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Volume 51 (12): 1665-1672, 2003
Copyright ©The Histochemical Society, Inc.
Correlation of Staining for LKB1 and COX-2 in Hamartomatous Polyps and Carcinomas from Patients with Peutz–Jeghers Syndrome
Departments of Epidemiology (CW,CIA,MS,LN,MLF) and Pathology (AR), University of Texas MD Anderson Cancer Center, Houston, Texas, and Department of Medicine (TJM), Milton S. Hershey Medical Center, Pennsylvania State University, Philadelphia, Pennsylvania
Correspondence to: Marsha L. Frazier, Dept. of Epidemiology, Unit 189, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. E-mail: mlfrazier{at}mail.mdanderson.org
Germline mutations of the LKB1 gene lead to Peutz–Jeghers syndrome (PJS), which is associated with a predisposition to gastrointestinal polyposis and cancer. In this study we tested for germline mutations of LKB1 in 11 patients with PJS from nine families and analyzed the expression patterns of the LKB1 and cyclo-oxgenase-2 (COX-2) proteins in 28 Peutz–Jeghers polyps (PJPs) and five carcinomas from these patients by immunohistochemical (IHC) analysis. In eight of those families we identified seven different mutations, which consisted of two splice site mutations, two nonsense mutations, one small in-frame deletion, one frame-shift mutation, and one silent mutation. Immunostaining revealed nuclear and cytoplasmic expression of LKB1 protein in 23 PJPs and five carcinomas, nuclear expression alone in one PJP, and loss of LKB1 protein expression in four PJPs, indicating a heterogeneous LKB1 expression pattern in PJPs. Overexpression of COX-2 was detected in 23 (82%) of 28 PJPs and in all carcinomas. Despite heterogeneity in staining of LKB1 among individuals and even among samples from the same individual, we found statistically significant correlations in staining of LKB1 relative to COX-2. These results suggest that COX-2 plays a role in tumorigenesis in PJS and may therefore be considered as a potential target for PJS chemoprevention. (J Histochem Cytochem 51:1665–1672, 2003)
Key Words: Peutz–Jeghers syndrome • LKB1 • COX-2 • germline mutation • immunohistochemistry
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