The Stability Analysis Of Expression Of ER Protein In Primary Advanced Invasive Ductal Carcinoma

PurposeBreast cancer is the worst harmful disease of women's health,which lists head of women's malignant tumors,with rapid uptrend of incidence.As a hormone-dependent tumor,endocrine therapy is a conventional method for the treatment of breast cancer.Accurate assessment of estrogen receptor(ER)protein expression in breast cancer is critical for the development of clinical treatment and prognosis.Guidelines for the treatment of breast cancer indicate that ER protein expression status testing,together with PR,Ki67 index and HER-2 testing,should be included in the routine screening of invasive breast cancer.In this study,we compared the status of ER protein expression between primary lesions of breast invasive ductal carcinoma and their paired synchronous axillary lymph node metastases,analyzed the heterogeneity and stability of ER protein in the progression of lymph node metastases,with the aim to make better understanding of ER expression(especially ER expression in metastases)in breast cancer.Materials and Methods100 cases of paraffin blocks from women primary breast invasive ductal carcinoma with synchronous axillary lymph node metastases were collected from department of pathology in shaoxing People's Hospital with complete clinical data from 2008-2014 years for retrospective study.All patients went on the operation of modified radical mastectomy without any preoperative radiotherapy and chemotherapy for tumor treatment.ER protein expression was evaluated by IHC using total information TMA-based techniques on cores from five typical sites of primary tumor and all microscopically visible metastases sites of synchronous axillary lymph node in each case and the difference of ER protein expression among the cores were analyzed.Semi quantitative interpretation according to the number and intensity of ER stained tumor cells:ER(0):no staining cancer cell or<10%of invasive cancer cells presented weak nuclear staining;(1 +):10%-30%of invasive cancer cells presented little strong intensity nuclear staining;(2+):>30%of invasive cancer cells presented moderate strong intensity nuclear staining;(3+):>50%of invasive cancer cells presented strong intensity nuclear staining.ResultsFrom 100 primary lesions of invasive ductal carcinoma,500 tissue cores were punched out from the representative areas of the donor blocks,tumor cells were found in 472 cores(effective sites).As long as positive ER expression was found in any of 5 sites primary lesions,the case was defined as ER positive.The positive rate for ER expression in primary tumor was 53%.The details of ER expression as follows:in 47 cases,all the 222 effective primary sites were ER negative expression;in 41 cases,all the 192 effective primary sites were diffuse ER consistent expression scored as 3+;The other 12 cases with a total of 58 valid sites showed inconsistent intensity of ER expression.The sites of ER 3+,2+,1?,0 expression were 26(44.8%),13(22.4%),7(12.1%)and 12(20.7%),respectively.There were 626 effective sites of axillary lymph node metastases from 100 invasive ductal carcinoma cases.As long as positive ER expression was seen in any site from the nodes,the case was defined as ER positive in the axillary lymph node metastases.The positive rate for ER expression in axillary lymph node metastases was 54%.The details of ER expression as follows:in 46 cases,all the 249 effective axillary lymph node metastases were ER negative expression;in 33 cases,all the 177 effective axillary lymph node metastases were diffuse ER consistent expression scored as 3+;the other 21 cases with a total of 200 valid sites showed inconsistent intensity of ER expression.The sites of ER 3+,2+,1+,0 expression were 77(38.5%),15(7.5%),9(4.5%)and 99(49.5%),respectively.By comparing the status of ER expression between breast invasive ductal carcinoma primary lesions and their paired synchronous axillary lymph node metastases,in the 41 cases with ER positive 3+ expression in all sites of primary lesion,86.0%(234/272)of the lymph node metastases showed ER positive 3+ expression,3.7%(10/272),1.5%(4/272),and 8.8%(24/272)of the nodes scored as ER 2+,1+ and 0 expression,respectively.ER positive expression was seen in 39 of the 41 cases,for the other 2 cases,all the lymph node metastases were ER negative expression.For the 47 cases of ER negative expression in all sites of primary lesions,ER negative expression were seen in 96.1%(298/310)of the lymph node metastases,while ER positive sites of ER 1+,2+,3+ were seen in 3(1%),3(1%)and 6(1.9%)of the metastases nodes,respectively.Negative ER expressin in all the lymph node metastases was seen in 40 of the 47 cases.One case showed ER diffuse consistent positive 3+expression in all the metastatic nodes.In the remaining 6 cases,90.2%(74/82)nodes presented negative ER expression,the nodes of lymph node metastases scored as ER 1+,2+and 3+were 3.7%(3/82),3.7%(3/82)and 2.4%(2/82),respectively.There were overall 44 axillary lymph node metastases from 12 cases of ER inconsistent expression in primary lesions.Among them,4 cases showed negative ER expression in all the metastastic nodes,in another 4 cases,all nodes displayed diffuse consistent expression of 3+.In the remaining 4 cases,the metastatic nodes to be ER expression 3+,2+,1H+and 0 were 52.9%(9/17),11.8%(2/17),11.8%(2/17),and 23.5%(4/17),respectively.Overall concordance rate of ER protein positive expression between primary tumors and synchronous axillary lymph node metastases was 87%.By stratified analysis,from 53 cases with positive expression of ER in primary tumors,47 cases showed ER positive expression in the corresponding lymph node metastases,the concordance rate was 88.7%.In the 41 cases of ER positive 3+ expression in all sites of primary lesions,39 cases showed positive expression in the corresponding lymph node metastases,and the concordance rate 95.1%.From 47 cases of ER negative expression in all sites of primary lesions,40 cases showed negative expression in the corresponding lymph node metastases,with a concordance rate of 85.7%.From 12 cases of ER inconsistent(3+,2+,1+)expression in primary lesion,ER positive expression in lymph node metastases were seen in 8 cases,with the concordance rate 66.7%.Conclusions1.The concordance of ER protein expression between primary tumor and the synchronous axillary lymph node metastases was high,especially in the cases of negative expression or diffuse consistent expression of 3+ in all sites of primary tumors.2.Multi-site sampling both from primary lesion and its corresponding axillary lymph node metastases using TMA-based techniques can reflect more comprehensive information for ER status comparing to the conventional method.3.Identical ER positive 3+ or negative expression is the most common ER expression pattern for breast cancer.4.The positive rate of ER expression in this study was little lower,may be related to the selection of patients with lymph node metastases.