Loss of p27 Nuclear Expression in a Prognostically Favorable Subset of Well-Differentiated Pancreatic Endocrine Neoplasms

Decreased expression of p27 occurs in aggressive colon, breast, and prostate neoplasms; p27 loss often correlates with worsened prognosis. Paradoxical overexpression has been described in benign and malignant pancreatic endocrine neoplasms (PENs). To investigate prognostic usefulness of p27 expression in PENs, we immunolabeled 42 primary PENs, with or without metastases, for p27 and separated lesions using a nuclear labeling index (NLI) of 10%. Of the 42 lesions, 26 demonstrated a 10% or higher NLI and 16 an NLI less than 10%. Comparison of lymph node status revealed that 50% of primary PENs with a 10% or higher NLI (13/26) demonstrated lymph node metastases, whereas only 6% of lesions with an NLI of less than 10% (1/16) demonstrated lymph node metastases (P = .0067). We next examined 11 liver and 7 lymph node metastases for p27 immunolabeling to determine whether p27 also is paradoxically retained in lesions that have metastasized. All 18 lesions demonstrated an NLI of 10% or higher for p27. Expression of p27 protein therefore appears to be lost in a subset of well-differentiated PENs with indolent features but paradoxically retained in PENs associated with metastatic disease.