title: Smac/DIABLO expression in human gastrointestinal carcinoma: Association with clinicopathological parameters and survivin expression.
abstract: Lack of apoptosis is a key factor in carcinogenesis and tumor progression. Survivin is a member of the inhibitor of apoptosis protein (IAP) family. Second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) is an antagonist of IAPs. Recently, Smac/DIABLO was identified as a potent therapeutic target. However, the clinical significance of Smac/DIABLO in gastrointestinal carcinomas remains unclear. In the present study, Smac/DIABLO expression was analyzed by immunohistochemistry in 72 gastric adenocarcinomas and 78 colorectal adenocarcinomas. The expression of Smac/DIABLO was significantly higher in colorectal carcinoma than in gastric carcinoma. Additionally, a correlation was found between the expression of Smac/DIABLO and nuclear survivin in well- to moderately-differentiated colorectal adenocarcinomas (r=0.245; P<0.01). Based on these results, it was hypothesized that gastric and colorectal carcinomas differ in the level of Smac/DIABLO expression. Our previous studies revealed that the expression of cleaved caspase-9 was significantly lower in colorectal carcinoma than in gastric carcinoma (P<0.0001). Conversely, the expression levels of microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker, and survivin were significantly higher in colon cancer than in gastric cancer (P<0.0001 and P<0.01, respectively). Taken together, these results indicate that not only LC3 and survivin expression, but also Smac/DIABLO expression, are significantly higher in colorectal carcinoma than in gastric carcinoma. We hypothesize that the analysis of Smac/DIABLO, survivin and LC3 expression in colorectal carcinoma is likely to aid cancer therapy due to the involvement of these markers in apoptosis and/or autophagy.
authors.affiliation: Laboratory of Pathology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654-0142, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Shintani
authors.affiliation: Laboratory of Pathology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654-0142, Japan ; Department of Diagnostic Pathology, Osaka Red Cross Hospital, Osaka 543-8555, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sangawa
authors.affiliation: Department of Clinical Laboratory, Kuma Hospital, Kobe, Hyogo 650-0011, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamao
authors.affiliation: Laboratory of Pathology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654-0142, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kamoshida
keywords: Smac/DIABLO; apoptosis; immunohistochemistry; survivin