Gene expression of PMP22 is an independent prognostic factor for disease-free and overall survival in breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Gene expression of peripheral myelin protein 22 (<it>PMP22</it>) and the epithelial membrane proteins (<it>EMPs</it>) was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study. We want to evaluate the prognostic impact of the expression of these genes on breast cancer.</p> <p>Methods</p> <p>In a retrospective multicenter study, gene expression of <it>PMP22 </it>and the <it>EMPs </it>was measured in 249 primary breast tumors by real-time PCR. Results were statistically analyzed together with clinical data.</p> <p>Results</p> <p>In univariable Cox regression analyses PMP22 and the EMPs were not associated with disease-free survival or tumor-related mortality. However, multivariable Cox regression revealed that patients with higher than median <it>PMP22 </it>gene expression have a 3.47 times higher risk to die of cancer compared to patients with equal values on clinical covariables but lower <it>PMP22 </it>expression. They also have a 1.77 times higher risk to relapse than those with lower <it>PMP22 </it>expression. The proportion of explained variation in overall survival due to <it>PMP22 </it>gene expression was 6.5% and thus PMP22 contributes equally to prognosis of overall survival as nodal status and estrogen receptor status. Cross validation demonstrates that 5-years survival rates can be refined by incorporating <it>PMP22 </it>into the prediction model.</p> <p>Conclusions</p> <p><it>PMP22 </it>gene expression is a novel independent prognostic factor for disease-free survival and overall survival for breast cancer patients. Including it into a model with established prognostic factors will increase the accuracy of prognosis.</p

The Prognostic Value of the Fibrinogen-Albumin-Ratio Index (FARI) in Patients with Advanced Vulvar Cancer

The present study aims to evaluate the pretherapeutic Fibrinogen-Albumin-Ratio Index (FARI), as currently reliable biomarkers to predict therapy response and prognosis of patients with advanced vulvar cancer are missing. Data of 124 consecutive patients, who underwent primary resection for vulvar cancer &ge; pT1b, were retrospectively analyzed. Associations between the FARI and disease recurrence were assessed fitting receiver operating characteristics (ROC) and binary logistic regression models; univariate and multivariable Cox regression models for disease-specific survival (DSS) and progression-free survival (PFS) were performed. A pretherapeutic low FARI cut at its median (&lt;9.67) is significantly associated with younger age (65.5 vs. 74.0 years) and higher risk of recurrence (52.4% vs. 26.2%). The ROC analysis calculates the area under the curve (AUC) of the FARI for a PFS &lt; 6 months of 0.700 and for a DSS &lt; 12 months of 0.706, outperforming fibrinogen and albumin alone. The FARI remained independently predictive for PFS (HR 0.84, 95% CI [0.99&ndash;1.03], p = 0.009) and DSS (HR 0.82, 95% CI [0.70&ndash;0.99], p = 0.019), also in multivariable survival analysis. Despite the FARI&rsquo;s promising predictive and prognostic value, however, further elucidation of its precise mode of action is warranted before clinical application as it appears to rely only on subtle changes of fibrinogen levels

Overweight as a Favorable Clinical Biomarker for Checkpoint Inhibitor Therapy Response in Recurrent Gynecologic Cancer Patients

Despite increasing clinical interest in adapting checkpoint inhibitor (CPI) therapies for patients with gynecologic malignancies, no accurate clinical biomarkers to predict therapy response and prognosis are currently available. Therefore, we aimed to assess the predictive and prognostic value of pretherapeutic body mass index (BMI) for recurrent gynecologic cancer patients as previously validated for other solid tumors. We evaluated patients with programmed cell death ligand 1 (PD-L1) positive and, in endometrial cancer, also mismatch repair deficient (MMR) gynecologic malignancies, who received the PD-1 inhibitor pembrolizumab as monotherapy (200 mg fixed-dose q3 w) from 2017 to 2020 (n = 48). Thirty-six patients receiving at least four courses were included in the final analysis. Associations between a BMI increase per 5 kg/m2 and overall response rate (ORR; complete + partial response), disease control rate (DCR; ORR + stable disease), progression-free (PFS), and overall survival (OS) were assessed. An elevated BMI was univariately associated with ORR (OR 10.93 [CI 2.39–49.82], p = 0.002), DCR (OR 2.19 [CI 0.99–4.83], p = 0.048), prolonged PFS (HR 1.54 [CI 1.03–2.34], p = 0.038), and OS (HR 1.87 [CI 1.07–3.29], p = 0.028). All results could be confirmed in the multivariate analyses. Pretherapeutic BMI therefore appears to be a promising readily available biomarker to identify patients with PD-L1-positive and/or MMR-deficient gynecologic malignancies who could particularly benefit from CPI treatment

Prostate-Specific Membrane Antigen (PSMA) Expression in Tumor-Associated Neovasculature Is an Independent Prognostic Marker in Patients with Ovarian Cancer

Prostate-specific membrane antigen (PSMA) is present in the tumor-associated neovasculature of many cancer types. Current data in ovarian cancer are limited and controversial; thus, the aim of this study was to investigate PSMA expression in a larger and homogenous patient cohort. This might lead to further studies investigating the use of imaging and therapeutic modalities targeting PSMA. Eighty patients with advanced stage high-grade serous ovarian cancers were included. Using immunohistochemistry, PSMA and CD31, a marker for endothelial cells, were examined in whole tissue sections. Percentage and intensity of PSMA expression were determined in the neovasculature. Expression levels were correlated with clinicopathological parameters and survival. Low (&le;10%), medium (20&ndash;80%), and high (&ge;90%) PSMA expression was found in 14, 46, and 20 ovarian cancer samples, respectively. PSMA expression was confined to tumor-associated neovasculature and significantly correlated with progression-free (HR 2.24, 95% CI 1.32&ndash;3.82, p = 0.003) and overall survival (HR 2.73, 95% CI 1.41&ndash;5.29, p = 0.003) in multivariate models, considering age, FIGO stage, and residual disease. This is the first study showing a clinical relevance for PSMA in patients with ovarian cancer. PSMA was detected in the vast majority of cancer samples and showed an impact on survival

Genetic analyses in a variant of Mayer-Rokitansky-Kuster-Hauser syndrome (MURCS association).

Item does not contain fulltextMayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by the congenital absence of uterus and upper part of the vagina as a result of Mullerian duct agenesis. The combination of MRKH syndrome with renal anomalies and cervicothoracic dysplasia is known as MURCS association (Mullerian aplasia, Renal anomalies, and Cervicothoracic Somite dysplasia). The etiology remains poorly understood. We delineate this disease by reporting on a 16-year-old patient showing the cardinal features of MURCS association accompanied by a persistent left superior vena cava and atrial septal defect, orofacial clefting, and mild reduction deformities of the left hand. Fluorescence in situ hybridization did not show major deletions or duplications of the DiGeorge/VCFS (velocardiofacial syndrome) region at chromosome 22q11.1 as well as the TBX5/TBX3 region at 12q24.1. In addition, sequencing of the TP63L (p63) gene, residing at 3q27, remained normal in the presented patient. Thus, we provide further evidence for the genetic heterogeneity of MURCS association