Original article
General thoracic
Maximal Standardized Uptake Value on FDG-PET Is Correlated With Cyclooxygenase-2 Expression in Patients With Lung Adenocarcinoma

https://doi.org/10.1016/j.athoracsur.2011.10.033Get rights and content

Background

Cyclooxygenase-2 (COX-2) is constitutively overexpressed in a variety of epithelial malignancies and is usually associated with a poor prognosis. Fluorodeoxyglucose positron emission tomography (FDG-PET) has become an important tool for the diagnosis and staging of non–small-cell lung cancer. The maximal standardized uptake values (SUVmax) of primary tumors on FDG-PET have been shown to be correlated with some clinicopathologic factors. In this study, we investigated the prediction of intratumoral COX-2 expression by FDG-PET in cases of lung adenocarcinoma.

Methods

We conducted a retrospective review of the data of 60 patients with lung adenocarcinoma measuring less than 3 cm in diameter. Immunohistochemical staining for COX-2 and other biological factors that might influence cancer progression was performed, and the correlations of the selective tumor marker expression with the SUVmax were evaluated.

Results

A significant correlation was observed between the SUVmax and the expressions of COX-2, Ki-67, and vascular endothelial growth factor (VEGF). Multiple stepwise regression analysis revealed significant relationships between the SUVmax and the expression of COX-2 (p < 0.001) and Ki-67 (p = 0.016). Of the 2, COX-2 expression was the stronger determinant of the SUVmax, which increased in proportion to the score for COX-2 expression. The recurrence-free survival of patients with elevated COX-2 expression was significantly worse than that of patients not showing COX-2 expression.

Conclusions

The expression of COX-2 in primary tumors is as strongly correlated with a worse clinical outcome as is increased FDG uptake in cases of lung adenocarcinoma. These findings indicate that the SUVmax of primary tumors might reflect the biological malignant potential in lung adenocarcinomas.

Section snippets

Study Population

Sixty patients with lung adenocarcinomas measuring less than 3 cm in diameter who underwent surgical resection (lobectomy or segmentectomy) with systematic lymph node dissection at Kawasaki Medical School Hospital between 2007 and 2009 were enrolled in this study. None of the patients had received either radiotherapy or chemotherapy before the surgery. The histologic diagnosis of the tumors was based on the criteria of the World Health Organization, and the TNM stage was determined according to

Clinical Characteristics

The characteristics of the patients are summarized in Table 2. The patients ranged in age from 46 to 83 years (mean, 66.8 years). There were 29 men and 31 women. The median value of the SUVmax of all the tumors was 5.9 ± 5.2 (range, 0 to 18.1). No statistically significant association was observed between the SUVmax of primary tumors and the age, sex, or smoking status of the patients. A statistically significant correlation was observed between the SUVmax and the degree of tumor

Comment

The SUV measured on FDG-PET is a semiquantitative value that indicates the degree of glucose uptake in a lesion. The SUVmax of primary lung nodules has been reported to be helpful in distinguishing between malignant and benign tumors, based on the relatively higher values in malignant tumors [27]. We speculated that tumors showing higher SUVmax might be more aggressive and have a higher proliferation potential. We examined this hypothesis by studying the correlation between the SUVmax and the

References (37)

  • H. Nakayama et al.

    Sublobar resection for patients with peripheral small adenocarcinomas of the lung: surgical outcome is associated with features on computed tomographic imaging

    Ann Thorac Surg

    (2007)
  • D.E. Griswold et al.

    Constitutive cyclooxygenase (COX-1) and inducible cyclooxygenase (COX-2): rationale for selective inhibition and progress to date

    Med Res Rev

    (1996)
  • R.N. Dubois et al.

    Cyclooxygenase in biology and disease

    FASEB J

    (1998)
  • T. Hida et al.

    Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas

    Cancer Res

    (1998)
  • D. Hwang et al.

    Expression cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer

    J Natl Cancer Inst

    (1998)
  • S. Ogino et al.

    Cyclooxygenase-2 expression is an independent predictor of poor prognosis in colon cancer

    Clin Cancer Res

    (2008)
  • Y.C. Ung et al.

    18Fluorodeoxyglucose positron emission tomography in the diagnosis and staging of lung cancer: a systematic review

    J Natl Cancer Inst

    (2007)
  • H.Q. Woodard et al.

    Expression of tissue isotope distribution

    J Nucl Med

    (1975)
  • Cited by (10)

    • Cox-2 in non-small cell lung cancer: A meta-analysis

      2013, Clinica Chimica Acta
      Citation Excerpt :

      Results of the search strategy for studies are summarized in Fig. 1. We selected 34 potentially relevant publications [7–10,15–44]. One article was excluded because patients who used anti-cox-2 drugs may have expressed Cox-2 significantly [33]; 1 article was excluded because it demonstrated the prognostic value of COX-2 on recurrence-free survival (rather than OS) for patients with lung ADC [30]; 2 articles were excluded because they demonstrated the prognostic value of COX-2 on progression-free survival (not OS) for patients with NSCLC [31,32]; and 11 studies were excluded because they could not provide the available survival data to calculate HR [34–44].

    • Invited commentary

      2012, Annals of Thoracic Surgery
    View all citing articles on Scopus
    View full text