Abstract 3887: The association between expression of ALDH1, KI67 and grading system in breast adenocarcinoma

Abstract

Abstract Introduction: Many studies have shown that the ALDH1 and Ki67 markers can accurately identify different types of cells in the breast. ALDH1 has proven to be a biomarker of breast cancer stem-like cells, while Ki67 has considered a proliferative marker. However, although Ki67 has been correlated with breast cancer grading, little attention has been given to the relationship between ALDH1 and histological grading. On the other hand, although ALDH1 has been correlated with intrinsic molecular subtype of breast cancer, there is an absence of literature between Ki67 and breast cancer subtypes. Thus, the goals of this study are to address the relationship between ALDH, Ki67 and histological grading in breast cancer. Methods and Material: Immunohistochemistry staining (IHC) for ALDH1 was performed on tissue micro array (TMA) of 200 patient samples with different histological grades of breast cancer. Similarly, IHC was used to identify and assess the expression of Ki67 on TMA of 66 patient samples of various breast cancer subtypes (40 Luminal and 26 TNBC). Both biomarkers were compared to respective normal breast tissue using t-test statistical analysis. Results: results showed that 51/129 (39.5%) of cancerous breast tissues were ALDH1 positive. ALDH1 positivity differed significantly between different grades cancerous breast tissues and normal tissue (p=0.0007). In addition, a direct relationship exists between increasing grade and increasing ALDH1 positivity, with grade 3 having the highest frequency and intensity of ALDH1 positivity (p=0.005). In normal tissue, 6/25 (24%) cores on the tissue microarray showed presence of Ki67. The average percentage of cells containing in Ki67 positive cores for normal tissue was 2.54%. In luminal subtypes, 30/38 (78.9%) patients on the tissue microarray showed presence of Ki67. The average percentage of cells containing Ki67 in luminal breast cancer, for patients with Ki67 positive cores was 3.93%, with a median of 2.5%. Ki67 was also present in 24/26 (92.3%) patients with triple negative breast cancer. Among the 24 patients with Ki67 present, an average of 6.91% of cells exhibited Ki67 in each core, with a median of 4.25%. A one-tailed student's T-test was used to determine statistical significance of the difference in Ki67 expression (including the patients with no Ki67 expression) between Luminal and Triple Negative subtypes of breast cancer with a p-value of 0.026 Conclusion: Our findings suggest that higher grades of breast cancer may contain higher quantities of breast cancer stem like cells. Given the role of Ki67 in cell proliferation, the increased presence of Ki67 in triple negative breast cancer, when compared to Luminal subtypes of breast cancer, may suggest a correlation with a worse prognosis. Identification of Ki67 positivity in breast cancer cells may aid in the development of prognosis and novel treatment techniques. Citation Format: Yahya I. Elshimali, Pierre Tamer, Sami Dwabe, Yanyuan Wu, Marianna Sarkissyan, Jaydutt V. Vadgama. The association between expression of ALDH1, KI67 and grading system in breast adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3887. doi:10.1158/1538-7445.AM2014-3887