The evaluation of the distribution of CD133, CXCR1 and the tumor associated macrophages in different molecular subtypes of breast cancer

Breast cancer has different molecular subtypes, which determine the prognosis and response to the treatment. CD133 is a marker for cancer stem cells in tumor microenvironment with diagnostic/therapeutic importance. The tumor associated macrophages (TAMs) interact with the cancer stem cells through the CXCR1 receptor. In this study, we wanted to investigate the expression of these markers in patients with different molecular subtypes, in order to detect pathophysiological mechanisms and new molecular targets for the prospective targeted therapies. In this study we hypothesized a difference in expression of these antigens among different subtypes. We investigated expression of antigens in breast cancer patients with luminal A (LA), luminal B (LB), HER2 overexpressing (HER2OE), triple negative (TN) subtypes (n=70) and control patients (n=10) without cancer diagnosis. We applied indirect immunohistochemistry and evaluated immunostaining. CD133 expression was at the periphery and CXCR1 expression was at the central area of the tumor. The cytoplasmic CXCR1, CD133 expressions and nuclear CD133 expression, which is prominent in the TN subtype, were observed in patients. There was a statistically significant difference between the groups for CD133 (p=0.004), CXCR1 (p=0.002) H-Score values and M2 macrophages/whole TAM ratios (p=0.022). Between the CD133 and CXCR1 H-scores, there was a weak positive correlation (r=0.249, p=0.035). This study showed the compartment specific expression of the CD133 and CXCR1 antigens in neoplastic cells. The use of CD133 as a stem cell marker may be limited to TN subtype, due to its heterogeneous expression. © 2020, Histology and Histopathology. All rights reserved

Deciphering the Clinical Presentations in LMNA-related Lipodystrophy: Report of 115 Cases and a Systematic Review

Context: Lipodystrophy syndromes are a heterogeneous group of rare genetic or acquired disorders characterized by generalized or partial loss of adipose tissue. LMNA-related lipodystrophy syndromes are classified based on the severity and distribution of adipose tissue loss. Objective: We aimed to annotate all clinical and metabolic features of patients with lipodystrophy syndromes carrying pathogenic LMNA variants and assess potential genotype-phenotype relationships. Methods: We retrospectively reviewed and analyzed all our cases (n = 115) and all published cases (n = 379) curated from 94 studies in the literature. Results: The study included 494 patients. The most common variants in our study, R482Q and R482W, were associated with similar metabolic characteristics and complications though those with the R482W variant were younger (aged 33 [24] years vs 44 [25] years; P < .001), had an earlier diabetes diagnosis (aged 27 [18] vs 40 [17] years; P < .001) and had lower body mass index levels (24 [5] vs 25 [4]; P = .037). Dyslipidemia was the earliest biochemical evidence described in 83% of all patients at a median age of 26 (10) years, while diabetes was reported in 61% of cases. Among 39 patients with an episode of acute pancreatitis, the median age at acute pancreatitis diagnosis was 20 (17) years. Patients who were reported to have diabetes had 3.2 times, while those with hypertriglyceridemia had 12.0 times, the odds of having pancreatitis compared to those who did not. Conclusion: This study reports the largest number of patients with LMNA-related lipodystrophy syndromes to date. Our report helps to quantify the prevalence of the known and rare complications associated with different phenotypes and serves as a comprehensive catalog of all known cases