Abstract 2462: Rac and p-PAK expression among Puerto Rican breast cancer patients

Abstract

Abstract Breast cancer is the most common cancer among US women and is the second leading cause of death from cancer. Since metastasis is a major cause of death from breast cancer, we focused on Rac, a key metastasis driver regulating cancer cell migration and invasion. The direct downstream effector of Rac, p21-activated kinase (PAK), is auto-phosphorylated (in Thr 423) when activated by Rac to promote cancer metastasis. Accordingly, Rac and PAK expression is associated with higher stages and grades of multiple cancers and is also increased in breast ductal carcinoma and lymph node metastases. The breast cancer incidence in Puerto Rico (PR) is lower than that of the mainland US; however, mortality rates are higher due to increased invasion and metastasis. Therefore, the objective in this study was to determine Rac and phospho (p)-PAK expression in breast cancer tissues from Puerto Rican patients. Consecutive cases of formalin-fixed paraffin embedded infiltrating mammary carcinomas from core needle biopsy samples were obtained from the Auxilio Mutuo Hospital, San Juan, PR. Our initial study was limited to estrogen receptor (ER)/progesterone receptor (PR) positive (+) patients with variable human epidermal growth factor receptor (HER2) status. Of the 16 patients studied, 10 were HER2 negative and 6 were HER2 positive. Histologic tumor grade via Nottingham criteria was determined and immunohistochemical stains for ER, PR, HER2 protein and Ki-67 were performed, as well as HER2 in situ hybridization for final determination of HER2 status. To evaluate the expression of Rac1, we used immunofluorescence (IMFL) with specific antibodies. p-PAK status was evaluated via immunohistochemistry (IHC) with specific antibodies to p-Thr423-PAK. The IMFL and IHC scores were determined by analyzing the staining intensity graded as follows: 0, no staining; 1, weak staining; 2, moderate staining; 3, strong staining. There were no significant differences in Rac1 expression based on HER2, ER, or PR status or Tumor Grade. Since Rac1 is activated via upstream receptor signaling such as HER2, we determined p-PAK staining as a measure of Rac activity. p-PAK staining was detected in ductal carcinoma (DC) in situ and invasive DC, with stronger staining in cancer cells infiltrating the surrounding tissue. p-PAK levels were elevated in HER2 positive compared to HER2 negative breast tumor tissue, independent of ER or PR status. Based on this data, we posit that selective Rac activation in HER2 positive breast cancers contribute to enhanced cancer malignancy in Puerto Rican patients. This will be validated by a larger sample size of breast cancer tissue comparing HER2/ER/PR status and cancer grade from Puerto Rican (Hispanic) and Caucasian patients. Citation Format: Mariangeline I. Gonzalez Ortiz, Magaly Martinez-Ferrer, Victor P. Carlo, Suranganie Dharmawardhane. Rac and p-PAK expression among Puerto Rican breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2462.