Pathological Significance of GLUT-1 Expression in Breast Cancer Cells in Diabetic and Obese Patients: The French Guiana Study

The prevalence of obesity and type 2 diabetes is higher in French Guiana compared to mainland France. These metabolic disorders are associated with an increased risk of cancer. One of the factors involved is hyperinsulinemia that promotes the action of glucose transporter 1 (GLUT-1). The objective of this study is to characterize the expression of GLUT-1 in breast cancers cells in diabetic and obese patients compared to those who are not and to describe the clinical and histological prognostic factors of breast cancer in this population. We conducted a monocentric study including patients with breast cancer diagnosed between 2014 and 2020. Patients were classified into three groups: diabetes, obesity, and control group. The GLUT-1 expression was assessed by immunohistochemistry. In total, 199 patients were included in this study. The median age was 53.5 years, and the median tumor size was 2.8 cm. Luminal A was the most frequent molecular type (58.1%), followed by the triple-negative type (19.9%). The breast cancer in our population was characterized by a younger age at diagnosis, more aggressive molecular types, and larger tumor size. Thus, we suggest the advancement of the age of breast cancer screening in this territory. A total of 144 patients (31 diabetes, 22 obese, and 91 control group) were included for the study of GLUT-1 expression. Overexpression of GLUT-1 was observed in 60.4% of cases and in all carcinoma in situ lesions. GLUT-1 overexpression was associated with more aggressive cancers. This overexpression is correlated with high histological grade, high proliferation index, and aggressive molecular types. Our study found no difference in GLUT-1 expression between the diabetic or obese patients and the control group. These results highlight the potential role of GLUT-1 as a tumor metabolic prognostic marker and also as an interesting target therapy, independently of patient metabolic disorder.

Modeling of Interstitial Microwave Hyperthermia for Hepatic Tumors Using Floating Sleeve Antenna

PurposeMicrowave hyperthermia is a treatment modality that uses microwaves to destroy cancer cells by increasing their temperature to 41- 45°C. This study aims to design, modeling, and simulation of a microwave sleeve antenna for hepatic (liver) hyperthermia. MethodThe designed antenna resonated at 2.45 GHz. The antenna was tested in six different 3D liver models: Model A: without a tumor and blood vessels; Model B: with a realistic tumor (2x3 cm) and without blood vessels; Model C: created by adding blood vessels to model B; Model D: created by adding a small tumor (1.5x1.5 cm) to model C and changed its location; Model E: same as model C with a different tumor size; Model F: model with a simple spherical tumor (1.5x1.5 cm).ResultsThe return loss of the antenna varied from -45 dB to -25 dB for the 6 models. The Specific Absorption Rate (SAR) was between 29 W/kg to 30W/kg in the tumors and below 24 W/Kg in the surrounding tissues. The tumors’ temperature elevated to 43- 45°C, while the temperature of the surrounding tissues was below 41°C.ConclusionsThe results showed the capability of the designed antenna to raise the temperature of hepatic tumors to the therapeutic ranges of hyperthermia.

New Insights into LINC00346 and its Role in Disease

Accumulating evidence has shown that long intergenic non-protein-coding RNA 346 (LINC00346) functions as an oncogene in the tumorigenesis of several cancers. The expression level of LINC00346 has been shown to be obviously correlated with prognosis, lymphoma metastasis, histological grade, TNM stage, tumor size and pathologic stage. LINC00346 has been found to regulate specific cellular functions by interacting with several molecules and signaling pathways. In this review, we summarize recent evidence concerning the role of LINC00346 in the occurrence and development of diseases. We also discuss the potential clinical utility of LINC00346, thereby providing new insight into the diagnosis and treatment of diseases. In addition, we further discuss the potential clinical utility of LINC00346 in the diagnosis, prognostication, and treatment of diseases.

A Web-Based Prediction Model for Cancer-Specific Survival of Elderly Patients With Hypopharyngeal Squamous Cell Carcinomas: A Population-Based Study

Background: Hypopharyngeal squamous cell carcinomas (HPSCC) is one of the causes of death in elderly patients, an accurate prediction of survival can effectively improve the prognosis of patients. However, there is no accurate assessment of the survival prognosis of elderly patients with HPSCC. The purpose of this study is to establish a nomogram to predict the cancer-specific survival (CSS) of elderly patients with HPSCC.Methods: The clinicopathological data of all patients from 2004 to 2018 were downloaded from the SEER database. These patients were randomly divided into a training set (70%) and a validation set (30%). The univariate and multivariate Cox regression analysis confirmed independent risk factors for the prognosis of elderly patients with HPSCC. A new nomogram was constructed to predict 1-, 3-, and 5-year CSS in elderly patients with HPSCC. Then used the consistency index (C-index), the calibration curve, and the area under the receiver operating curve (AUC) to evaluate the accuracy and discrimination of the prediction model. Decision curve analysis (DCA) was used to assess the clinical value of the model.Results: A total of 3,172 patients were included in the study, and they were randomly divided into a training set (N = 2,219) and a validation set (N = 953). Univariate and multivariate analysis suggested that age, T stage, N stage, M stage, tumor size, surgery, radiotherapy, chemotherapy, and marriage were independent risk factors for patient prognosis. These nine variables are included in the nomogram to predict the CSS of patients. The C-index for the training set and validation was 0.713 (95% CI, 0.697–0.729) and 0.703 (95% CI, 0.678–0.729), respectively. The AUC results of the training and validation set indicate that this nomogram has good accuracy. The calibration curve indicates that the observed and predicted values are highly consistent. DCA indicated that the nomogram has a better clinical application value than the traditional TNM staging system.Conclusion: This study identified risk factors for survival in elderly patients with HPSCC. We found that age, T stage, N stage, M stage, tumor size, surgery, radiotherapy, chemotherapy, and marriage are independent prognostic factors. A new nomogram for predicting the CSS of elderly HPSCC patients was established. This model has good clinical application value and can help patients and doctors make clinical decisions.

Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes

HER2+ breast cancer (BC) is an aggressive subtype representing a genetically and biologically heterogeneous group of tumors resulting in variable prognosis and treatment response to HER2-targeted therapies according to estrogen (ER) and progesterone receptor (PR) expression. The relationship with androgen receptors (AR), a member of the steroid hormone’s family, is unwell known in BC. The present study aims to evaluate the prognostic impact of AR expression in HER2+ BC subtypes. A total of 695 BCs were selected and reviewed, AR, ER, PR and HER2 expression in tumor cells were examined by immunohistochemical method, and the SISH method was used in case of HER2 with equivocal immunohistochemical score (2+). A high prevalence of AR expression (91.5%) in BC HER+ was observed, with minimal differences between luminal and non-luminal tumor. According to steroid receptor expression, tumors were classified in four subgroups, including BC luminal and non-luminal HER2+ expressing or not AR. The luminal BC HER2 + AR+ was associated with lower histological grade, lower tumor size, higher PR expression and lower HER2 intensity of expression (2+). Also, the non-luminal tumors AR+ showed lower tumor size and lower prognostic stage but frequently higher grade and higher HER2 intensity of expression (3+). These findings should suggest a different progression of luminal and non-luminal tumors, both expressing AR, and allow us to speculate that the molecular mechanisms of AR, involved in the biology of BC HER2 + AR+, differ in relation to ER and PR expression. Moreover, AR expression may be a useful predictor of prognosis for overall survival (OS) in HER2+ BC subtypes. Our findings suggest that AR expression evaluation in clinical practice could be utilized in clinical oncology to establish different aggressiveness in BC HER2+ subtypes.

WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas

BackgroundWhile molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting.Material and MethodsA total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. IDH mutations, codeletion of chromosomal arms 1p/19q, and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions were analyzed.ResultsThere was no survival benefit for patients with WHO grade 2 over grade 3 IDH-mut dLGG after exclusion of tumors with known CDKN2A/B homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In IDH-mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01–1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00–1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00–1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01–1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08).ConclusionOur findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both IDH-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in IDH-mut astrocytomas only. The age cutoffs for determining high risk in patients with IDH-mut dLGG from the pre-molecular era are not supported by our results.

Impact of Treatment Modalities Upon Survival Outcomes in Skull Base and Clival Chordoma: An NCDB Analysis

Objectives: Skull base chordomas are locally aggressive malignant tumors derived from the notochord remnant. There are limited large-scale studies examining the role and extent of surgery and radiation therapy. Design: Analysis of the National Cancer Database (NCDB) was performed to evaluate the survival outcomes of various treatments, and to assess for predictors of overall survival (OS). Participants: Retrospective, population-based cohort study of patients diagnosed with a clival/skull base chordoma between 2004-2015 in the NCDB. Main Outcome Measures: The primary outcome was overall survival (OS). Results: 468 cases were identified. 49% of patients received surgery and 20.7% had positive margins. Mean age at diagnosis was 48.4 years in the surgical cohort, and 55% were male. Of the surgical cohort, 33.8% had negative margins, 20.7% had positive margins, and 45.5% had unknown margin status. Age ≥ 65 (HR 3.07, 95% CI 1.63-5.76, p<0.001), diagnosis between 2010-2015 (HR 0.49, 95% CI 0.26-0.90, p=0.022), tumor size >5 cm (HR 2.29, 95% CI 1.26-4.15, p=0.007) and government insurance (HR 2.28, 95% CI 1.24-4.2, p=0.008) were independent predictors of OS. When comparing surgery with or without adjuvant radiation, no survival differences were found, regardless of margin status (P=0.66). Conclusions: Surgery remains the mainstay of therapy. Advanced age over 65, large tumor size, and government insurance were predictors of worse OS. While negative margins and the use of adjuvant radiation did not appear to impact OS, these may very well reduce local recurrences. A multidisciplinary approach is critical in achieving optimal outcomes in this challenging disease.

Characteristics and nomogram for primary lung lepidic adenocarcinoma

Background: Lepidic adenocarcinoma (LPA) is an infrequent subtype of invasive pulmonary adenocarcinoma (ADC). However, the clinicopathological features and prognostic factors of LPA have not been elucidated.Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database of 4087 LPA patients were retrospectively analyzed and compared with non-LPA pulmonary ADC to explore the clinicopathological and prognosis features of LPA. Univariate and multivariate Cox proportional hazard models were performed to identify independent survival predictors for further nomogram development. The nomograms were validated by using the concordance index, receiver operating characteristic curves, and calibration plots, as well as decision curve analysis, in both the training and validation cohorts.Results: Compared with non-LPA pulmonary ADC patients, those with LPA exhibited unique clinicopathological features, including more elderly and female patients, smaller tumor size, less pleural invasion, and lower histological grade and stage. Multivariate analyses showed that age, sex, marital status, primary tumor size, pleural invasion, histological grade, stage, primary tumor surgery, and chemotherapy were independently associated with overall survival (OS) and cancer-specific survival (CSS) in patients with LPA, while race was the only independent prognostic factor for OS, not for CSS. The nomograms showed good accuracy compared with the actual observed results and demonstrated improved prognostic capacity compared with TNM stage.Conclusions: Patients with LPA are more likely to be older and female. Smaller tumor size, lower histological grade and stage are the clinicopathological features of LPA, which may indicate a good prognosis. The constructed nomograms accurately predict the long-term survival of LPA patients.

A Real-World Comparative Study of Microwave and Radiofrequency Ablation in Treatment-Naïve and Recurrent Hepatocellular Carcinoma

The efficacy and safety of microwave ablation (MWA) compared to radiofrequency ablation (RFA) for patients with treatment-naïve and recurrent hepatocellular carcinoma (HCC) has not been clarified in Korea. There were 150 HCC patients (100 in the RFA group and 50 in the MWA group) enrolled in our study. The primary outcome was one- and two-year disease-free survival (DFS). Secondary outcomes were complete response (CR) rate, two-year survival rate, risk factors for DFS and complication rate. Treatment outcomes were also assessed using propensity-score matching (PSM). The MWA group had better one- and two-year DFS than the RFA group (p = 0.035 and p = 0.032, respectively), whereas the CR rate, two-year survival rate, and complication rate were similar between the two groups with fewer major complications in the MWA group (p = 0.043). Patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. MWA was also an independent factor for favorable one- and two-year DFS. Finally, the MWA group still showed better one- and two-year DFS than the RFA group after PSM. In conclusion, MWA could be an alternative treatment to RFA especially in patients with a high risk of recurrence, perivascular tumors, and small tumor size.