HER3 protein expression in relation to HER2 positivity in patients with primary colorectal cancer: clinical relevance and prognostic value.
The clinical and prognostic significance of HER3 expression and its relation to HER2 status in primary colorectal cancer (pCRC) were investigated. We retrospectively analysed 365 consecutive cases of pCRC that had been previously evaluated for HER2 status and included their 143 matched lymph node metastases. Immunohistochemistry (IHC) was performed to assess HER3 expression using tissue array methods. Of 364 eligible patients, HER3 overexpression was detected in 251 cases (69 %) (IHC 2+, n = 186 and IHC 3+, n = 65). HER3 overexpression was inversely correlated with histologic grade (p = 0.006), tumour size (p < 0.001), tumour depth (p < 0.001), TNM stage (p = 0.002), lymphatic invasion (p = 0.004), lymph node metastasis (p = 0.013) and distant metastasis (p = 0.039). Moreover, it positively correlated with both HER2 overexpression (p = 0.007) and HER2 gene amplification (p = 0.006). Although HER3 overexpression was associated with longer survival in univariate analysis (p = 0.026), it was not an independent prognostic factor in multivariate analysis (p = 0.359). Moreover, co-alteration of HER3 and HER2 was associated with neither survival nor any clinicopathologic parameter except tumour location in the rectum. Although not an independent prognostic factor for overall survival, HER3 overexpression was associated with several favourable prognostic clinicopathologic parameters. Additionally, HER3 overexpression strongly correlated with HER2 positivity in this cohort of patients.
Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
An Na
AN
Seo
Yoonjin
Y
Kwak
Woo Ho
WH
Kim
Duck-Woo
DW
Kim
Sung-Bum
SB
Kang
Gheeyoung
G
Choe
Hye Seung
HS
Lee
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D020893:Receptor, ErbB-3 / Q000096:biosynthesis*; D012189:Retrospective Studies; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human