Abstract. The premalignant potential of Peutz-Jeghers syndrome (PJS) hamartomas has not been established. The major gene responsible for PJS is LKB1. LKB1 has a complex cellular role, therefore, the exact role of LKB1 in PeutzJeghers syndrome hamartomas (PJSs) is particularly difficult to understand. It has recently been found that LKB1 functions in the Wnt pathway in Xenopus during early development. Aberrant ß-catenin expression, the key regulator of the activated Wnt/ß-catenin signaling pathway, appears to stimulate interferon-induced gene 1 (IFITM1) products in intestinal tumorigenesis. Both contribute to intestinal tumor formation and tumor progression. This study was designed to investigate expression of LKB1, ß-catenin and IFITM1 in PJSs, colorectal adenomas (CRAs), colorectal carcinomas (CRCs) and normal colorectal mucosas (NCs) using RT-PCR and immunohistochemistry. Immunofluorescence was used to assess the co-expression characteristics of ß-catenin and IFITM1. Results showed that the expression profiles of LKB1, ß-catenin and IFITM1 in PJSs were similar to those in CRAs both at the mRNA and protein levels. The cytoplasmic level of ß-catenin expression correlated strongly with LKB1 and IFITM1 expression in the tumor cells. The dyregulation of ß-catenin was found in a majority (16/20) of the PJS polyps. Immunofluorescence also revealed co-expression of ß-catenin and IFITM1 in the cytoplasm of the PJSs. These findings suggest that Wnt signaling may be activated in a subset of PJSs, and activation of the Wnt/ß-catenin signaling in PJS polyps may be caused by LKB1 expression. The activated ß-catenin signaling pathway including IFITM1 might play an important role in a subset of PJS polyps. IntroductionHamartomatous polyps arising in PJS patients are generally considered to lack premalignant potential although rare neoplastic changes in these polyps and an increased gastrointestinal cancer risk in PJS are well documented (1). The constellation of anomalies associated with PJS in humans such as gastrointestinal polyps and epithelial tumorigenesis points to a complex function for LKB1 in various cellular processes (2,3). It has been reported that no correlation exists between the LKB1 mutation and the incidence of cancer (4,5). Yet, several candidate genes are still under investigation which work alone or in concert with the LKB1 gene (6,7). Mechanisms underlying the development of hamartomas and carcinomas are still not fully elucidated (8).LKB1 has a complex cellular role. It was first identified as a tumor suppressor gene through its association with PJS. To date, the role of LKB1 in cancers is still unknown (9). It has been recently suggested that LKB1 is essential to protect cells from apoptosis under energy stress (10-12). LKB1 is involved in diverse signaling molecules, and studies of the Xenopus LKB1 homolog XEEK (Xenopus early embryonic kinase) support a model in which LKB1 cooperates with the Wnt pathway through its interaction with GSK-3ß (13). Constitutive activation of the Wnt pathway results in th...

Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder resulting from mutations in serine/threonine kinase 11 (STK11) and characterized by gastrointestinal (GI) hamartomatous polyps, mucocutaneous pigmentation, and an increased risk for specific cancers. Little is known about the genetic implications of specific STK11 mutations with regard to their role in dysplastic and malignant transformation of GI polyps. Peripheral blood genomic DNA samples from 116 Chinese PJS patients from 52 unrelated families were investigated for STK11 mutations. Genotype-phenotype correlations were investigated. The mutation detection rate was 67.3% (51.9% point mutations, 15.4% large deletions). Fourteen out of the 25 point mutations identified were novel. Nearly one-third of all mutations, 8/27 (29.6%), were in exon 7, the shortest out of the nine exons. Strikingly, mutations affecting protein kinase domain XI, encoded in part by exon 7, correlated with a 90% (9/10) incidence of GI polyp dysplasia. In contrast, only two out of 17 (11.8%) nondomain XI mutations were linked to polyp dysplasia (P = 0.0001). The extent of the association between dysplasia and the development of GI-related cancers is currently unknown but our results highlight a novel STK11 genotype-phenotype association as the basis for future genetic counseling and basic research studies.

Longitudinal parallel compression suture is a safe, easy, effective, practical, and conservative surgical technique to stop intractable PPH from the lower uterine segment, particularly in women who have a cesarean scar and placenta previa/accreta.