title: Expression of GLI1 correlates with expression of lymphangiogenesis proteins, vascular endothelial growth factor C and vascular endothelial growth factor receptor 3, in colorectal cancer.
abstract: Aberrant activation of the hedgehog (Hh) signaling pathway is associated with tumorigenesis in various tissues. In colorectal cancer (CRC), evidence for Hh activation is inconsistent, and the relationship between the Hh signaling pathway and lymphangiogenesis has not been studied. The  aim of this study was to determine the relationship between Hh signaling and lymphangiogenesis and the association of this relationship with lymph node metastasis in CRC. We investigated 189 patients who underwent curative surgical resection for CRC between 2002 and 2004 at Korea University  Guro Hospital. Paraffin-embedded specimens of colorectal adenocarcinoma and adjacent normal mucosa were evaluated. Immunohistochemical staining for Sonic hedgehog (Shh), Gli1, vascular endothelial growth factor C (VEGFC), and VEGF receptor 3 (VEGFR3) was performed for each specimen. Tumor  specimen showed significantly strong staining of Shh, Gli1, VEGFC, and VEGFR3 compared with a normal specimen. Shh expression was not associated with Gli1 expression. Gli1 expression correlated positively with VEGFC and VEGFR3 expression (P < 0.05 in both) but not with lymph node  metastasis. Activation of the Hh signaling pathway associated with Gli1 promotes expression of lymphangiogenesis proteins, VEGFC and VEGFR3, in CRC. Further studies are necessary to determine the association of this relationship with lymph node metastasis in CRC.
authors: Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea.
authors: Kwang Dae
authors: KD
authors: Hong
authors: Youngseok
authors: Y
authors: Lee
authors: Baek-Hui
authors: BH
authors: Kim
authors: Sun Il
authors: SI
authors: Lee
authors: Hong Young
authors: HY
authors: Moon
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C509239:SHH protein, human; D014157:Transcription Factors; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; D000071676:Zinc Finger Protein GLI1; D040321:Vascular Endothelial Growth Factor Receptor-3