Establishment of an antibody specific for AMIGO2 improves immunohistochemical evaluation of liver metastases and clinical outcomes in patients with colorectal cancer

• Autori principali: Keisuke Goto (Autore), Mitsuhiko Osaki (Autore), Runa Izutsu (Autore), Hiroshi Tanaka (Autore), Ryo Sasaki (Autore), Akimitsu Tanio (Autore), Hiroyuki Satofuka (Autore), Yasuhiro Kazuki (Autore), Manabu Yamamoto (Autore), Hiroyuki Kugoh (Autore), Hisao Ito (Autore), Mitsuo Oshimura (Autore), Yoshiyuki Fujiwara (Autore), Futoshi Okada (Autore)
• Natura: Libro
• Pubblicazione: BMC, 2022-01-01T00:00:00Z.
• Soggetti: article
• Accesso online: Connect to this object online.
• Notes: 10.1186/s13000-021-01176-2; 1746-1596
• Keywords: AMIGO2; Monoclonal antibody; Colorectal cancer; Liver metastasis; Prognosis; Pathology; RB1-214
• Source: Diagnostic Pathology, Vol 17, Iss 1, Pp 1-12 (2022)

Abstract Instruction The human amphoterin-induced gene and open reading frame (AMIGO) was identified as a novel cell adhesion molecule of type I transmembrane protein. AMIGO2 is one of three members of the AMIGO family (AMIGO1, 2, and 3), and the similarity between them is approximately 40% at the amino acid level. We have previously shown that AMIGO2 functions as a driver of liver metastasis. Immunohistochemical analysis of AMIGO2 expression in colorectal cancer (CRC) using a commercially available anti-AMIGO2 mouse monoclonal antibody clone sc-373699 (sc mAb) correlated with liver metastasis and poor prognosis. However, the sc mAb was found to be cross-reactive with all three molecules in the AMIGO family. Methods We generated a rat monoclonal antibody clone rTNK1A0012 (rTNK mAb) for human AMIGO2. The rTNK mAb was used to re-evaluate the association between AMIGO2 expression and liver metastases/clinical outcomes using the same CRC tissue samples previously reported with sc mAb. Results Western blot analysis revealed that a rTNK mAb was identified as being specific for AMIGO2 protein and did not cross-react with AMIGO1 and AMIGO3. The rTNK mAb and sc mAb showed higher AMIGO2 expression, which correlates with a high frequency of liver metastases (65.3% and 47.5%, respectively), while multivariate analysis showed that AMIGO2 expression was an independent prognostic factor for liver metastases (p = 7.930E-10 and p = 1.707E-5). The Kaplan-Meier analyses showed that the rTNK mAb (p = 0.004), but not sc mAb (p = 0.107), predicted worse overall survival in patients with high AMIGO2 expression. The relationship between AMIGO2 expression and poor disease-specific survival showed a higher level of significance for rTNK mAb (p = 0.00004) compared to sc mAb (p = 0.001). Conclusions These results indicate that the developed rTNK1A0012 mAb is an antibody that specifically recognizes AMIGO2 by immunohistochemistry and can be a more reliable and applicable method for the diagnostic detection of liver metastases and worse prognosis in patients with high AMIGO2-expressing CRC.