Clinicopathologic Features Of Basal-like Breast Cancer And Preliminary Study On Its Molecular Mechanism

Purpose Basal-like breast cancer is one of the subtypes of the molecular typing of the breast cancer which attracted a wide spread attention.They need treatment strategies different from other breast cancers based on their special molecular phenotype,so the identification becomes an important point.However,no uniform diagnostic criterium for basal-like breast cancers is available to date,the clinicopathologic and immunohistochemical features of them need more investigation,and conflicting results on its prognostic significance still remains.On the other hand,most information about basal-like tumors is based on the studies of western populations,except few reports based on Korean and Japanese.Little is known about that of Chinese population.So,using tissue microarray,immunohistochemistry,in situ hybridization and methylation-specific PCR techniques,we analyzed a large group of invasive breast cancers aimed at describing the clinicopathologic, immunohistochemical and prognostic features of basal-like breast cancers in Chinese population,and analyzing the diagnostic value of morphology and the effect of different diagnostic criteria on the prognostic analysis. Methods Immunohistochemistry was used to detect the expression of ER,HER2,CK5/6,EGFR,PR,CK14 on tissue microarray with 1452 invasive breast cancers.Based on the results,we categorized these cases into basal-like,HER2-overexpressing,luminal A,luminal B and null subtypes.Clinicopathological,morphological parameters and survival were compared between groups.Then we classified these invasive breast cancers according 4 different immunohistochemical criteria,and their prognostic significance was compared.The prognostic significance was analyzed on a small subgroup which expressed both basal markers and HER2,too.Finaly,we detected the expression of p53,p63,vim,cyclin D1,p16^INK4a,p21^WAF1,PTEN,BRCA1 immunohistochemically,and the mRNA and the promoter methylation of PTEN were detected too.Results Basal-like breast cancers constituted 17.0%of 1311 invasive breast cancers,showed significantly,bigger size,more frequent recurrence,infrequent node metastasis and higher grade.Morphologically, they are more prone to display diffuse growth pattern,central scar, pushing margin,lymphocyte infiltration,and squamous or spindle cell metaplasia.The disease-free survival and overall survival of basal-like breast cancers are significantly poorer than that of luminal A subtype., but the basal markers were not independent prognostic factor.With Nielsen and Triple-negative classification,basal-like breast cancers had poorer 5-year disease-free and overall survival than luminal A subtype. With Kim classification,only 5-year disease-free survival was poorer than luminal A subtype.With Basal-CK classification,no significant difference was found between basal-like and non-basal-like breast cancers.No difference was found between basal-like and the other ER-negative breast cancers under all the 4 classifications.However,a small group of breast cancers,which expressed not only basal markers but also HER2,displayed a significant poorer 5-year disease-free survival and 5-year overall survival than all the other subtypes of breast cancers. Different from all the other subtypes,basal-like breast cancers showed significant higher expression of pl6,Vim and p63,and the expression of p53 in basal-like tumors was higher than all the other subtypes except HER2-overexpressing subtype.Meanwhile,like the other ER-negative subtypes,basal-like breast cancers expressed lower level of cyclin D1, PTEN,p21^WAF1,BRCA1 protein and lower lever of PTEN mRNA than ER-positive breast cancers.The mRNA level of PTEN was associated with its protein level.No significant difference of PTEN promoter methylation was found between subtypes.Conclusions Basal-like breast cancers have distinct clinicopathologic features,and its prevalence in Chinese population is similar to that of western populations.Although not specific characteristics,the morphological clues can educe a correct diagnosis when combined with immunohistochemistry.Basal-like tumors have distinct immunohistochemical features,some of them different from all the other subtypes,and some of them similar to the other ER-negative subtypes and different from ER-positive subtypes.The results of prognostic analysis are variable when different criteria used for the diagnosis of basal-like tumors,so a uniform diagnostic criteria is essential for the further study of basal-like breast cancers.Moreover,basal markers are not the independent prognostic factor of breast cancers,basal-HER2 phenotype has the worst outcome compared with other breast cancers.