¹⁸F-FDG uptake on PET could be a predictive marker of excision repair cross-complementation group 1 (ERCC1) expression in patients with thoracic neoplasms?

Our plain-English summary of ¹⁸F-FDG uptake on PET could be a predictive marker of excision repair cross-complementation group 1 (ERCC1) expression in patients with thoracic neoplasms?, by K. Kaira, M. Endo, T. Shukuya, et al (Neoplasma, 2012).

The study

• Authors: K. Kaira, M. Endo, T. Shukuya, H. Kenmotsu, T. Naito, A. Ono, A. Tsuya, Y. Nakamua, T. Takahashi, H. Murakami, H. Kondo, T. Nakajima, N. Yamamoto
• Journal: Neoplasma
• Published: 2012;59(3):257-63
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The aim of this study is to examine the relationship between the expression level of excision repair cross-complementation group 1 (ERCC1) and of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) in various thoracic neoplasm.Three hundreds-eight patients [non-small cell lung cancer (NSCLC)(n=56), malignant pleural mesothelioma (MPM)(n=21), pulmonary metastatic tumors (PMT)(n=148), thymic epithelial tumors (n=49) and pulmonary neuroendocrine tumor (n=34)] who underwent 18F-FDG PET before treatment were included in this study. Tumors sections were stained by immunohistochemistry for ERCC1, glucose transporter 1(Glut1), vascular endothelial growth factor (VEGF) and microvessel density (MVD) by determinate by CD34. The expression of ERCC1 in thoracic neoplasms had a positivity of 49% (152/308), and the positive rates of ERCC1 expression in NSCLC, PMT, thymic epithelial tumor, pulmonary neuroendocrine tumor and MPM were 52, 43, 53, 47 and 85%, respectively. The positivity of ERCC1 expression was significantly higher in MPM and SQC than in the other histological types. A statistically significant correlation between ERCC1 expression and 18F-FDG uptake was observed in thymic epithelial tumors, especially thymoma. Moreover, ERCC1 expression was also closely associated with the expression of Glut1, VEGF and MVD.Our results indicated that 18F-FDG uptake may be an alternative biomarker for predicting ERCC1 expression in patients with thymoma.

In plain English

This retrospective study from Shizuoka Cancer Center in Japan looked at 308 patients with chest tumors, including 21 with malignant pleural mesothelioma. All had a PET scan with the tracer 18F-FDG before treatment. The authors asked whether tracer uptake on the scan tracked the tumor level of ERCC1, a protein linked to resistance to platinum chemotherapy. ERCC1 was found in 49% (152/308) of tumors and in 85% of the mesotheliomas, a rate significantly higher than in the other disease groups. Across all patients, ERCC1 and tracer uptake showed a weak but statistically significant correlation. The correlation was stronger in thymic tumors, especially thymoma, and was also significant in neuroendocrine tumors. It was not statistically significant in mesothelioma. The authors concluded that PET uptake may be an alternative marker for ERCC1 in thymoma. They said it remains unknown whether ERCC1 in mesothelioma relates to chemotherapy resistance. As limitations, they noted the retrospective design and that only some patients received platinum treatment. The study did not examine asbestos exposure.

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: Retrospective clinicopathological study. Tumor tissue was stained for ERCC1, Glut1, VEGF and CD34 (a measure of small blood vessel density) and compared with 18F-FDG PET uptake (SUVmax).
• Who was studied: 308 patients (187 male, 121 female) treated at Shizuoka Cancer Center, Japan, from April 2003 to May 2009. The groups were 56 with non-small cell lung cancer, 21 with malignant pleural mesothelioma, 148 with tumors that had spread to the lung from elsewhere, 49 with thymic epithelial tumors and 34 with pulmonary neuroendocrine tumors. Of the 21 mesotheliomas, 16 were epithelial type, 2 biphasic, 1 sarcomatous and 2 unspecified.
• Exposure: Not an exposure study. The article measured tumor protein levels and PET tracer uptake. It did not study asbestos or any fiber exposure.
• Main results:
  • ERCC1 was positive in 49% (152/308) of all tumors.
  • In malignant pleural mesothelioma, the ERCC1-positive rate (85%) was significantly higher than in the other disease groups.
  • ERCC1 was positive in 88% (14/16) of epithelial-type mesotheliomas and 85% (22/26) of squamous cell carcinomas. These rates were significantly higher than in adenocarcinoma (38%, 55/144), high-grade neuroendocrine tumors (50%, 14/28), sarcoma (50%, 10/20) and thymoma (37%, 15/38).
  • In all 308 patients, ERCC1 correlated weakly with PET uptake (Spearman coefficient 0.154, 95% CI 0.039 to 0.264, p=0.006).
  • In thymic epithelial tumors (n=49), ERCC1 correlated with PET uptake (coefficient 0.723, 95% CI 0.549 to 0.837, p less than 0.001).
  • In thymoma (n=38), ERCC1 correlated with PET uptake (coefficient 0.544, 95% CI 0.262 to 0.740, p less than 0.001).
  • In malignant pleural mesothelioma (n=21), the correlation between ERCC1 and PET uptake was not statistically significant (coefficient 0.231, 95% CI -0.236 to 0.611, p=0.314).
  • Positive ERCC1 was significantly associated with a primary tumor site in the chest and with Glut1, VEGF and CD34 expression.
• The authors' conclusion: The authors concluded that 18F-FDG PET uptake may be an alternative marker for ERCC1 expression in thymoma, and that ERCC1 is highly expressed in mesothelioma and squamous cell carcinoma. For mesothelioma, they stated it remains unknown whether ERCC1 level relates to resistance to platinum-based chemotherapy.
• Limitations the authors state:
  • The analysis was retrospective and mixed patients who did and did not receive platinum treatment, so it gave no information on cisplatin sensitivity.
  • The authors stated there is no apparent rationale for the link they found between ERCC1 and hypoxia and blood-vessel markers, and that further study is needed to confirm it.

Topics

Medical terms in this study, explained in our Lexicon: Neoplasm, Non-Small Cell Lung Cancer, Pleural Mesothelioma, Immunohistochemistry, GLUT1, CD34, Biomarker.

Related studies

• ¹⁸F-FDG uptake on PET is a predictive marker of thymidylate synthase expression in patients with thoracic neoplasms — K. Kaira, N. Yamamoto, et al. (2014)
• Importance of excision repair cross-complementation group 1 and ribonucleotide reductase M1 as prognostic biomarkers in malignant pleural mesothelioma treated with platinum-based induction chemotherapy followed by surgery — L. Frischknecht, M. Meerang, et al. (2015)
• [18F]Fluorodeoxyglucose PET in Thoracic Malignancies — M.H. Vilstrup, D.A. Torigian (2014)
• PET scan contribution in chest tumor management: a systematic review for thoracic surgeons — L. Duranti, F. Leo, et al. (2012)
• Relationship between 18F-FDG uptake on positron emission tomography and molecular biology in malignant pleural mesothelioma — K. Kaira, M. Serizawa, et al. (2012)
• Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival — Z.G. Zimling, J.B. Sørensen, et al. (2012)

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