Ki-67 labeling index in breast carcinoma: An immunohistochemical study with correlation to molecular subtypes

Abstract

22107 Background: Given the uncertain significance of Ki-67 labeling index (LI) in the published literature and new insight provided by expression profiling, we comprehensively examined 205 cases of consecutive breast carcinoma at our institution. Methods: The tumors were classified as follows: Luminal A (LUMA; ER score 200 or higher, HER2 negative), Triple Negative (TN; ER and PR H-score 10 or less, HER2 negative), ERBB2 (ER and PR H-score 10 or less, HER2 positive), Luminal A-HER2 Hybrid (LAHH; ER H-score 200 or higher, HER2 positive), Luminal Unclassified HER2 Positive (LUHP; ER H-score 11–199, HER2 positive), Luminal Unclassified HER2 Negative (LUHN; ER H-score 11–199, HER2 negative). Tissue microarrays (TMAs) were constructed. TMAs were stained with anti-Ki-67 antibody. Ki-67 LI was calculated using an image analysis system. Results: Of the 205 tumors, 113 (55%) were classified as LUMA, 32 (15%) as TN, 8 (4%) as ERBB2, 10 (5%) as LAHH, 34 (17%) as LUHN, and 8 (4%) as LUHP. Although some luminal A tumors showed increased Ki-67 LI (generally accompanied by high mitotic activity), the average Ki-67 LI was lowest in ductal-type LUMA (average LI of 15.8%) and other receptor positive and HER2 negative tumors. Ki-67 LI was highest for TN tumors with almost all tumors showing LI above 50%. The ERBB2 tumors showed an average LI of 27.8%. Ki-67 LI alone was sufficient in differentiating among LUMA, ERBB2 and TN molecular subclasses (p value <0.01). A higher Ki-67 LI predicted lymph node metastasis in non-triple negative tumors (p value = 0.018). Table shows the relationship between Ki-67 LI and lymph node status irrespective of tumor size and molecular classes. Conclusions: Ki- 67 LI is an important prognostic factor in breast carcinoma. There is correlation between Ki-67 LI and molecular classes; however, intra-class differences in proliferation activity of receptor positive tumors likely account for individual differences in prognosis and response to chemotherapeutic agents. Ki-67 LI and lymph node status (n = 171) LN Negative LN Positive Total LI: 1–10% 41 (71%) 17 (29%) 58 LI: 11–25% 36 (68%) 17 (32%) 53 LI: 26–50% 18 (49%) 19 (51%) 37 LI: 51% or more 19a (83%) 4 (17%) 23 a : Of these 19 cases, 14 were triple negative; LI: Labeling Index; LN: Lymph Node No significant financial relationships to disclose.