Jinghong Guan

Background: To investigate the role of tissue dielectric constant (TDC) in the detection and assessment of breast cancer-related lymphedema (BCRL) and to determine whether the TDC could potentially be used as a complementary method for arm volume measurement. Methods: Sixty-nine patients with BCRL were enrolled in this study. Local tissue water was assessed bilaterally by using the TDC method in four sites: upper arm, forearm, hand, and lateral thorax. Arm circumferences were measured at the 4-cm interval, starting from the shoulder to the wrist by using a tape measure. The arm volume was calculated by a standard formula. Patients' demographic information and clinical characteristics were also recorded. Results: Fifty-one of the 69 patients were diagnosed with clinical lymphedema. Using a TDC ratio of 1.2 or a diagnostic reference standard of ≥2 cm arm circumference, the sensitivity of these two methods was found to be identical at 73.9%. The TDC values in four sites on the affected side were significantly higher ( p < 0.05) relative to the unaffected side. The inter-side TDC ratio of upper arm and forearm was substantially higher than that of lateral thorax and hand ( p < 0.05). The TDC ratio of upper arm, forearm, and hand, especially of the upper arm and forearm, was positively correlated with inter-limb volume difference and stage of lymphedema. Conclusion: The TDC method elucidated a meaningful clinical correlation to the arm volume measurement. Applying those two methods together showed promise in the detection and assessment of BCRL. The forearm and upper arm were reliable examination sites for TDC measurements in the clinic.

The specific mechanism underlying the contribution of the Aldehyde dehydrogenase 1 (ALDH1) phenotype to metastatic behavior and early tumor relapse in breast cancer is currently unclear. 147 randomly selected invasive ductal carcinoma samples were assayed for expression of ALDH1A1, NOTCH1, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), and association of the ALDH1A1 phenotype with clinic pathological features was further evaluated. ALDH1A1-positive cells were detected in 63.3% (93 of 147) of tumors. 80.0% (32 of 40) of tumors with strong ALDH1A1 staining displayed early recurrence, compared with 20.0% (8 of 40) of tumors negative for ALDH1A1 expression (P = 0.027). ALDH1A1 status was significantly correlated with strong malignant proliferative marker Ki67 staining (P = 0.001), and no significantly different expression of ALDH1A1 across the subtypes of ER, PR, and HER2 expression and triple negative features of tumor tissue. Multivariate regression analysis demonstrated that elevated ALDH1A1 expression is an independent predictor of recurrence-free survival and distant metastasis-free survival. Notably, breast cancer tissue strong for ALDH1A1 expression displayed weak NOTCH1 staining compared to ALDH1A1 weak tumor tissue (P = 0.002), and the relationship between ALDH1A1 and NOTCH1 mRNA positivity was significant (Pearson correlation - 0.337, P = 0.014; Spearman’s rho - 0.376, P = 0.006). Elevated NOTCH1 mRNA level (using a cut-off value based on the median ALDH1A1 2^{-△△C T} value) was associated with reduction of ALDH1A1 mRNA level (P = 0.001). The ALDH1A1 phenotype is an independent predictor of early tumor relapse characteristic (specifically, incidence of early local recurrence and distant metastasis) of invasive ductal carcinoma. The NOTCH1 signaling pathway is possibly involved in the negative association of the ALDH1A1 phenotype with early malignant relapse in invasive ductal carcinoma.