Can Histological Grade and Mitotic Index Replace Ki67 to Determine Luminal Breast Cancer Subtypes?

Abstract

<br /> <strong><span style="font-size: small;">Introduction: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Breast cancer can be classified into subtypes based on immunohistochemical markers, with Ki67 expression levels being used to divide luminal BC tumors in luminal A and B subtypes; however, Ki67 is not routinely determined due to a lack of standardization. </span></span><strong><span style="font-size: small;">Objective: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">To evaluate histological grade and Eliminate: the mitotic index </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">to determine if they can be used as an alternative method to Ki67 staining for luminal subtype definition. </span></span><strong><span style="font-size: small;">Methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">We evaluated estrogen receptor positive breast cancer tissue samples. Pathological analysis included determination </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">of Ki67. A low level of Ki67 was defined as <14% positive cells. </span></span><strong><span style="font-size: small;">Results: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">We evaluated 151 breast cancer samples; </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">24 (15,9%) were classified as I; 74 as HG II (49%), and 53 (35,1%) as HG III. The median value for Ki67 was 13% (range: <1% - 82%) and for MI was 2 (0-12). Histological grade I tumors exhibited Ki67 values significantly lower than HG II and III tumors (Anova, Tamhane test p=0,001). A higher Ki67 value was related to a higher MI (Rho Sperman p=0,336; R2= 0,0273). ROC curve analysis determined that a MI ≥ 3 had a sensibility of 61.9% and specificity of 66.7% in predicting a high Ki67 value (≥14%) (area under the curve: 0,691; p =0,0001). A HG I tumor or HG II-III with MI ≤2, had a high probability of corresponding to a LA tumor (76,3%), as defined using Ki67 expression, while the probability of a LB subtype was higher with HG II-III and a MI ≥3 (57.4%). Global discrimination was 68.1%. </span></span><strong><span style="font-size: small;">Conclusions: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">For the LA subtype, our predictive model showed a good correlation of HG and MI with the classification based on Ki67<14%. In the LB subtype, the model showed a weak correlation; therefore Ki67 determination seems to </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">be needed for this group of patients. </span></span>