Relation of epidermal growth factor receptor and estrogen receptor-independent pS2 protein to the malignant transformation of mucinous cystic neoplasms of the pancreas.

OBJECTIVE

To evaluate the role of epidermal growth factor receptor (EGF-R) and pS2 protein in the evolution of malignancy in mucinous cystic tumors of the pancreas.

BACKGROUND

Mucinous cystic tumors of the pancreas include histologically benign but premalignant mucinous cystic neoplasms and mucinous cystadenocarcinoma. The molecular events leading to transformation from a benign to a malignant mucinous tumor are not known. Overexpression of EGF-R and detection of an estrogen-induced protein (pS2) has been demonstrated in ductal adenocarcinomas of the pancreas, but these factors have not been evaluated in mucinous cystic tumors.

DESIGN

Twenty-six mucinous tumors were examined for EGF-R, pS2 protein, and estrogen and progesterone receptors.

RESULTS

Eight (61.2%) of 13 malignant tumors exhibited increased expression of EGF-R, whereas EGF-R was not detected in any of the 13 benign tumors (P = .002). The pS2 protein was detected in nine of 11 malignant and 11 of 11 benign tumors (P = .480). Estrogen and progesterone receptors were not detected in the epithelium of either tumor type. The median survival time of the patients with EGF-R-negative tumors was 29.0 months compared with 14.5 months for those with EGF-R-positive tumors, but this difference did not reach significance owing to the small population size.

CONCLUSIONS

Overexpression of EGF-R in mucinous cystic tumors, as in ductal adenocarcinomas, may be an important feature associated with malignancy and may have prognostic significance. Failure to detect EGF-R in histologically benign epithelium suggests that the upregulation of EGF-R may be important in the evolution of aggressive behavior. The expression of pS2 protein appears to be independent of estrogen and may play a role in the proliferative activity of mucinous tumors. However, pS2 expression is not a feature associated exclusively with malignancy.