¹⁸F-FDG uptake on PET is a predictive marker of thymidylate synthase expression in patients with thoracic neoplasms

Our plain-English summary of ¹⁸F-FDG uptake on PET is a predictive marker of thymidylate synthase expression in patients with thoracic neoplasms, by K. Kaira, N. Yamamoto, M. Endo, et al (Oncology Reports, 2014).

The study

• Authors: K. Kaira, N. Yamamoto, M. Endo, H. Kenmotsu, T. Naito, A. Ono, H. Murakami, Y. Ohde, T. Nakajima, T. Takahashi
• Journal: Oncology Reports
• Published: 2014;31(1):209-15
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The aim of this study was to investigate the relationship between the expression levels of thymidylate synthase (TS) and 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) uptake on positron emission tomography (PET) in various thoracic neoplasms. In total, 392 patients [non-small cell lung cancer (NSCLC) (n=140), malignant pleural mesothelioma (MPM) (n=21), pulmonary metastatic tumors (PMT) (n=148), thymic epithelial tumors (n=49) and pulmonary neuroendocrine (NE) tumor (n=34)] who underwent ¹⁸F-FDG PET before treatment were included in this study. Tumor sections were stained using immunohistochemistry for determination of TS, orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase (DPD), vascular endothelial growth factor (VEGF), microvessel density (MVD), CD34 and p53. The expression of TS in thoracic neoplasms had a positivity of 58% (230/392), and the positive rates of TS expression in NSCLC, PMT, thymic epithelial tumor, NE tumor and MPM samples were 56, 57, 57, 85 and 47%, respectively. The positivity of TS expression was significantly higher in NE tumors compared to that in other thoracic tumors. A statistically significant correlation between TS expression and ¹⁸F-FDG uptake was observed in thoracic neoplasms, in particular primary lung adenocarcinomas, high-grade NE tumors, thymomas and MPMs. Moreover, TS expression was closely associated with angiogenesis, DPD, OPRT and p53. Our results indicated that SUV(max) by ¹⁸F-FDG uptake may be an alternative biomarker for predicting TS expression in patients with primary lung adenocarcinoma, high-grade NE tumor, thymoma and MPM.

In plain English

This study from Shizuoka Cancer Center in Japan examined 392 patients with chest tumors who had an 18F-FDG PET scan before treatment: 140 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. Tumor samples were stained for thymidylate synthase (TS), an enzyme targeted by drugs such as S-1 and pemetrexed, and for other markers. The authors compared TS with how strongly each tumor took up the PET tracer (SUVmax). Overall, 58% (230/392) of tumors were TS-positive, including 47% of mesotheliomas. Neuroendocrine tumors had the highest rate, 85%. TS was correlated with tracer uptake across all tumors and in the 21 mesothelioma patients (Spearman correlation 0.665, 95% confidence interval 0.315 to 0.855, P=0.001). It was not significantly correlated with uptake in squamous cell carcinoma or thymic carcinoma. The authors concluded that SUVmax may be an alternative marker for predicting TS expression in lung adenocarcinoma, high-grade neuroendocrine tumors, thymoma and mesothelioma. The article did not report on 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: Single-center study correlating tumor immunohistochemistry (TS and other markers) with pre-treatment 18F-FDG PET uptake in consecutive patients; Fisher's exact test and Spearman rank correlation
• Who was studied: 392 patients at Shizuoka Cancer Center, Japan (231 male, 161 female; age 16 to 89, median 62). The 140 NSCLC patients were enrolled December 2002 to March 2004. The other groups were drawn from April 2003 to May 2009: 148 pulmonary metastatic tumors, 21 malignant pleural mesothelioma (16 epithelial, 2 biphasic, 1 sarcomatous, 2 unspecified), 34 pulmonary neuroendocrine tumors and 49 thymic epithelial tumors.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The factors compared were 18F-FDG uptake (SUVmax) and tumor TS expression, along with OPRT, DPD, VEGF, CD34/MVD and p53.
• Main results:
  • TS was positive in 58% (230/392) of all tumors
  • TS-positive rates were 56% in primary lung cancer, 57% in pulmonary metastatic tumors, 57% in thymic epithelial tumors, 85% in neuroendocrine tumors and 47% in malignant pleural mesothelioma
  • TS positivity in neuroendocrine tumors (n=34) was significantly higher than in NSCLC (P=0.001), pulmonary metastatic tumors (P=0.001), thymic epithelial tumors (P=0.008) and MPM (P=0.005)
  • Across all 392 patients, positive TS expression was significantly associated with male sex, SUVmax and the expression of OPRT, DPD, VEGF, CD34 and p53
  • In all 392 patients, TS correlated with SUVmax (Spearman 0.464, 95% CI 0.381-0.541, P less than 0.001)
  • In the 21 malignant pleural mesothelioma patients, TS correlated with SUVmax (Spearman 0.665, 95% CI 0.315-0.855, P=0.001)
  • By histology, TS correlated significantly with 18F-FDG uptake in pulmonary adenocarcinoma, high-grade neuroendocrine tumor, thymoma and epithelial-type MPM (n=16: Spearman 0.614, 95% CI 0.153-0.855, P=0.012)
  • In the 58 patients with squamous cell carcinoma, TS was not closely associated with SUVmax or the other markers. In the 11 patients with thymic carcinoma, TS was not closely correlated with 18F-FDG uptake.
• The authors' conclusion: The authors concluded that SUVmax on 18F-FDG PET may be an alternative biomarker for predicting TS expression in primary lung adenocarcinoma, high-grade neuroendocrine tumor, thymoma and MPM. Their final conclusion emphasized primary lung adenocarcinoma.
• Limitations the authors state:
  • The authors stated that further study is needed to determine whether SUVmax predicts outcome after S-1 or pemetrexed treatment. The study did not examine treatment outcome.

Topics

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

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• PET scan contribution in chest tumor management: a systematic review for thoracic surgeons — L. Duranti, F. Leo, et al. (2012)

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