A Study Of Pathological Features And The Expression Of BRCA1,WWOX In Young Female Patients With Breast Carcinoma

【Objective】A retrospective study of the clinicopathological datas between young (≤35 years old) and elder(≥60 years old) female with breast carcinoma was made. The different points in pathological type,tumor size,histological grade,pathological staging,lymph node metastasis and other clinicopathological features were compared. The expressions of WWOX,BRCA1,ki67 were investigated in invasive ductal carcinoma(IDC) in young and elder groups.The mutations of BRCA1 exon 2 and 20 were analyzed in young female breast carcinomas.The aim was to explore the clinicopathological characteristics and biological markers in young female breast carcinomas.It maybe provide the basis for the early diagnosis and the reasonable treatment.【Methods】One hundred and eighty-one cases of breast carcinoma in young(≤35 years old) female were collected,diagnosed in Dept.of Pathology Qilu Hospital during January 1998 to December 2007.The age ranged from 19 to 35 years old with median age of 27.We also randomly selected 186 cases of breast carcinoma of elder(≥60 years old) female,confirmed by pathology during the same period.The age ranged from 60 to 85 years old with median age of 73.According to the diagnostic criteria of breast tumors of WHO in 2003,the pathological diagnosis and histological grades were made. And staging criteria(PTNM) of UICC in 2006 were employed to stage all of the cancer cases.Using immunohistochemistry method,the expressions of ER,PR,C-erbB2, Ki67,BRCA1 and WWOX were performed in tissue microarray of 219 cases of invasive ductal carcinoma which were devided into two groups,the young group(107 cases) and the elder group(112 cases).In addition,10 cases of fresh tissue samples of invasive ductal carcinoma were collected from the young(≤35 years old) female to detect the exon 2 and 20 of BRCA1 gene mutations using PCR amplification and direct sequencing method.All the datas were analyzed by SPSS 16.0 softwere for windows.【Results】There were total 2,537 cases of breast carcinoma diagnosed in Qilu Hospital of Shandong University,181 cases under 35 years old(7.1%).Among these 181 cases,there were 7 cases(3.9%) less than 25 years old,48 cases(26.5%) whose ages were between 26 to 30 and 126 cases(69.6%) whose ages were between 31 to 35. There were 488 cases whose ages were more than 60 years old(19.2%).Among these cases,321 cases(65.8%) were between 60 and 69 years old and 145 cases(29.7%) were between 70 and 79 years old.And other 22 cases were older than 80 years old (4.5%).Although the number of breast carcinoma cases increased obviously during the last ten years,there were no significant changes in young female.The slight increase was observed in the number of breast carcinoma cases in elder female every year.The invasive ductal carcinoma was the major histological type in both young and elder group,with the proportions of 77.3%and 84.4%respectively.The case number of tumors designed as T3 in diameter in the young group was significantly more than that in the elder group(P＜0.05).The case number of tumors designed as PTNM stagesⅢand in gradeⅢwere significantly much more in young group than that in the elder(P＜0.01).Compared with the elder group,the young group had higher metastasis rate of the axillary lymph node and the number of positive lymph nodes(P＜0.01).The results of immunohistochemistry showed that the positive rates of the expression of ER, PR,C-erbB2,BRCA1,WWOX and the high rate of Ki67 proliferation of the invasive ductal carcinoma in the young group were 66.4%(71/107),54.2%(58/107),27.1% (29/107),65.4%(70/107),86.9%(93/107) and 59.8%(64/107),respectively,while that in the elder group were 72.3%(81/112),40.2%(45/112),17.0%(19/112),35.7% (40/112),86.6%(97/112) and 55.4%(52/112),respectively.There was significant difference(P＜0.01) between the two groups in the expression of BRCA1 protein.The statistical results showed that the positive rate of the BRCA1 protein in young group was higher than that in the elder.The expressions of ER,PR,C-erbB2 and WWOX protein and Ki67 proliferation between the two groups were no significant difference (P＞0.05).Pearson correlation analysis showed that the parameters,BRCA1 was positively correlated with PTNM phases(r=0.158,P＜0.05) and axillary lymph node metastasis(r=0.202,P＜0.01).The tumor grade and the expressions of ER,PR, C-erbB2,WWOX and Ki67 proliferation had no significant relationships with the BRCA1(P＞0.05).The expression of WWOX had no correlation with the clinical indicators(P＞0.05).No mutation was detected in exon 2 and 20 of BRCA1 gene.【Conclusions】1.The number of cases of female breast carcinoma diagnosed in our hospital is obviously increased in the last ten years.There is no significant change in the number of cases of breast carcinoma in young female,whereas the cases of elder female slightly increased every year.2.Compared with the elder group,the breast cancer of the young patients are more likely to present larger tumor size,higher histological grade,higher PTNM staging and apt to the axillary lymph node metastasis.3.The expression rate of BRCA1 protein in the young group is higher than that in the elder group.The expression of BRCA1 is positively correlated with PTNM stages and axillary lymph node metastasis.4.No relationship is found between the expression of WWOX and the clinicopathological factors.5.In this study,the BRCA1 gene mutation is not detected in exon 2 and 20.We consider it maybe relate to the less number of the sample.To further clarify the BRCA1 gene mutation and its relationship with breast cancer in young female,we must expand the numbers of cases and increase testing sites in order to enhance its detection rate and make a definite conclusion.6.This study shows that the tumors are more malignant in the young breast cancer patients.The early diagnosis and reasonable therapeutic regimens are very important.