Overexpression of SMAD7—a hallmark inhibitor of transforming growth factor β (TGFβ)
signaling—has been documented and related with adverse prognosis in a number of epithelial
malignancies, suggesting that it may be responsible for resistance to TGFβ-induced
growth arrest of cancer cells. The involvement of SMAD7 in development and progression
of malignant melanoma is unclear, and its expression has not been characterized so
far at the protein level in clinical melanoma tissue samples. We evaluated SMAD7 expression
in 205 skin melanoma primary tumors by immunohistochemistry and correlated the findings
with clinicopathological profiles of patients. Melanocytic SMAD7 was evidenced in
204 cases, and the expression pattern was predominantly nuclear. High expression of
SMAD7 was positively associated with several features of tumor aggressiveness, for
example, presence of ulceration (P < 0.001), higher tumor thickness (P < 0.001), and mitotic rate (P < 0.001), but not presence of regional or distant metastases. Moreover, high SMAD7
expression independently predicted unfavorable outcome: melanoma-specific survival
(hazard ratio = 3.16, P < 0.001) and recurrence-free survival (hazard ratio = 2.88, P < 0.001). Taken together, our results underline the importance of TGFβ signaling
in cancer and define SMAD7 as a marker of aggressive tumor behavior and adverse clinical
outcomes in melanoma patients.
Abbreviations
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Article info
Publication history
Published online: September 26, 2018
Accepted:
September 23,
2018
Received in revised form:
August 13,
2018
Received:
May 22,
2018
Identification
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© 2018 Elsevier Inc. All rights reserved.
