Aberrant activation of Sonic hedgehog signaling in chronic cholecystitis and gallbladder carcinoma.
Sonic hedgehog (Shh) signaling has been extensively studied and is implicated in various inflammatory diseases and malignant tumors. We summarized the clinicopathological features and performed immunohistochemistry assays to examine expression of Shh signaling proteins in 10 normal mucosa, 32 gallbladder carcinoma (GBC), and 95 chronic cholecystitis (CC) specimens. The CC specimens were classified into three groups according to degree of inflammation. Compared with normal mucosa, CC, and GBC specimens exhibited increased expression of Shh. The immunoreactive score of Shh in the GBC group was higher than that in the mild to moderate CC groups but lower than that in the severe CC group (P < .05). Expression of Patched (Ptch) and Gli1 gradually increased from non-malignant cholecystitis to malignant tumors. Compared with CC specimens, GBC specimens showed higher cytoplasmic and membranous expression for Ptch (P < .05). Gli1 staining showed cytoplasmic expression of Gli1 in both CC (60% for mild, 77% for moderate, and 84% for severe) and GBC specimens (97%). Nuclear expression of Gli1 was detected in 16% of severe CC specimens with moderate to poor atypical hyperplasia, and in 62.5% of GBC specimens. Shh expression strongly correlated with expression of Ptch and Gli1. Furthermore, patients with strongly positive Gli1 staining had significantly lower survival rates than those with weakly positive staining. Our data indicate that the Shh signaling pathway is aberrantly activated in CC and GBC, and altered Shh signaling may be involved in the course of development from CC to gallbladder carcinogenesis.
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Fang
F
Xie
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Xiaoping
X
Xu
Huizhou Medical Institute, Huizhou 516003, China.
Angao
A
Xu
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Cuiping
C
Liu
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Fenfen
F
Liang
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Minmin
M
Xue
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Huiqiao Building, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: bailan99@yeah.net.
Lan
L
Bai
D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002764:Cholecystitis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005704:Gallbladder / Q000378:metabolism* / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D015996:Survival Rate
D053823:Hedgehog Proteins
Chronic cholecystitis; Gallbladder carcinoma; Gli1; Ptch; Sonic hedgehog pathway