SMAD4/DPC4 expression and prognosis in human colorectal cancer.
BACKGROUND
Colorectal cancer (CRC) is one of the most common malignancies in Western countries. One major event during CRC development is loss of genetic material on chromosome 18, on which the smad4/dpc4 gene is located. SMAD4 is an important mediator of intracellular signaling in the TGF-beta pathway. The functional inactivation of SMAD4 has been reported to occur in CRC.


METHODS
The protein expression of SMAD4 was evaluated immunohistochemically in 86 formalin-fixed and paraffin-embedded CRC samples. The results were related to clinicopathological variables including survival.


RESULTS
The loss of nuclear SMAD4 protein expression was observed in 9.3% of the investigated CRCs and was correlated to poor prognosis in univariate Kaplan-Meier (p=0.034) as well as in multivariate Cox-regression (p=0.028) analyses.


CONCLUSIONS
The loss of nuclear SMAD4 protein expression occurs in a subset of CRC and is associated with poor prognosis.
Isaksson-Mettävainio
Martin
M
Department of Medical Biosciences, Umeå University, Sweden.
Palmqvist
Richard
R
Forssell
Johan
J
Stenling
Roger
R
Oberg
Ake
A
D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015398:Signal Transduction; D051901:Smad4 Protein / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000378:metabolism
C497796:SMAD4 protein, human; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta