Differential immunohistochemical expression of hTERT in lung cancer patients with and without idiopathic pulmonary fibrosis

IF 10.4 2区 医学 Q1 RESPIRATORY SYSTEM Pulmonology Pub Date : 2024-05-01 DOI:10.1016/j.pulmoe.2021.12.001
G. Gomatou , C. Masaoutis , I. Vamvakaris , E. Kotteas , E. Bouros , V. Tzilas , D. Bouros
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Abstract

Background

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase enzyme, which adds nucleotides to telomeres and counteracts their length shortening. The development of a telomere maintenance mechanism represents a hallmark of cancer. On the other hand, idiopathic pulmonary fibrosis (IPF) is associated with mutations in telomerase genes and shorter telomeres. IPF is frequently complicated with lung cancer.

Aim

To investigate the expression of hTERT in lung cancer with co-existing IPF and to compare with lung cancer without fibrosis.

Methods

Diagnostic lung cancerous biopsies were retrieved from 18 patients with lung cancer and concomitant IPF, as well as 18 age and gender matched controls with lung cancer without pulmonary fibrosis. The expression of hTERT was studied with immunohistochemistry. ImajeJ software was used to quantitate subcellular stain intensity. Immunohistochemical investigation of two senescence-associated markers, p16 and p21, was also performed in all 36 cases.

Results

Both groups highly expressed hTERT, without significant difference (100% vs 95%, p = 0.521). Evaluation of p16 and p21 immunostaining revealed negative to minimal immunoreactivity in both groups. hTERT localization exhibited higher median nuclear intensity in the group of lung cancer with IPF (0.62 vs 0.45, p = 0.016), while cytoplasmic intensity did not differ significantly (0.17 vs 0.15, p = 0.463). Higher median nuclear intensity was also correlated with small cell lung cancer subtype in the whole study sample (0.69 vs 0.45, p = 0.09).

Conclusion

hTERT is highly expressed in lung cancer with concomitant IPF, but with differential localization compared to lung cancer without IPF, implying differences in pathogenicity and requiring further investigation.

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有特发性肺纤维化和无特发性肺纤维化的肺癌患者中 hTERT 的免疫组化表达差异。
背景:人类端粒酶逆转录酶(hTERT)是端粒酶的催化亚基,它能为端粒添加核苷酸,抵消端粒长度的缩短。端粒维持机制的发展是癌症的标志。另一方面,特发性肺纤维化(IPF)与端粒酶基因突变和端粒缩短有关。目的:研究 hTERT 在合并有 IPF 的肺癌中的表达,并与无纤维化的肺癌进行比较:方法:从18例肺癌并发IPF患者以及18例年龄和性别匹配的无肺纤维化的肺癌对照组中提取诊断性肺癌活检组织。用免疫组化方法研究了 hTERT 的表达。使用 ImajeJ 软件对亚细胞染色强度进行量化。此外,还对所有 36 个病例的两个衰老相关标记物 p16 和 p21 进行了免疫组化检测:结果:两组病例均高表达 hTERT,无显著差异(100% vs 95%,p = 0.521)。两组患者的 p16 和 p21 免疫染色均为阴性或极弱。hTERT 定位在 IPF 肺癌组的中位核强度更高(0.62 vs 0.45,p = 0.016),而胞质强度无显著差异(0.17 vs 0.15,p = 0.463)。结论:hTERT在伴有IPF的肺癌中高表达,但与无IPF的肺癌相比,其定位不同,这意味着致病性不同,需要进一步研究。
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来源期刊
Pulmonology
Pulmonology Medicine-Pulmonary and Respiratory Medicine
CiteScore
14.30
自引率
5.10%
发文量
159
审稿时长
19 days
期刊介绍: Pulmonology (previously Revista Portuguesa de Pneumologia) is the official journal of the Portuguese Society of Pulmonology (Sociedade Portuguesa de Pneumologia/SPP). The journal publishes 6 issues per year and focuses on respiratory system diseases in adults and clinical research. It accepts various types of articles including peer-reviewed original articles, review articles, editorials, and opinion articles. The journal is published in English and is freely accessible through its website, as well as Medline and other databases. It is indexed in Science Citation Index Expanded, Journal of Citation Reports, Index Medicus/MEDLINE, Scopus, and EMBASE/Excerpta Medica.
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