Immunohistochemical expression of substance P in breast cancer and its association with prognostic parameters and Ki-67 index.

BACKGROUND: The neuropeptide substance P is a potential biomarker and therapeutic target in cancer. The main objectives of this study were to investigate the expression level of substance P in different breast cancer molecular subtypes and identify its association with clinicopathological parameters of patients and with Ki-67 index. METHODS: A retrospective analysis was performed for a total of 164 paraffin-embedded breast cancer tissue samples [42 Her2/neu-enriched, 40 luminal A, 42 luminal B (triple-positive) and 40 triple negative subtypes]. The tissue microarray slides containing specimens were used to determine the expression of substance p and Ki-67 by immunohistochemical staining. RESULTS: The mean age of the cohort was 51.35 years. Twenty two percent of cases had low substance P expression levels (TS ≤ 5), while 78% had high expression levels (TS > 5). A significant association was found between SP expression level and breast cancer molecular subtype (p = 0.002), TNM stage (p = 0.034), pN stage (p = 0.013), axillary lymph node metastasis (p = 0.004), ER and PR statuses (p<0.001) and history of DCIS (p = 0.009). The average percentage of Ki-67 expression was 27.05%. When analyzed as a continuous variable, significant differences were observed between the mean Ki-67 scores and molecular subtype (p = 0.001), grade (p = 0.003), pN stage (p = 0.007), axillary lymph node metastasis (p = 0.001), and ER and PR statuses (p <0.001). CONCLUSION: SP is overexpressed in most of the analyzed tissues and has a negative prognostic value in the breast cancer patients. Besides substance P is a potential therapeutic target in breast cancer.

Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability.

Intellectual disability is a heterogeneous disease with many genes and mutations influencing the phenotype. Consanguineous families constitute a rich resource for the identification of rare variants causing autosomal recessive disease, due to the effects of inbreeding. Here, we examine three consanguineous Arab families, recruited in a quest to identify novel genes/mutations. All the families had multiple offspring with non-specific intellectual disability. We identified homozygosity (autozygosity) intervals in those families through SNP genotyping and whole exome sequencing, with variants filtered using Ingenuity Variant Analysis (IVA) software. The families showed heterogeneity and novel mutations in three different genes known to be associated with intellectual disability. These mutations were not found in 514 ethnically matched control chromosomes. p.G410C in WWOX, p.H530Y in RARS2, and p.I69F in C10orf2 are novel changes that affect protein function and could give new insights into the development and function of the central nervous system.

Atorvastatin treatment modulates the interaction between leptin and adiponectin, and the clinical parameters in patients with type II diabetes.

The aim of this study was to examine the effect of atorvastatin treatment on levels of leptin, adiponectin and insulin resistance, and their correlation with clinical parameters, in patients with type II diabetes. Patients with diabetes (n=394) were divided into two groups, comprising 161 patients who received 20 mg/day atorvastatin (statin group), and 233 patients who did not receive statins (statin-free group). The results showed that atorvastatin treatment of patients with diabetes was not associated with changes in leptin, adiponectin, the leptin/adiponectin (L/A) ratio or homeostasis model assessment-insulin resistance (HOMA-IR). However, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and total cholesterol (Tchol) were positively correlated with leptin and L/A ratio in the statin group only (P<0.05). By contrast, high-density lipoprotein cholesterol (HDL-C) showed a significant positive correlation with adiponectin in the statin and statin-free groups (P<0.05). Additionally, a positive correlation was found between HOMA-IR and glycated hemoglobin (HbA1c), and TG, in both groups, whereas Tchol was positively correlated with HOMA-IR in the statin group only (P<0.05). When multivariate analysis was performed with HOMA-IR as the dependent variable, and with adjustment for age, body mass index (BMI) and waist circumference, HbA1c was found to be a significant predictor of HOMA-IR or insulin resistance. In conclusion, atorvastatin treatment may have several effects on the interaction between leptin and adiponectin, and on clinical parameters in patients with type II diabetes.