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Ann Thorac Surg 2006;82:1204
© 2006 The Society of Thoracic Surgeons

Original Articles: General Thoracic

Invited commentary

Douglas E. Paull, MDa,d, Katherine Heminger, MSb,c,d, Steven J. Berberich, PhDb,c,d

a Department of Surgery, VA Medical Center, 4100 W Third St, No. 112, Dayton, OH 45428
b Department of Biochemistry and Molecular Biology, VA Medical Center, 4100 W Third St, No. 112, Dayton, OH 45428
c The Center for Genomics Research, Boonshoft School of Medicine, VA Medical Center, 4100 W Third St, No. 112, Dayton, OH 45428
d Wright State University School of Medicine, VA Medical Center, 4100 W Third St, No. 112, Dayton, OH 45428

(Email: douglas.paull{at}wright.edu).

Tsubochi and colleagues [1] present further evidence that molecular markers, in this case cyclooxyenase-2 (COX-2) expression, are useful in the determination of prognosis after resection of non-small cell lung cancer (NSCLC) [1]. In their retrospective study of 219 patients, utilizing immunohistochemical staining of surgical specimens, patients with tumor expression of COX-2 had a worse prognosis. This effect was valid in four patient subgroups: males, age younger than 65 years, adenocarcinoma histology, and stage I disease. Combining COX-2 expression with two additional markers, p53 and Ki-67, yielded only slight additional prognostic value.

As an alternative to immunohistochemical studies analyzing one or several molecular markers, current gene expression profiling using tumor extracted RNA and microarray technology offers the potential to simultaneously characterize multiple genes. Statistical methods, including hierarchical clustering, principal components analysis, and Kernel Cox regression modeling, allow the grouping of patients into "high-risk" and "low-risk" categories from the genetic expression of their tumors and permit the linking of gene expression profiles to survival. Several such studies have already been published in patients with stage I adenocarcinoma of the lung [2].

DNA microarray technology has several limitations to overcome, however, including tumor heterogeneity and laboratory variability. In addition, gene expression does not always correlate with protein expression; thus, approaches involving analysis of proteomic patterns (eg, mass spectrometry) may prove equally informative in stratifying patients with NSCLC.

More sophisticated molecular characterization of tumor samples, whether by immunohistochemical, gene expression, or proteomic methods, will prove useful in the future treatment of lung cancer. Goals of these technologies include identification of high-risk patients with early stage NSCLC who would benefit from adjuvant therapy, selection of specific chemotherapy (gene expression chemosensitivity data banks), and targeted therapies, such as COX-2 inhibition, as suggested by Tsubochi and colleagues and previous authors. Thoracic surgeons, as evidenced by this article, will need to incorporate new molecular information with the more traditional strategies of stage, performance status, comorbidity, and pulmonary function in choosing the best treatment for their individual patients with NSCLC.


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  1. Tsubochi H, Sato N, Hiyama M, et al. Combined analysis of cyclooxygenase-2 expression with p53 and Ki-67 in nonsmall cell lung cancer Ann Thorac Surg 2006;82:1198-1204.[Abstract/Free Full Text]
  2. Beer DG, Kardia SL, Huang CC, et al. Gene-expression profiles predict survival of patients with lung adenocarcinoma Nature Med 2002;8:816-824.[Medline]

Related Article

Combined Analysis of Cyclooxygenase-2 Expression With p53 and Ki-67 in Nonsmall Cell Lung Cancer
Hiroyoshi Tsubochi, Nobuyuki Sato, Misae Hiyama, Mitsuomi Kaimori, Shunsuke Endo, Yasunori Sohara, and Tadashi Imai
Ann. Thorac. Surg. 2006 82: 1198-1204. [Abstract] [Full Text] [PDF]




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