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

Thoracic Oncology Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
Oncology Reports (Impact Factor: 2.3). 07/2012; 28(4):1225-30. DOI: 10.3892/or.2012.1938
Source: PubMed


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.

Full-text preview

Available from:
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Thyroid-stimulating hormone (TSH) regulates normal thyroid function by binding to its receptor (thyroid-stimulating hormone receptor -TSHR) that is expressed at the surface of thyroid cells. Recently, it has been demonstrated that TSHR is abundantly expressed in several tissues apart from the thyroid, among them the normal ovarian surface epithelium. The role of TSHR expression outside the thyroid is not completely understood. The current study examines possible alterations of TSHR expression in ovarian carcinomas and its implication in ovarian carcinogenesis. Materials and methods: Quantitative real-time polymerase chain reaction and immunohistochemistry analysis of TSHR expression were performed in 34 ovarian carcinoma specimens and 10 normal ovarian tissues (controls). Results: Significant reduction in TSHR messenger RNA (mRNA) expression was detected in ovarian carcinomas (mean [SD]: 0.518 [0.0934] vs normal, 49.4985 [89.1626]; P < 0.001, Mann-Whitney U test), whereas TSHR protein levels were significantly increased (percentage of positive cells: cancer, 73.55% [20.09%], vs normal, 54.54% [21.14%]; intensity: cancer, 2.52 [0.508], vs normal 1 [0]; P = 0.012, Mann-Whitney U test). No significant differences in TSHR mRNA were found according to history of thyroid disease. Conclusions: Our study describes for the first time alterations in TSHR expression both at mRNA and protein levels in ovarian carcinomas. The discrepancy between the decreased levels of the TSHR mRNA and the increased protein expression has already been described in thyroid carcinomas and might be due to alterations in its degradation by the ubiquitin system or other unknown mechanisms. Further analysis could elucidate the role of these findings in ovarian carcinogenesis.
    No preview · Article · Jun 2014 · International Journal of Gynecological Cancer