title: Lgr5 over-expression is positively related to the tumor progression and HER2 expression in stage pTNM IV colorectal cancer.
abstract: Recent studies display that Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) appears to involve the initiation of colorectal cancer (CRC). However, its role in the progression of CRC is not clear at present. In the present study, the expression of Lgr5, HER2, VEGF, and Ki-67 was detected by immunohistochemistry in primary cancer tissue and the matched normal mucosa, metastatic lymph node and distant metastatic tissues in 42 CRC cases staged as pTNM IV. The correlation of Lgr5 over-expression with the CRC progression, survival time, and expression of HER2, VEGF, and Ki-67 was evaluated. Moreover, the Lgr5 expression at the invasive front or residual cancer cells around coagulation necrosis was compared with that at the center of CRC in 51 paraffin embedded tissues. The results revealed that Lgr5 over-expression was more frequently found in the metastatic tissues of both lymph nodes and distant area when compared with primary CRC tissue (P<0.05). Additionally, cancer cells in the invasive front and residual cancer cells around or among the coagulation necrosis presented stronger Lgr5 immunoreactivity than that at tumor center (P<0.05), and strong positive staining was often observed in tumor budding cells. While, HER2 over-expression was detected in 28.9% (IHC 3+) and 42.1% (IHC 3+/2+) of CRC patients, neither Lgr5 nor HER2 expression was significantly related to the prognosis of CRC patients, though there was a positive correlation between Lgr5 and HER2 (P<0.05) or Ki-67 expression (P<0.05). In conclusions, Lgr5 over-expression might involve the proliferation, invasion, and distant and regional metastasis of CRC cells, and has potential positive relation to HER2 expression.
authors.affiliation: Department of Emergency Medicine, The Affiliated Drum Tower Hospital, Nanjing University Medical School Nanjing 210008, Jiangsu Province, China.
authors.forename: Feng-Juan
authors.initials: FJ
authors.lastname: Gao
authors.affiliation: Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School Nanjing 210008, Jiangsu Province, China.
authors.forename: Jie-Yu
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School Nanjing 210008, Jiangsu Province, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Wu
authors.affiliation: Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School Nanjing 210008, Jiangsu Province, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School Nanjing 210008, Jiangsu Province, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School Nanjing 210008, Jiangsu Province, China.
authors.forename: Xiang-Shan
authors.initials: XS
authors.lastname: Fan
authors.affiliation: Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School Nanjing 210008, Jiangsu Province, China ; Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System and Harvard Medical School West Roxbury, Massachusetts 02132, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D043562:Receptors, G-Protein-Coupled; D042461:Vascular Endothelial Growth Factor A; C116884:LGR5 protein, human; C508053:ERBB2 protein, human
keywords: Colorectal cancer; HER2; Lgr5; prognosis; progression