Programmed cell death 4 protein in esophageal cancer.
Screening for genes down-regulated in esophageal cancers (Oncomine database) pinpointed programmed cell death 4 (PDCD4) as one of the most consistently involved. PDCD4 is a new putative tumor suppressor gene implicated in cell transformation, tumorigenesis, and invasiveness. Based on such a biological rationale, the aim of the present study was to evaluate the prognostic value of PDCD4 in esophageal cancers. The immunohistochemical expression of PDCD4 protein was assessed in 111 consecutive esophageal cancers (63 adenocarcinomas and 48 squamous cell carcinomas) and paired non-cancerous samples. PDCD4 immunostaining was significantly lower in cancer samples than in non-cancerous mucosa (p<0.001). In all cases, the native esophageal epithelium consistently expressed nuclear PDCD4, which was significantly less expressed (37/111 cases) or completely lacking (31/111 cases) in the cancer samples. A significant inverse correlation emerged between nuclear PDCD4 expression and tumor stage (p=0.002), pT (p<0.001), nodal metastasis (p=0.038), and with both vascular (p=0.005) and perineural invasion (p=0.004). Nuclear PDCD4 expression was associated with a longer disease-free (p=0.011) and overall (p=0.021) survival. PDCD4 expression predicts the patient outcome in esophageal cancers. Additional functional studies should look into the role of PDCD4 in the multistep process of esophageal oncogenesis also inquiring on the clinical usefulness of the protein expression as prognostic marker in esophageal precancerous lesions.
Department of Medical Diagnostic Sciences and Special Therapies, University of Padova, Padova (PD), I-35100, Italy.
Matteo
M
Fassan
Matteo
M
Cagol
Gianmaria
G
Pennelli
Christian
C
Rizzetto
Luciano
L
Giacomelli
Giorgio
G
Battaglia
Giovanni
G
Zaninotto
Ermanno
E
Ancona
Alberto
A
Ruol
Massimo
M
Rugge
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000175:diagnosis / Q000378:metabolism; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins