Subcellular expression of c-IAP1 and c-IAP2 in colorectal cancers: relationships with clinicopathological features and prognosis.

The Inhibitor of Apoptosis Protein (IAP) family includes several critical cell death inhibitors, the expression of which could be involved in colorectal carcinogenesis. Among them, c-IAP1 and c-IAP2 expression has never been investigated in colorectal cancer. The present study was designed to determine whether expression of both IAPs was related to pathological parameters and survival in sporadic colon carcinomas. Analysis of five human colon cancer cell lines by both western blotting of cell fractions and immunocytochemistry showed that the two IAPs could be expressed both in the nucleus and in the cytoplasm. Immunohistochemical analysis of a series of 46 sporadic colorectal adenocarcinomas demonstrated that c-IAP1 expression was more frequent in the nucleus (85%), and that c-IAP2 was more often expressed in the cytoplasm (82%). A significant association was identified between a strong lymphoid infiltrate in the stroma and the nuclear expression of c-IAP2 (p = 0.02). No other relationship was observed between IAP expression and pathological features. After adjusting by age and stage, the relative risk of death was lower for cytoplasmic c-IAP1, cytoplasmic c-IAP2, and nuclear c-IAP2 expression. It was higher for nuclear c-IAP1 expression. These associations were not statistically significant, but this work underlines the importance of taking into account the subcellular location of the IAP family members in the evaluation of their prognostic significance.

[1]  N. Carr,et al.  M30 expression demonstrates apoptotic cells, correlates with in situ end-labeling, and is associated with Ki-67 expression in large intestinal neoplasms. , 2009, Archives of pathology & laboratory medicine.

[2]  L. O’Driscoll,et al.  Prognostic importance of survivin in breast cancer , 2003, British Journal of Cancer.

[3]  G. Salvesen,et al.  Apoptosis: IAP proteins: blocking the road to death's door , 2002, Nature Reviews Molecular Cell Biology.

[4]  G. Giaccone,et al.  Expression of X-linked inhibitor of apoptosis as a novel prognostic marker in radically resected non-small cell lung cancer patients. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[5]  A. Cheung,et al.  Anti-apoptotic proteins, apoptotic and proliferative parameters and their prognostic significance in cervical carcinoma. , 2001, European journal of cancer.

[6]  G. Fleuren,et al.  Caspase-3 activity as a prognostic factor in colorectal carcinoma. , 2001, Laboratory investigation; a journal of technical methods and pathology.

[7]  A. Markham,et al.  Immunohistochemical Detection of the Anti-Apoptosis Protein, Survivin, Predicts Survival After Curative Resection of Stage II Colorectal Carcinomas , 2001, Annals of Surgical Oncology.

[8]  S. Moriyama,et al.  Expression of survivin in esophageal cancer: Correlation with the prognosis and response to chemotherapy , 2001, International journal of cancer.

[9]  Y. Takano,et al.  Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. , 2001, Cancer letters.

[10]  J Diebold,et al.  Prognostic significance of survivin expression in diffuse large B-cell lymphomas. , 2000, Blood.

[11]  K. Shiraki,et al.  Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16INK4a and Cdk2/Cyclin E complex activation , 2000, Oncogene.

[12]  A. Markham,et al.  Expression of the antiapoptosis gene,Survivin, predicts death from recurrent colorectal carcinoma , 2000, Gut.

[13]  E Springer,et al.  Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. , 1999, Cancer research.

[14]  E. Felip,et al.  A novel anti-apoptosis gene: Re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  P. Marynen,et al.  The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas. , 1999, Blood.

[16]  X. Sun,et al.  Clinicopathological and genetic characteristics of mucinous carcinomas in the colorectum. , 1999, International journal of oncology.

[17]  J C Reed,et al.  IAP family proteins--suppressors of apoptosis. , 1999, Genes & development.

[18]  Fengzhi Li,et al.  Control of apoptosis and mitotic spindle checkpoint by survivin , 1998, Nature.

[19]  D. Altieri,et al.  Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. , 1998, Cancer research.

[20]  D. Altieri,et al.  Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. , 1998, Cancer research.

[21]  G. Sirugo,et al.  Induction of Apoptosis and Inhibition of Cell Proliferation bysurvivin Gene Targeting* , 1998, The Journal of Biological Chemistry.

[22]  D. Vaux,et al.  Conservation of baculovirus inhibitor of apoptosis repeat proteins (BIRPs) in viruses, nematodes, vertebrates and yeasts. , 1998, Trends in biochemical sciences.

[23]  D. Altieri,et al.  A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma , 1997, Nature Medicine.

[24]  L. Fielding,et al.  College of American Pathologists Conference XXVI on clinical relevance of prognostic markers in solid tumors. Report of the Colorectal Cancer Working Group. , 1995, Archives of pathology & laboratory medicine.

[25]  C. Winterford,et al.  Apoptosis. Its significance in cancer and cancer Therapy , 1994, Cancer.

[26]  J. Diebold,et al.  Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. , 1998, The American journal of pathology.