The Effect Of New Test Guideline On The Interpretation Of HER2 And The Diagnostic Value Of E-cadherin Complex In The Invasive Breast Cancer

Global cancer statistics in 2018 show that breast cancer still ranks first in both morbidity and mortality in female,and HER2-positive breast cancer accounts for 25%to 30%of all breast cancers.This type of breast cancer progresses faster,has a higher degree of malignancy,is more prone to recurrence and metastasis,and has a poor prognosis.In recent years,a variety of HER2-targeted therapeutic drugs have been marketed and applied,and the treatment results showed that HER2-positive breast cancer patients can benefit significantly.Therefore,how to accurately detect the status of HER2 is of great importance for selecting the population with potential benefits from HER2-targeted therapy.E-cadherin.as an adhesion molecule that maintains the polarity and integrity of epithelial cells,is mostly manifested as the loss of E-cadherin protein in invasive lobular carcinoma,which is of great value in the routine pathological differential diagnosis of invasive lobular carcinoma and invasive ductal carcinoma.However,it has been found that some high grade invasive ductal carcinoma can also be manifested as the loss of E-cadherin protein,and there may be morphological overlap between invasive lobular carcinoma,especially pleomorphic lobular carcinoma,and high grade invasive ductal carcinoma,so the diagnosis of these cases is often challenging.On the one hand,this study aims at the point of accurate detection and interpretation of HER2 in the selection link of potential beneficiaries of HER2 targeted therapy that is currently of clinical concern,to explore the influence of 3 version ASCO/CAP HER2 test guidelines on HER2 results,and to explore the molecular characteristics of these increased HER2 equivocal cases under the ASCO/CAP 2013 guidelines.On the other hand,in view of the special cases of invasive ductal carcinoma and invasive lobular carcinoma that are still difficult to be diagnosed at present,we explored the expression pattern of E-cadherin complex immunophenotype in these special cases in order to provide research basis for the accurate diagnosis of these special cases.Section 1:Atotal of 1894 patient samples which were initially diagnosed as invasive ductal carcinoma and done the FISH testing from 2007 to 2013 in Cancer Hospital,Chinese Academy of Medical Sciences were analyzed for both immunohistochemistry(IHC)and fluorescence in situ hybridization(FISH).HER2 FISH amplification was examined and re-assessed using 2013 and 2018 guidelines.The results showed that comparing with ASCO/CAP 2007,the HER2 positive cases were increased from 38.5%to 40.2%and the equivocal cases were increased from 1.3%to 7.3%according to the ASCO/CAP 2013 guidelines(P<0.001).Compared with ASCO/CAP 2013,the equivocal cases were decreased from 7.3%to 0%and the negative cases were increased from 52.5%to 60.0%according to the ASCO/CAP 2018(P<0.001).These increased equivocal cases based on the ASCO/CAP 2013 exhibited similar clinicopathologic features with Luminal B type cases.Section 2:A total of 11805 cases which were initially diagnosed as invasive ductal carcinoma and invasive lobular carcinoma from 2010 to 2018 in Cancer Hospital,Chinese Academy of Medical Sciences were collected and sorted out.We collected and reviewed the HE slides and immunohistochemical slides(E-cadherin).There were a total 26 targeted cases selected for this study,including 13 cases which showed the morphology of invasive ductal carcinoma with the loss of E-cadherin protein,6 cases which showed the morphology of invasive lobular carcinoma with the expression of E-cadherin and 7 cases of pleomorphic lobular carcinoma.The results showed that among the 13 cases which showed the morphology of invasive ductal carcinoma with the loss of E-cadherin protein,9 cases showed the strong staining on cell membrane of p120-catenin and ?-catenin,and 4 cases showed the staining in cytoplasm of p120-catenin with negative staining of ?-catenin.Among the 6 cases which showed the morphology of invasive lobular carcinoma with the expression of E-cadherin protein,3 cases showed strong staining on cell membrane of E-cadherin,p120-catenin and ?-catenin,2cases showed the staining in the cytoplasm of all three,and 1 case presented the staining in the cytoplasm of E-cadherin with negative p120-catenin and ?-catenin.Among the 7 cases of pleomorphic lobular carcinoma,6 cases showed E-cadherin(-),p-catenin(-)with the staining in the cytoplasm of p120-catenin,and 1 case presented negative staining of all three.