title: Nuclear expression of cIAP-1, an apoptosis inhibiting protein, predicts lymph node metastasis and poor patient prognosis in head and neck squamous cell carcinomas.
abstract: cIAP-1, an apoptosis inhibiting protein, has been suggested to play important roles in the development of cervical and esophageal squamous cell carcinomas (SCCs). In order to clarify the subcellular localization of cIAP-1 and to investigate its clinicopathological significance in head and neck SCCs (HNSCCs), we examined cIAP-1 expression in four oral SCC cell lines by immunocytochemistry and Western blot. Expressions of nuclear and cytoplasmic cIAP-1, caspase-3, and Smac/DIABLO were also examined immunohistochemically in 57 cases of the HNSCCs. cIAP-1 expression was detected in HSC-2, HSC-3, and HSC-4 cells by immunohistochemistry and Western blot. In HSC-2 and HSC-4 cells, cIAP-1 was detected in both the nuclear and cytoplasmic fractions. Nuclear cIAP-1 expression was positive in 17 (30%) of HNSCCs, was correlated with lymph node metastasis (P=0.020) and advanced disease stage (P=0.032), and tended to be correlated with poor patient prognosis (P=0.059). Cytoplasmic cIAP-1 expression showed similar but weaker clinicopathological correlations. Nuclear cIAP-1 expression was inversely correlated with caspase-3 expression, but was correlated with Smac/DIABLO expression. Nuclear cIAP-1 expression appears to be a useful marker for predicting poor patient prognosis in HNSCCs, and may play roles in HNSCCs through the signaling pathway mediated by Smac/DIABLO and caspase-3.
authors.affiliation: Department of Pathology II, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Tanimoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Nobuo
authors.initials: N
authors.lastname: Imazeki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohno
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsubara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D002352:Carrier Proteins / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002467:Cell Nucleus / Q000737:chemistry; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000502:physiology; D011237:Predictive Value of Tests; D011379:Prognosis; D011506:Proteins / Q000032:analysis / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C412403:DIABLO protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases