Loss of SMAD4 protein expression is associated with high tumor grade and poor prognosis in disseminated appendiceal mucinous neoplasms.

The distinction between low-grade and high-grade disseminated appendiceal mucinous neoplasms is of critical importance in assessing prognosis and guiding patient therapy. SMAD4 encodes a protein that is a central component of the TGFβ signal transduction pathway, and loss of SMAD4 expression has been associated with poor prognosis in carcinomas of the gastrointestinal tract. We reviewed the clinicopathologic and molecular features of 109 disseminated appendiceal mucinous neoplasms identified over an 8-year period at our institution in an attempt to: (1) correlate SMAD4 immunohistochemical expression with tumor grade; and (2) assess the prognostic significance of SMAD4 expression in predicting overall survival.