NSCLC) worldwide. Previous studies in literature have documented limited characterization by studying a minimal number of biological markers. This study was done to evaluate expression of multiple immunomarkers including diagnostic, prognostic, and predictive markers in NSCLC for its characterization.

MATERIALS AND METHODS

This was an observational study conducted on 60 consecutive cases of NSCLC. Immunomarkers comprising of p63, p40, TTF-1, napsin A, B-Raf, c-Met, phospho-AKT (P-AKT), PTEN, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR) and K-Ras, synaptophysin, chromogranin and pan-cytokeratin were evaluated on paraffin-embedded tissue sections of NSCLC.

RESULTS

Age of patients with NSCLC in our study ranged from 35 to 90 years, and 93.3% of them were chronic smokers. 93.3% of cases presented in late stages (Stages III and IV) and 78% of cases were squamous cell carcinoma (SCC). EGFR positivity was noted in 83.3% of cases. ALK was positive in one case while C-Met and PTEN immunopositivity was noted in only two cases. Ten cases showed positivity for K-Ras and 90% of these were SCC. Ten cases were positive for B-Raf and 80% of these were SCC. 30% of cases showed immunopositivity for P-AKT. None of the molecular markers was found to have statistically significant correlation with clinicopathological parameters.

CONCLUSION

SCC is the predominant histological subtype of NSCLC in the region of Uttarakhand, India, with a high proportion of cases harboring EGFR mutation. Variable expression of K-Ras, P-AKT, ALK 1, and PTEN in NSCLC signifies that molecular profile of every case is individualistic and independent. We attribute this to ethnicity, influence of implicated substance or metabolite in tobacco, and variable mutations incurred in tumor cells over a period of time.

摘要

引言

针对不同地理区域的重点研究将阐明全球非小细胞肺癌(NSCLC)潜在的生物学差异和分子改变。既往文献研究通过检测少量生物标志物,其特征描述有限。本研究旨在评估多种免疫标志物(包括诊断、预后和预测标志物)在NSCLC中的表达,以对其进行特征描述。

材料与方法

这是一项针对60例连续NSCLC病例的观察性研究。在NSCLC石蜡包埋组织切片上评估免疫标志物,包括p63、p40、甲状腺转录因子-1(TTF-1)、 napsin A、B-Raf、c-Met、磷酸化AKT(P-AKT)、PTEN、间变性淋巴瘤激酶(ALK)、表皮生长因子受体(EGFR)和K-Ras、突触素、嗜铬粒蛋白和泛细胞角蛋白。

结果

本研究中NSCLC患者年龄在35至90岁之间,其中93.3%为长期吸烟者。93.3%的病例为晚期(Ⅲ期和Ⅳ期),78%的病例为鳞状细胞癌(SCC)。83.3%的病例EGFR呈阳性。ALK在1例中呈阳性,而C-Met和PTEN免疫阳性仅在2例中被发现。10例K-Ras呈阳性,其中90%为SCC。10例B-Raf呈阳性,其中80%为SCC。30%的病例P-AKT呈免疫阳性。未发现任何分子标志物与临床病理参数具有统计学显著相关性。

结论

在印度北阿坎德邦地区,SCC是NSCLC的主要组织学亚型,其中很大比例的病例存在EGFR突变。NSCLC中K-Ras、P-AKT、ALK 1和PTEN的表达各异,这表明每个病例的分子特征是个体化且独立的。我们将此归因于种族、烟草中相关物质或代谢产物的影响以及肿瘤细胞在一段时间内发生的可变突变。

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