A Novel Method to Characterize Invasive Ductal Carcinoma Tumor Biopsies Using Contact Angle Measurements

Purpose: The goal of this work is to develop a preclinical method to characterize human breast cancer biopsies of different racial origin. Contact angle measurements are used to assess the biopsies' surface properties and examine possible correlation with race/ethnicity, tumor type, and cancer grade. This method enables us to study differences in interaction of drugs directly in tumor tissues based on available covariate data of the obtained samples. Here, we present a study of 80 invasive ductal carcinoma tumor samples compared against their matching normal and/or cancer adjacent tissues. Methods: To obtain contact angles of tumor tissues, we developed a contact angle instrument capable of delivering a ~45 nL drop on top of a 1.5 mm biopsy using a modified goniometer with added custom components (DataPhysics Instruments USA Corp.). The system allows us to measure contact angles from 3 different positions (0°, -45°, 90°), and viewing the tumor tissue through an inverted microscope to determine drop position and quality. For this study, breast cancer tissues were obtained as tumor micro arrays (TMA) and as FFPE tissues with matching normal adjacent tissue. For TMA slides, two drops per tissue were delivered and the test was repeated with a subsequent section of the same TMA, unless the TMA included duplicate cores. For FFPE samples, tissues were processed with a microtome at a thickness of 15 µm, a minimum of 6 drops were delivered per tissue. Results: Aggregated data showed normal adjacent tissue (NAT) had an average contact angle (CA) of 51.4° ± 6.5° n=19, cancer adjacent tissue (CAT) had an average CA of 62.8° ± 8° n=59, grade 1 tumors had an average CA of 71.1° ± 7° n=13, grade 2 tumors had an average CA of 67.4 ± 9.1° n=49, and grade 3 tumors had an average CA of 64.6° ± 10.3° n=11. When comparing normal adjacent tissue against any other tissue, p-values ≤ 0.05 and power ≥ 0.80 were observed. When comparing cancer adjacent tissue, only CAT vs NAT and CAT vs grade 2 tumors had p-values ≤ 0.05 and power ≥ 0.80. Individually, 37 cases reached p-values ≤ 0.05 and power ≥ 0.80, were tumor tissue showed contact angles greater than their NAT or CAT. An additional 7 cases met p-values ≤ 0.05 and power ≥ 0.80, however, tumor contact angles were lower than their NAT or CAT. Finally, ignoring type 2 errors, then an additional 11 cases reached p-values ≤ 0.05. Conclusions: Higher contact angles of deionized water were observed in tumor tissues when compared to matching normal or cancer adjacent tissue. It is clear that breast cancer tumors exhibit surface energy differences from normal adjacent tissues, with cancer tissue being more hydrophobic compared to normal tissue. Future work includes the determination of contact angles of Doxil-like liposomes in these tumors and the determination of surface energy of the tissues.