title: Aberrant expression of Sonic hedgehog signaling in Peutz-Jeghers syndrome.
abstract: The SHH signaling pathway is critical for gastrointestinal development and organic patterning, and dysregulation of SHH pathway molecules has been detected in multiple gastrointestinal neoplasms. This study investigated the role of the SHH signaling pathway in PJS. Expression of SHH, PTCH, and GLI1 was examined by real-time PCR and immunohistochemistry in 20 normal tissues and 75 colorectal lesions (25 PJPs, 25 adenomas, and 25 adenocarcinomas). Expression of SHH, PTCH, and GLI1 mRNA was higher in PJPs than in normal tissue (P < .05) and gradually increased along the PJP-adenoma-adenocarcinoma sequence (P < .05). Immunostaining indicated that SHH expression was present in 60% of PJPs, 72% of adenomas, and 84% of carcinomas, whereas 68% of PJPs, 72% of adenomas, and 88% of carcinomas exhibited cytoplasmic expression of PTCH. Moreover, high GLI1 expression was detected in 56% of PJPs, 64% of adenomas, and 80% of carcinomas; and high nuclear expression of GLI1 was observed in 8 adenomas with atypia and 15 carcinomas. Increased SHH, PTCH, and GLI1 protein correlated positively with tumor grade (P = .012, P = .003, and P = .007, respectively), tumor depth (P = .024, P = .007, and P = .01), and lymph node metastasis (P = .05, P = .015, and P = .005). This study identified aberrant expression of SHH pathway molecules in PJS, and the findings may supply a novel mechanism for the development of PJ polyps.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xu
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Department of Gastroenterology, 534th Hospital of Chinese People's Liberation Army, Luoyang, Henan 471000, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.affiliation: Division of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: baopingwu@yeah.net.
authors.forename: Baoping
authors.initials: B
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D053823:Hedgehog Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010580:Peutz-Jeghers Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D015854:Up-Regulation; D055815:Young Adult; D000071676:Zinc Finger Protein GLI1
chemical_list: D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1
keywords: Colorectal carcinoma; GLI family zinc finger 1; Patched receptor; Peutz-Jeghers syndrome; Sonic hedgehog