Relation of epidermal growth factor receptor and estrogen receptor-independent pS2 protein to the malignant transformation of mucinous cystic neoplasms of the pancreas
R. E. Kirby, K. B. Lewandrowski, J. F. Southern, C. C. Compton and A. L. Warshaw
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston.
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.
