Expression of the antiapoptotic protein survivin in colon cancer

Jonathan M. Hernandez, Jeffrey M. Farma, Domenico Coppola, Ardeshir Hakam, William J. Fulp, Dung Tsa Chen, Erin M. Siegel, Timothy J. Yeatman, David Shibata

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Abstract

Background: The antiapoptotic protein survivin has been demonstrated to play an important role in colorectal carcinogenesis. However it is unclear whether the upregulation of survivin is maintained through progressive stages of disease, or if other apoptosis-related genes are coexpressed and/or repressed. We sought to evaluate survivin expression in colonic neoplasia and identify relationships with additional regulators of apoptosis. Patients and Methods: Tissue samples from 168 patients with primary colorectal cancer were profiled using the GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) and evaluated for survivin expression. Immunohistochemical staining for survivin and a panel of apoptosis-associated proteins were used in 86 patients with tissue microarray (TMA) blocks; scoring was by stain intensity and percentage of positive cells (range, 0-9). Results: Survivin mRNA was upregulated (1.8-fold increase) in primary colon cancers irrespective of American Joint Committee on Cancer (AJCC) stage and metastases compared with normal colonic tissue (P <.0001). Survivin staining was positive in 93% of adenocarcinomas (median immunohistochemistry [IHC] score: 2 [range, 1-6]), 100% of adenomas (1 [range,1-2]), and 43% of normal colonic mucosa (1, [range 1-2]) (P =.006). Survivin expression increased with worsening tumor grade (P <.05). In colon cancers, survivin expression positively correlated with the coexpression of PUMA (P <.001), TACE (P =.003), and MCL1 (P =.01), and trended toward an inverse correlation with BAX (P =.058). Conclusions: Survivin expression increases during the normal mucosa-adenoma-carcinoma sequence and is maintained throughout progression of disease, which strengthens its appeal as a therapeutic target. Furthermore, we have demonstrated co-overexpression of several other apoptosis-related genes, which may in turn serve as additional and potentially synergistic therapeutic targets.

Original languageEnglish (US)
Pages (from-to)188-193
Number of pages6
JournalClinical Colorectal Cancer
Volume10
Issue number3
DOIs
StatePublished - Jan 1 2011

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Colonic Neoplasms
Apoptosis
Adenoma
Mucous Membrane
Proteins
Staining and Labeling
Neoplasms
Human Genome
Genes
Disease Progression
Colorectal Neoplasms
Carcinogenesis
Adenocarcinoma
Coloring Agents
Up-Regulation
Immunohistochemistry
Neoplasm Metastasis
Carcinoma
Messenger RNA
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Gastroenterology

Cite this

Hernandez, J. M., Farma, J. M., Coppola, D., Hakam, A., Fulp, W. J., Chen, D. T., ... Shibata, D. (2011). Expression of the antiapoptotic protein survivin in colon cancer. Clinical Colorectal Cancer, 10(3), 188-193. https://doi.org/10.1016/j.clcc.2011.03.014

Expression of the antiapoptotic protein survivin in colon cancer. / Hernandez, Jonathan M.; Farma, Jeffrey M.; Coppola, Domenico; Hakam, Ardeshir; Fulp, William J.; Chen, Dung Tsa; Siegel, Erin M.; Yeatman, Timothy J.; Shibata, David.

In: Clinical Colorectal Cancer, Vol. 10, No. 3, 01.01.2011, p. 188-193.

Research output: Contribution to journalArticle

Hernandez, JM, Farma, JM, Coppola, D, Hakam, A, Fulp, WJ, Chen, DT, Siegel, EM, Yeatman, TJ & Shibata, D 2011, 'Expression of the antiapoptotic protein survivin in colon cancer', Clinical Colorectal Cancer, vol. 10, no. 3, pp. 188-193. https://doi.org/10.1016/j.clcc.2011.03.014
Hernandez JM, Farma JM, Coppola D, Hakam A, Fulp WJ, Chen DT et al. Expression of the antiapoptotic protein survivin in colon cancer. Clinical Colorectal Cancer. 2011 Jan 1;10(3):188-193. https://doi.org/10.1016/j.clcc.2011.03.014
Hernandez, Jonathan M. ; Farma, Jeffrey M. ; Coppola, Domenico ; Hakam, Ardeshir ; Fulp, William J. ; Chen, Dung Tsa ; Siegel, Erin M. ; Yeatman, Timothy J. ; Shibata, David. / Expression of the antiapoptotic protein survivin in colon cancer. In: Clinical Colorectal Cancer. 2011 ; Vol. 10, No. 3. pp. 188-193.
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abstract = "Background: The antiapoptotic protein survivin has been demonstrated to play an important role in colorectal carcinogenesis. However it is unclear whether the upregulation of survivin is maintained through progressive stages of disease, or if other apoptosis-related genes are coexpressed and/or repressed. We sought to evaluate survivin expression in colonic neoplasia and identify relationships with additional regulators of apoptosis. Patients and Methods: Tissue samples from 168 patients with primary colorectal cancer were profiled using the GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) and evaluated for survivin expression. Immunohistochemical staining for survivin and a panel of apoptosis-associated proteins were used in 86 patients with tissue microarray (TMA) blocks; scoring was by stain intensity and percentage of positive cells (range, 0-9). Results: Survivin mRNA was upregulated (1.8-fold increase) in primary colon cancers irrespective of American Joint Committee on Cancer (AJCC) stage and metastases compared with normal colonic tissue (P <.0001). Survivin staining was positive in 93{\%} of adenocarcinomas (median immunohistochemistry [IHC] score: 2 [range, 1-6]), 100{\%} of adenomas (1 [range,1-2]), and 43{\%} of normal colonic mucosa (1, [range 1-2]) (P =.006). Survivin expression increased with worsening tumor grade (P <.05). In colon cancers, survivin expression positively correlated with the coexpression of PUMA (P <.001), TACE (P =.003), and MCL1 (P =.01), and trended toward an inverse correlation with BAX (P =.058). Conclusions: Survivin expression increases during the normal mucosa-adenoma-carcinoma sequence and is maintained throughout progression of disease, which strengthens its appeal as a therapeutic target. Furthermore, we have demonstrated co-overexpression of several other apoptosis-related genes, which may in turn serve as additional and potentially synergistic therapeutic targets.",
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AU - Siegel, Erin M.

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