title: HER2 status in colorectal cancer: its clinical significance and the relationship between HER2 gene amplification and expression.
abstract: This study aimed at determining the incidence and clinical implications of HER2 status in primary colorectal cancer (CRC). HER2 status was investigated in two retrospective cohorts of 365 consecutive CRC patients (cohort 1) and 174 advanced CRC patients with synchronous or metachronous distant metastasis (cohort 2). HER2 status was determined by performing dual-color silver in-situ hybridization (SISH), mRNA in-situ hybridization (ISH), and immunohistochemistry (IHC). The incidence of HER2 protein overexpression (IHC 2+/3+) was approximately 6% (22 of 365 in cohort 1; 10 of 174 in cohort 2). HER2 gene amplification was observed in 5.8% of the patients from cohort 1 and 6.3% of the patients from cohort 2. HER2 gene amplification was more frequently observed in CRCs located in the rectum than in the right and left colon (P = 0.013 in cohort 1; P = 0.009 in cohort 2). HER2 status, determined by IHC, ISH, and dual-color SISH, was not significantly associated with aggressive CRC behaviour or patients' prognosis in both the cohorts. Of the combined cohort with a total of 539 cases, the concordance rate was 95.5% between dual-color SISH and IHC detection methods. On excluding equivocally immunostained cases (IHC 2+), the concordance rate was 97.7%. HER2 mRNA overtranscription, detected by ISH, significantly correlated with protein overexpression and gene amplification (P<0.001). HER2 gene amplification was identified in a minority of CRC patients with high concordance rates between dual-color SISH and IHC detection methods. Although HER2 status did not predict patients' prognosis, our findings may serve as a basis for future studies on patient selection for HER2 targeted therapy.
authors.affiliation: Department of Pathology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: An Na
authors.initials: AN
authors.lastname: Seo
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoonjin
authors.initials: Y
authors.lastname: Kwak
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
authors.forename: Duck-Woo
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Kang
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
authors.forename: Gheeyoung
authors.initials: G
authors.lastname: Choe
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases