Significance Of Expression Of HER-2in Colorectal Cancer

【Objective】To evaluate the HER-2protein level by immunohistochemistry (IHC) and therelevance to the clinicopathological characteristics as well as prognosis of colorectalcancer patients.To verify the consistency between HER-2/neu protein by IHC and itsgene amplification by fluorescence in situ hybridization (FISH) in colorectal cancersamples.【Methods】1. Part1: HER-2overexpression was examined with semiquantitative standardizedIHC in878formalin-fixed paraffin-embedded colorectal cancer samples.100paracancer normal tissues were selected as control at random.2. Part2: FISH analysis was applied to all IHC2+and3+tumors samples.20IHC0cases and20IHC1+cases randomly selected as control，respectively.【Results】1. Part1: A total of102(11.3%) out of878patients were determined byimmunohistochemistry to have overexpressed HER-2.25（2.8%）were stronglypositive (3+) and77（8.8%） showed moderate staining (2+). HER-2overexpression was more frequent in0stage cases as well asⅠ/Ⅱstage cases thanⅢ/Ⅳstage cases（P<0.001）.There was no relationship between HER-2overexpression and gender, age, tumor site, size, depth of invasion, lymph nodemetastases, or distance metastases (P>0.05). Colorectal cancer patients withHER-2positive exhibited higher five year survival rate (77.7%vs61.4%) thanHER-2negative patients but there was no statistical significance. In general, therewas also no correlation between HER-2overexpression and survival time.2. Part2: By FISH analysis, it was shown that64.0%(16/25) of IHC3+had HER-2gene amplication. In contrast, only6.5%(5/77) of IHC2+cases, and none of thecases with IHC0/1+randomly selected showed HER2gene amplification.Relatively high consistency results were detected between IHC3+, IHC0/1+andFISH (64.0%and100.0%), however, there was an extremely low consistent resultbetween IHC2+and FISH (only6.5%). HER-2gene amplification was observed in21(21.0%) of102cases with HER-2positive colorectal cancer samples and in21(2.4%) of878colorectal cancer samples.There was also no relationshipbetween HER-2gene amplification and survival time.【Conclusions】1. There is HER-2overexpression and HER-2gene amplification in colorectalcancer.Except clinical stages, there is no correlation between HER-2overexpressionand other clinicopathological datas as well as survival time.HER-2overexpressiondon’t correlate with established prognostic indicators.2. Though HER-2strongly positive and gene amplification are concordance in somedegree, IHC3+and2+cases should be further detected by FISH to assess HER-2gene status in colorectal cancer. And patients with HER-2amplification also mightconstitute potential candidates for targeted therapy with humanized monoclonalantibodies, such as trastuzumab.