Can histological grade and mitotic index replace Ki67 to determine luminal breast cancer subtypes?

David Oddó, Dahiana Pulgar, Nicole Elgueta, Francisco Acevedo, Dravna Razmiliz, María Elena Navarro, Mauricio Camus, Tomás Merino, Ignacio Retamal, Alejandra Pérez-Sepúlveda, Alejandra Villarroel, Héctor Galindo, José Peña, César Sánchez*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Introduction: 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. Objective: To evaluate histological grade and Eliminate: the mitotic index to determine if they can be used as an alternative method to Ki67 staining for luminal subtype definition. Methods: We evaluated estrogen receptor positive breast cancer tissue samples. Pathological analysis included determination of Ki67. A low level of Ki67 was defined as < 14% positive cells. Results: We evaluated 151 breast cancer samples; 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%. Conclusions: 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 be needed for this group of patients.

Keywords

  • Breast neoplasms
  • Histology
  • Ki67 antigen
  • Mitotic index

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