Stem Cell Marker Kit Is an Independent Prognostic Marker for Pancreatic Endocrine Tumors A Novel Finding Derived from Analysis of Islet Cell Differentiation Markers
L Zhang, TC Smyrk, C Lohse, RV Lloyd. Mayo Clinic, Rochester, MN
Background: The biologic behavior of pancreatic endocrine tumors (PETs) is difficult to predict based only on histologic features. CK19 has been shown to be a reliable prognostic marker for PETs. The underlying mechanism explaining why CK19 positive PETs have worse prognosis is unknown. Recently, the differentiation of islet cells from stem cells has been studied extensively, and a few proteins have been shown to play key roles or to serve as markers in different stages of differentiation. Kit is a stem cell marker in a variety organs including pancreas. CK19 is the first cytokeratin expressed in differentiating cells. Pax6 is usually expressed in more mature cells. The aim of study was to stage tumors along the line of islet cell differentiation and to correlate with biological behavior of PET.
Design: One hundred and two patients surgically treated for PETs between 1987 and 2002 were identified. Immunostains were performed using following antibodies: Kit, CK19, and Pax6. Associations of immunohistochemical features with survival were evaluated using Cox proportional hazards regression models.
Results: Forty-three patients died of disease at a mean of 5.4 years. Overall survival rates at 5 and 10 years were 79.6% and 50.6%, respectively. The molecular markers Kit, CK19, and Pax6 were combined to test their ability to predict death as follows: Kit + tumors (n=22); Kit-/CK19+ tumors (n=38); Kit-/CK19-/Pax6+ tumors (n=35); and Kit-/CK19-/Pax6- tumors (n=6). The overall survival differed significantly among all four groups (p<0.001; see Figure).
Conclusions: We found that molecular markers can be used to determine the degree of PET differentiation. The stem cell marker Kit positive PETs have the most aggressive behavior because tumor cells are at a relatively primitive stage. Ck19 positive tumors with some degree of differentiation have somewhat better prognosis followed by Pax6 positive tumors with the best prognosis. By understanding the molecular pathway of islet cell differentiation, a new and strong predictive marker Kit was identified. A similar strategy may be applicable to other tumor types in order to define new prognostic markers.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 91, Monday Morning