Pancreatic Endocrine Tumors: A Possible Interaction of Utrophin and p53 in Malignant Progression
TA Rege, V Nose. Brigham & Women's Hospital, Boston, MA
Background: Pancreatic endocrine tumors (PET) are rare tumors with unpredictable clinical behavior. No histologic features or immunohistochemical markers have reliably predicted malignant progression. The 2004 World Health Organization (WHO) classification uses size, angioinvasion, mitotic activity and Ki-67 proliferative index as prognostic criteria. Recently, cytokeratin 19 and KIT have been reported as prognostic markers. Deletion of long arm of chromosome 6 is a common aberration in tumors. The cytoskeletal protein utrophin encoded on 6q is frequently lost in malignant PET. Prior studies raised the possibility of an important role of utrophin in the malignant progression of PET. P53 is a known oncogene implicated in a variety of tumors. The purpose of this study was to analyze the expression of utrophin and p53 in PET in a series of known malignant cases and cases with an unknown malignant behavior for its possible role in malignant progression.
Design: Sixty cases of PET were identified from our pathology files. The mean age at presentation was 57.6 years (range 25 to 88); the M:F ratio was 1:1, and the mean size was 4.3 cm (0.6 to 14 cm). The clinical follow-up data were examined and tumors classified according with the 2004 WHO classification and then separated in two groups as known malignant cases and cases with an unknown malignant behavior. Histopathologic and immunohistochemical stains were evaluated and utrophin (MANCHO3 clone 8A4; Dr. G. Morris, University of Iowa), p53, Ki-67 expression were scored semiquantitatively as 1+ (<5%), 2+ (5-10%), 3+ (10-50%), and 4+ (>50%).
Results: Utrophin expression was present in malignant tumors and more frequently associated with p53 expression than with cases where p53 was negative. Utrophin and p53 expression was also associated with local invasion, size of tumor, and mitotic rate. WHO criteria, node metastases, mitotic count, and Ki-67 proliferative index, infiltrative border, necrosis, perineural invasion, extrapancreatic expression and tumor size were associated with poor prognosis.
Conclusions: We demonstrated that utrophin expression is associated with expression of p53 in known malignant PET. Our findings suggest a potential role for utrophin interaction with p53 overexpression in malignant progression and metastasis. Further studies are warranted to clarify the possible role in the malignant progression of PET, the regulation, and putative therapeutic applications of these proteins.
Monday, March 22, 2010 1:00 PM
Poster Session II # 87, Monday Afternoon