Prognostic value of c-FLIPL/s, HIF-1α, and NF-κβ in stage II and III rectal cancer.
Locally advanced rectal cancer (LARC) is associated with a 25 % rate of metastases. The prognostic and predictive relevances of the expression of five proteins (c-FLIPL/s, HIF-1α, β-catenin, p65, and p105/p50 NF-κβ) were assessed. This is a retrospective study. From 1998 to 2009, 152 patients with stage II/III rectal cancer were treated with radio-chemotherapy. TMAs constructed with tumor and normal tissue from the diagnostic endoscopic biopsy and the surgical specimen after chemoradiotherapy were subjected to immunohistochemical (IHC) analysis. Results were correlated with clinical and pathological data, including progression-free survival (PFS). Four different IHC conditions were independent prognostic parameters for PFS: (1) cytoplasmic c-FLIPL/s (p = 0.007), (2) nuclear HIF-1α (p = 0.020), (3) a change in the cytoplasmic p65 between the diagnostic biopsy and the post-treatment specimen (p = 0.004), and (4) a change in the cytoplasmic c-FLIPL/s between the diagnostic biopsy and the post-treatment specimen (p = 0.021). Three different protein expression profiles, combining biomarkers, showed prognostic significance. IHC evaluation of these biomarkers in our three protein expression profiles may help to identify patients with worse prognosis and design more effective therapeutic strategies to personalize the treatment of rectal cancer.
Departments of Pathology and Medical Oncology, Hospital Universitari Arnau de Vilanova. Universitat de Lleida, IRBLleida, Av. Rovira Roure, 80, 25198, Lleida, Spain.
Anna
A
Novell
Montserrat
M
Martínez-Alonso
Moises
M
Mira
Jordi
J
Tarragona
Antonieta
A
Salud
Xavier
X
Matias-Guiu
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000032:analysis / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000096:biosynthesis*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis / Q000096:biosynthesis*; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D012189:Retrospective Studies; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B