Abstract
Background
AAA+ nuclear coregulator cancer associated (ANCCA) is found to be overexpressed in various cancer types and could play a role in common and fundamental cellular processes. A recent study suggested that ANCCA was a likely driver whose expression explained the behavior of differentially expressed proliferation-related genes in lung adenocarcinoma. However, protein expression of ANCCA in lung adenocarcinoma and its association with clinicopathologic parameters and commonly reported driver mutations remains unexplored.
Methods
ANCCA expression was evaluated by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinicopathologic and molecular variables including adenocarcinoma histologic subtypes, tumor, node, metastasis status, relapse-free survival, overall survival, EGFR mutations, KRAS mutations, HER2 mutations and ALK fusions.
Results
Positive ANCCA expression was significantly associated with male sex, smokers, poorly differentiated tumors, nonlepidic predominant subtype, more advanced T stage, lymph nodal metastasis and late disease stage. Cox multivariate analysis revealed that ANCCA-positive expression was an independent predictor of worse relapse-free survival [hazard ratio (HR) 1.736, 95 % confidence interval (CI) 1.075–2.804; P = .024) and overall survival (HR 7.758, 95 % CI 2.955–20.370; P < .001). The addition of ANCCA protein expression to the prognostic model using pathologic stage markedly improved the prognostic accuracy; the concordance index increased from .692 to .788, and the Akaike information criterion decreased from 354.20 to 336.11.
Conclusions
We have identified ANCCA protein expression as a novel independent poor prognostic indicator in lung adenocarcinoma. Prospective studies are warranted to validate its potential prognostic value in combination with the current staging system.
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References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Al-Kattan K, Sepsas E, Fountain SW, Townsend ER. Disease recurrence after resection for stage I lung cancer. Eur J Cardiothorac Surg. 1997;12:380–4.
Zhu CQ, Shih W, Ling CH, Tsao MS. Immunohistochemical markers of prognosis in non–small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J Clin Pathol. 2006;59:790–800.
Ciro M, Prosperini E, Quarto M, et al. ATAD2 is a novel cofactor for MYC, overexpressed and amplified in aggressive tumors. Cancer Res. 2009;69:8491–8.
Zou JX, Revenko AS, Li LB, Gemo AT, Chen HW. ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERalpha, is required for coregulator occupancy and chromatin modification. Proc Natl Acad Sci USA. 2007;104:18067–72.
Zou JX, Guo L, Revenko AS, et al. Androgen-induced coactivator ANCCA mediates specific androgen receptor signaling in prostate cancer. Cancer Res. 2009;69:3339–46.
Caron C, Lestrat C, Marsal S, et al. Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers. Oncogene. 2010;29:5171–81.
Fouret R, Laffaire J, Hofman P, et al. A comparative and integrative approach identifies ATPase family, AAA domain containing 2 as a likely driver of cell proliferation in lung adenocarcinoma. Clin Cancer Res. 2012;18:5606–16.
Detre S, Saclani Jotti G, Dowsett M. A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol. 1995;48:876–8.
Wang R, Pan Y, Li C, et al. The use of quantitative real-time reverse transcriptase PCR for 5′ and 3′ portions of ALK transcripts to detect ALK rearrangements in lung cancers. Clin Cancer Res. 2012;18:4725–32.
Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest. 2009;136:260–71.
Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6:244–85.
Harrell FE Jr, Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. JAMA. 1982;247:2543–6.
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Yang Zhang and Yihua Sun contributed equally to this study.
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Zhang, Y., Sun, Y., Li, Y. et al. ANCCA Protein Expression is a Novel Independent Poor Prognostic Marker in Surgically Resected Lung Adenocarcinoma. Ann Surg Oncol 20 (Suppl 3), 577–582 (2013). https://doi.org/10.1245/s10434-013-3027-1
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DOI: https://doi.org/10.1245/s10434-013-3027-1