New tricks for old biomarkers: thymidylate synthase expression as a predictor of pemetrexed activity in malignant mesothelioma

Our plain-English summary of New tricks for old biomarkers: thymidylate synthase expression as a predictor of pemetrexed activity in malignant mesothelioma, by P.A. Zucali, E. Giovannetti, Y.G. Assaraf, et al (Annals of Oncology, 2010).

The study

• Authors: P.A. Zucali, E. Giovannetti, Y.G. Assaraf, G.L. Ceresoli, G.J. Peters, A. Santoro
• Journal: Annals of Oncology
• Published: 2010;21(7):1560-1561
• Type of article: Letter
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this letter to the editor, the authors commented on a retrospective study by Righi et al. that examined expression of thymidylate synthase (TS) and excision repair cross-complementation group-1 (ERCC1) in patients with malignant pleural mesothelioma (MPM) treated with platinum compounds and pemetrexed. They noted that Righi et al. found no relationship between survival and ERCC1 protein levels. They also noted that Righi et al. reported a correlation between TS mRNA and protein expression but none between TS mRNA and outcome, which was ascribed to the small number of tumor cells in MPM specimens. The authors summarized their own previously reported findings in 71 MPM patients treated with carboplatin plus pemetrexed. TS protein expression correlated with shorter progression-free survival (hazard ratio 1.23; P = 0.004) and overall survival (HR 1.21; P = 0.02). It was also associated with a lower probability of disease control (odds ratio 1.57; P = 0.012), and with progression-free survival (HR 1.24; P = 0.005) in a model corrected for disease control. They argued that immunostaining scoring and quantitative RT-PCR methods need optimization and standardization. They also argued that other determinants of pemetrexed activity, and polymorphisms such as TSER-2R/3R and ERCC1-C118T, should be evaluated. They concluded that standardized methods, larger uniformly treated cohorts and genotype studies were needed before prospective trials could identify the best biomarkers for personalized chemotherapy of MPM.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This was a letter to the editor, not a new study. The authors commented on a study by Righi and colleagues of whether levels of two tumor markers, thymidylate synthase (TS) and ERCC1, related to outcomes in patients with malignant pleural mesothelioma treated with platinum drugs and pemetrexed. As the letter describes it, Righi and colleagues found that TS mRNA and TS protein levels correlated with each other, but TS mRNA did not correlate with outcome. The authors also restated their own earlier findings, presented at a 2009 conference, in 71 malignant pleural mesothelioma patients treated with carboplatin plus pemetrexed. In that group, TS protein expression correlated with shorter progression-free survival (hazard ratio 1.23; P = 0.004) and shorter overall survival (hazard ratio 1.21; P = 0.02). It was also associated with what the authors called a "minor probability" of disease control (odds ratio 1.57; P = 0.012). The authors concluded that such retrospective studies can support future trials. They added that laboratory methods must first be standardized and larger, uniformly treated groups studied. The letter did not address 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: Letter to the editor commenting on another study (Righi et al.), restating the authors' own previously presented retrospective findings
• Who was studied: In the authors' own earlier work: 71 patients with malignant pleural mesothelioma treated with carboplatin plus pemetrexed (presented at ECCO 2009). The letter also discusses patients in the Righi et al. study, for whom it gives no numbers.
• Exposure: Not an asbestos exposure study. The factor studied was tumor thymidylate synthase (TS) protein expression in patients receiving carboplatin plus pemetrexed chemotherapy.
• Main results:
  • In the authors' 71 carboplatin plus pemetrexed-treated malignant pleural mesothelioma patients, TS expression correlated with shorter progression-free survival (HR = 1.23; P = 0.004) and shorter overall survival (HR = 1.21; P = 0.02).
  • In the same group, TS was associated with a "minor probability" of disease control (odds ratio = 1.57; P = 0.012).
  • As described in the letter, the Righi et al. study (not this one) found a correlation between TS mRNA and TS protein expression, but no correlation between TS mRNA and outcome.
• The authors' conclusion: The authors concluded that retrospective studies of candidate predictive biomarkers in mesothelioma specimens can provide a rationale for future trials. They said standardized methods, larger and uniformly treated cohorts, and study of other biomarkers and genotypes are critical before prospective trials can identify the best biomarkers for personalized chemotherapy.
• Limitations the authors state:
  • The authors state that there is no consensus on how to score ERCC1 and TS immunostaining.
  • The authors indicate that final results of their own carboplatin/pemetrexed study were still awaited.
  • The authors state that larger and uniformly treated cohorts are needed.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Pemetrexed (Alimta), Malignant Mesothelioma, Pleural Mesothelioma, Carboplatin, Progression-Free Survival, Hazard Ratio, Overall Survival.

Related studies

• Thymidylate synthase and folyl-polyglutamate synthase are not clinically useful markers of response to pemetrexed in patients with malignant pleural mesothelioma — D.E. Lustgarten, C. Deshpande, et al. (2013)
• Reduced folate carrier and folylpolyglutamate synthetase, but not thymidylate synthase predict survival in pemetrexed-treated patients suffering from malignant pleural mesothelioma — F. Mairinger, C. Vollbrecht, et al. (2013)
• "One marker does not fit all": additional translational and validation studies are needed to identify faithful predictors of pemetrexed activity in mesothelioma — E. Giovannetti, G.J. Peters, et al. (2013)
• The issue of studies evaluating biomarkers which predict outcome after pemetrexed-based chemotherapy in malignant pleural mesothelioma — F. Mairinger, C. Vollbrecht, et al. (2013)
• Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali, et al. (2011)
• 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)

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