CCR5 Δ32 and CTLA-4 +49 A/G Gene Polymorphisms and Interferon-ß Treatment Response in Croatian and Slovenian Multiple Sclerosis Patients.

The aim of the present study was to investigate the impact of CCR5 Δ32 and CTLA-4 polymorphisms on the response to IFN-ß treatment in our cohort of MS patients from Croatia and Slovenia. Genomic DNA was obtained from 295 MS patients (230 female; 65 male) classified as responders (n = 173) and non-responders (n = 122) based on clinical criteria for treatment efficacy. Genotyping was performed via PCR/PCR-RFLP. No significant differences in the genotype/allele frequencies of CCR5Δ32 and CTLA-4 +49 A/G were detected between male responders and non-responders. A significantly higher prevalence (p = 0.039) of the CTLA-4 +49 AA genotype was found in female responders (42.1%) compared to non-responders (28.9%). Using multiple forward regression analysis, the CTLA-4 +49 AA genotype significantly predicted a positive response to IFN-ß therapy in females (p = 0.011) and contributed to 4.5% of response variability. Furthermore, the combined presence of the CCR5Δ32 wtwt/CTLA-4 +49 AA genotype significantly predicted a positive response to treatment in females (p = 0.025). The age at disease onset, pretreatment relapse rate, and baseline EDSS score were not reliable predictors of treatment response in MS patients. Our results indicate that the presence of the CCR5Δ32 polymorphism was not associated with the response to IFN-ß treatment, whereas the CTLA-4 +49 polymorphism showed a positive correlation with an optimal response in female patients.

The role of different lymph node staging systems in predicting prognosis and determining indications for postmastectomy radiotherapy in patients with T1-T2pN1 breast carcinoma.

PURPOSE: Based on the risk of locoregional recurrence (LRR), postmastectomy radiotherapy (PMRT) is recommended in T1-T2pN1 breast carcinoma (BC). We aimed to elucidate our institutional strategies underlying selection of these patients for PMRT. In the no-PMRT subset, we compared various lymph node (LN) staging systems' abilities to predict 5­year overall and locoregional-free survival (OS/LRFS). METHODS: We retrospectively enrolled 548 women with T1-T2pN1 BC undergoing mastectomy and axillary LN dissection. Depending on PMRT delivery, the participants were divided into the PMRT and no-PMRT groups. Predictors of OS/LRFS were calculated for the no-PMRT group only. Based on Cox regression modelling, the number of positive LNs (PLN), negative LNs (NLN), LN ratio (LNR), log odds of PLN (LODDS), and modified LNR (mLNR) were modelled, each respectively, with OS model covariates (age, grade III, lymphovascular invasion [LVI], tumor size, hormone receptor [HR] status) and LRFS model covariates (age, grade III, LVI). The C­statistic, Akaike information criterion, and likelihood ratio χ2 of the models were compared. RESULTS: Median follow-up was 60.5 (18-82), 61 (28-82), and 60 (18-80) months for the entire cohort, PMRT, and no-PMRT group, respectively. The PMRT and no-PMRT groups had comparable OS (p = 0.235). LRFS was better (p = 0.030) in the PMRT group comprising 105 subjects (19.16%) who were younger, more likely to have a higher-grade, HR-, HER2+ tumors, more PLNs, fewer NLNs, Ki-67 ≥ 20%, LVI, and extranodal extension (p ≤ 0.001). In the no-PMRT group, LNR-based OS/LRFS models exhibited superior prognostic performance. CONCLUSION: In early-stage BC patients undergoing mastectomies, LN dissections and no PMRT, we propose LNR-based multivariable models to predict OS/LRFS with superior accuracy.