Invited Commentary

Abstract

The study by Li and associates [1Li Y. Yang H.-X. Luo R.-Z. et al.High expression of p300 has an unfavorable impact on survival in resectable esophageal squamous cell carcinoma.Ann Thorac Surg. 2011; 91: 1531-1538Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar] examines the clinical and prognostic significance of p300 expression, a transcriptional regulator, in resectable esophageal squamous cell cancer. Current oncologic research in a variety of malignancies has increasingly focused on identifying genetic fingerprints of tumors, with significant impact on clinical treatment and outcomes. Such examples include EGFR in lung cancer, BCR-ABL in chronic myelogenous leukemia [2Druker B.J. Sawyers C.L. Kantarjian H. et al.Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome.N Engl J Med. 2001; 344: 1038-1042Crossref PubMed Scopus (2418) Google Scholar], C-Kit inhibition in gastrointestinal stromal tumors [3Demetri G.D. van Oosterom A.T. Garrett C.R. et al.Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.N Engl J Med. 2002; 347: 472-480Crossref PubMed Scopus (3658) Google Scholar], K-Ras in colon cancer [4Khambata-Ford S. Garrett C.R. Meropol N.J. et al.Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.J Clin Oncol. 2007; 25: 3230-3237Crossref PubMed Scopus (1017) Google Scholar, 5Lièvre A. Bachet J.B. Boige V. et al.KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab.J Clin Oncol. 2008; 26: 374-379Crossref PubMed Scopus (1325) Google Scholar], and HER2 blockade in breast cancers [6Slamon D.J. Leyland-Jones B. Shak S. et al.Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.N Engl J Med. 2001; 344: 783-792Crossref PubMed Scopus (9166) Google Scholar]. In addition, research is continuing to identify new molecular markers and genetic targets such as B-RAF in melanoma, ALK in lung cancer, and P13K in breast cancer among others. However, specific molecular markers are not yet available for clinical use in esophageal cancer as there are no reliable markers that provide a true clinical assessment of survival and response to treatment. The current study used tissue microarrays to correlate increased expression of the transcriptional co-activator p300, with higher histologic grade, T status, and lymph node involvement in patients with esophageal squamous cell cancer. The p300 transcriptional regulator, also known as KAT3B/EP300, is involved in DNA repair, cell growth and differentiation, apoptosis, and cell migration, with overexpression linked to poor prognosis in lung, breast, colorectal, and prostate cancers. This association with poor outcomes has now been demonstrated in patients with esophageal squamous cell carcinoma with higher p300 expression and is correlated with poorer disease-free and overall survival, particularly in patients with stage II disease. These findings suggest that there may be clinical utility in assessing p300 levels in selected patient populations. Although a serum marker that can identify and prognosticate patient outcomes without a formal biopsy would be the most useful approach, work such as the identification of p300 expression within tumors is important in establishing the first step toward a better understanding of esophageal cancer and in identifying early biomarkers that may be predictive of patient outcomes in this disease. Clearly, further work is needed in esophageal cancer to identify potential treatment targets—as has been done for breast, lung, and stromal tumors—and to extend prognostic biomarkers to include both squamous and adenocarcinoma histologic characteristics. It is the ultimate goal of personalized medicine to use an array of markers to better understand the pathogenesis, tumor targets, recurrence risk, and metastatic potential so that treatment can truly be individualized to the patient and their specific tumor. High Expression of p300 Has an Unfavorable Impact on Survival in Resectable Esophageal Squamous Cell CarcinomaThe Annals of Thoracic SurgeryVol. 91Issue 5Previewp300 is a transcriptional regulator that is involved in fundamental processes such as cell proliferation, cell differentiation, and tumor progression. However, its role and clinical significance in resectable esophageal squamous cell carcinoma (ESCC) has not been elucidated. The purpose of this study was to explore whether there was a correlation between the expression of p300 by immunohistochemistry and the clinical outcome of a group of patients with ESCC treated with surgical resection. Full-Text PDF