Expression patterns and prognostic significance of inhibitor of apoptosis proteins in adenoid cystic carcinoma and pleomorphic adenoma of lachrymal gland

Exp Eye Res. 2009 Jan;88(1):4-11. doi: 10.1016/j.exer.2008.09.015. Epub 2008 Oct 9.

Abstract

It has been widely reported that IAPs family are overexpressed in various malignancies, and their expression patterns are associated with clinical outcome of these diseases. Adenoid cystic carcinoma (ACC) of lachrymal gland is a malignant tumor with a poor prognosis, while, pleomorphic adenoma (PA) is the benign tumor of lachrymal gland epithelia. It was the first time that we investigated the expression profile of IAPs in tissues from ACC and PA, and evaluated the prognostic significance of IAPs. Paraffin-embedded tissues with 27 cases of ACC and 33 cases of PA were enrolled, and another 17 fresh frozen tissues were also collected. Expression of cIAP1, cIAP2, XIAP, Survivin and Livin in embedded tissues was analyzed by immunohistochemistry, and expression of five IAPs in fresh tissues was evaluated by semiquantitive RT-PCR and Western blot. Prognostic significance of IAPs with clinicopathological variables and outcome was then investigated with univariate and multivariate analysis. Survivin and cIAP2 expression in ACC were significantly higher than that of in PA (p < 0.05). cIAP1 and XIAP tended to show stronger expression in ACC than in PA, although the differences were not statistically significant. Livin expression was almost undetectable in both malignancy and benign lesion of lachrymal gland. Survivin expression in lachrymal tumors was localized in cytoplasm exclusively, and its expression was related to T staging and proliferative index in ACC, multivariate analysis demonstrated that Survivin was the only factor that could independently predict poor prognosis of ACC (RR = 3.681, 95%CI: 1.068-12.688, p = 0.039). Furthermore, Survivin expression was associated with progression of PA. Expression of cIAP1, cIAP2, XIAP and Survivin was higher in ACC than in PA tissues, however, only differential expression of Survivin and cIAP2 between ACC and PA was significant. Different prognosis between ACC and PA might be attributable to the different expression profiles of IAPs. Overexpression of Survivin in ACC was associated with poorer survival, which may have clinical impact on diagnosis and therapeutic considerations of this malignancy.

MeSH terms

  • Adenoma, Pleomorphic / metabolism*
  • Adenoma, Pleomorphic / pathology
  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Adenoid Cystic / metabolism*
  • Carcinoma, Adenoid Cystic / pathology
  • Gene Expression
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Lacrimal Apparatus Diseases / metabolism*
  • Lacrimal Apparatus Diseases / pathology
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Paraffin Embedding
  • Prognosis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Survival Analysis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins
  • RNA, Messenger