Colorectal carcinoma is the third leading cause of cancerrelated
deaths in the United States. Approximately one-half
of colorectal carcinoma patients already have metastases at
the time of diagnosis. Smad4 is an intracellular transmitter
of TGF-fl signals and its tumor suppressor function is presumed
to reside in its capacity to mediate TGF-J3-induced growth
inhibition. The roles of Smad-4 in colorectal carcinogenesis
are complex and comprise tumor promoting functions particularly
in late stage carcinogenesis. Importantly. functional
inactivation of Smad4 in colon carcinomas frequently occurs
at late stages when tumors acquire invasive and metastatic
capabilities. Placental (P)-cadherin was first identified in
mouse placenta. The intracellular domain of classic cadherins
interacts with various catenin proteins such as h- and gcatenin.
In addition to their adhesive functions, classic cadherins
modulate transduction of signals and activate Rhofamily
GTPases. Therefore, alterations among cadherin molecules
can affect not only the adhesive properties of a cell
but also its signal transduction which can affect many kinds
of cell activities, organ development and tumorigenesis.
Aim of the Work: The purpose of the current study was
to investigate the role of smad-4 and p-cadherin in colorectal
adcnocarcinomas as well as to verify whether they can be
considered as markers of prognostic significance in patients
with colorectal carcinoma.
Patients and Methods: Tissue biopsies were taken from
paraffin-embedded tissue blocks of 60 cases including 10
normal non-neoplastic mucosae, 50 colorectal carcinomas.
Using immunohistochemical technique, antibodies against Pcadherin
and smad-4. were applied to stain the tissue biopsies
used in this study.
Results: Statistically significant inverse correlations were
found between P-cadherin and Smad-4 expressions and different
clinicopathological variables mainly tumor grade,
patient's TNM stage and distant metastasis.
Conclusions: In conclusion, we investigated the significance
of loss of SMAD4 in colorectal cancer; loss of nuclear
and weak cytoplasmic SMAD4 expression is suggestive of
being involved in prognosis of colorectal carcinomas and
explored the possible underlying mechanisms associated with
poor patient's outcome. Our findings suggest that SMAD4 is
a critical prognostic factor. Similarly, on the basis of these
results, t is possible to suggest P-cadherin as an early marker
of poor prognosis. The lack of P-cadherin and Smad-4 expression
could constitute a hallmark of aggressive biological
behavior in colorectal carcinomas.
Key Words: Smad-4 — P-cadherin — Colorectal carcinoma —
Clinicopathological — lmmunohisiochemical |
