A somatic TSHR mutation in a patient with lung adenocarcinoma with bronchioloalveolar carcinoma, coronary artery disease and severe chronic obstructive pulmonary disease

Our plain-English summary of A somatic TSHR mutation in a patient with lung adenocarcinoma with bronchioloalveolar carcinoma, coronary artery disease and severe chronic obstructive pulmonary disease, by J.W. Kim, S. Lee, N. Lui, et al (Oncology Reports, 2012).

The study

• Authors: J.W. Kim, S. Lee, N. Lui, H. Choi, M. Mulvihill, L.T. Fang, H.C. Kang, Y.W. Kwon, D. Jablons, I.J. Kim
• Journal: Oncology Reports
• Published: 2012;28(4):1225-30
• Type of article: Case report
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In a screen for thoracic malignancy-associated markers, thyroid stimulating hormone receptor (TSHR) was identified as a candidate as it binds to the previously-characterized lung cancer marker NKX2-1. We screened for mutations in all coding regions of the TSHR gene in 96 lung adenocarcinoma samples and their matched adjacent normal lung samples. We found one patient with a somatic mutation at codon 458 (exon 10), which is located at the transmembrane domain where most TSHR mutations have been found in thyroid-related diseases. This patient had lung adenocarcinoma with BAC (bronchioloalveolar carcinoma) features in the setting of a prior medical history significant for carotid stenosis and severe chronic obstructive pulmonary disease (COPD). In order to characterize the genetic features of TSHR in lung cancer, we checked for TSHR expression and copy number in the 96 lung cancer tissues. TSHR protein expression was generally overexpressed in multiple thoracic malignancies (adenocarcinoma, squamous cell carcinoma and malignant pleural mesothelioma) by immunohistochemistry. Our data suggest that aberrant TSHR function may contribute to lung cancer development or a subgroup of lung cancer with specific clinical phenotypes.

In plain English

This laboratory study used tumor tissue from patients at the University of California San Francisco. It did not study asbestos or any other workplace exposure. The authors searched the TSHR gene (thyroid stimulating hormone receptor) for mutations in 96 lung adenocarcinoma samples and in matched normal lung samples from the same patients. They found one mutation, present in the tumor but not in the normal tissue, a frequency of 1%. That patient was a 67-year-old woman with coronary artery disease, carotid stenosis, chronic obstructive pulmonary disease (COPD) and a 50-pack-year smoking history. Her tumor showed features of bronchioloalveolar carcinoma. TSHR messenger RNA levels did not differ significantly between tumor and normal tissue (p=0.118). Among the 96 tumors there were two possible gene gains and two deletions. Staining showed high TSHR protein in adenocarcinoma and squamous cell carcinoma samples, with low or mild staining in matched normal tissue. For malignant pleural mesothelioma only tumor samples were stained, and they showed high TSHR. The authors concluded that TSHR mutation is not a major event in lung cancer generally. They said larger studies are needed to test whether certain patient subgroups may be susceptible to a TSHR mutation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory genetic study of tumor and matched normal tissue (mutation screening, mRNA expression, DNA copy number, immunohistochemistry), with a description of the one patient found to carry a mutation
• Who was studied: 96 lung adenocarcinoma samples with matched normal lung tissue from patients with thoracic malignancies at UCSF, used in the authors' previous study. Immunohistochemistry was done on ten pairs of matched normal and lung adenocarcinoma and squamous cell carcinoma, and on five malignant pleural mesothelioma samples. Dates of collection are not given.
• Exposure: No asbestos or other occupational exposure was studied. The study examined changes in the TSHR gene and its expression in tumor tissue. The one patient with the mutation had a 50-pack-year smoking history.
• Main results:
  • One somatic TSHR mutation (exon 10, codon 458, F458I) was found among the 96 lung adenocarcinoma samples, a mutation frequency of 1%
  • The patient with the mutation had stage IB adenocarcinoma with features of bronchioloalveolar carcinoma at her second operation and no signs or symptoms of thyroid disease
  • TSHR mRNA expression did not differ significantly between the 96 tumor samples and their matched normal tissues (paired t-test p=0.118)
  • DNA copy number analysis found two potential amplifications and two deletions of TSHR among the 96 adenocarcinoma samples
  • In the patient with the mutation, both TSHR and NKX2-1 (TTF1) protein were generally overexpressed in tumor compared with normal tissue
  • High TSHR protein expression was found in adenocarcinoma and squamous cell carcinoma samples, with low or mild expression in matched normal samples
  • For malignant pleural mesothelioma, only tumor samples were stained, and high TSHR expression was detected
• The authors' conclusion: The authors concluded that, with a mutation frequency of about 1% (1/96), TSHR mutation is not a major event in lung carcinogenesis generally. They suggested that TSHR protein might be useful for diagnostic or therapeutic purposes and that certain subgroups may be susceptible to a TSHR mutation.
• Limitations the authors state:
  • The authors stated that further studies with larger numbers of samples are required before concluding that a subgroup of patients (such as those with BAC, COPD and/or cardiovascular disease) may be susceptible to a TSHR mutation
  • The authors stated that a larger systematic study is needed to validate a possible role of TSHR in BAC-type adenocarcinoma in patients with pre-existing COPD

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Adenocarcinoma, Carcinoma, Lung Cancer, Somatic Mutation, COPD, Adenocarcinoma, Squamous Cell Carcinoma, Pleural Mesothelioma.

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