Sonic hedgehog relates to colorectal carcinogenesis.
OBJECTIVE
The activation of Hedgehog signaling, which is critical to normal mammalian gastrointestinal development, is implicated in the development of various tumors, including colorectal cancer. In the pancreas, a precursor lesion overexpresses the Sonic hedgehog (Shh) when compared with normal tissue and cancer. The present study was designed to investigate Shh related protein expression in hyperplastic polyps and the adenoma-carcinoma sequence in the colon and rectum.


METHODS
Seventeen hyperplastic polyps, 24 adenomas of the colon, 69 adenocarcinomas (31 well-differentiated, 38 moderately-differentiated), and 30 normal colon samples were used in the study. We checked the expression of Shh, both patched (Ptch) and smoothened (Smo), by immunohistochemistry and compared the expression rate of each group.


RESULTS
Almost all adenomas, 22 of 23 (96%), expressed Shh. In other groups, 4 of 17 hyperplastic polyps (24%), 7 of 31 well-differentiated adenocarcinomas (23%), 13 of 38 moderately-differentiated adenocarcinomas (34%) and none of the 30 normal samples expressed Shh. The rate of expression in Ptch and Smo gradually increased in accordance with tumor progression.


CONCLUSIONS
This result indicates that Shh-related carcinogenesis and Shh expression may be a trigger for the adenoma-carcinoma sequence. This study suggests a potential therapeutic target of hedgehog blockade in carcinogenesis.
Yoshikawa
Kozo
K
Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Tokushima, Japan.
Shimada
Mitsuo
M
Miyamoto
Hidenori
H
Higashijima
Jun
J
Miyatani
Tomohiko
T
Nishioka
Masanori
M
Kurita
Nobuhiro
N
Iwata
Takashi
T
Uehara
Hisanori
H
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D003111:Colonic Polyps / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry; D008875:Middle Aged; D015398:Signal Transduction
D053823:Hedgehog Proteins; C509239:SHH protein, human