PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 Deubiquitination

Regenerating liver phosphatase 1 (PRL1) is an established oncogene in various cancers, although its biological function and the underlying mechanisms in glioblastoma multiforme (GBM) remain unclear. Here, we showed that PRL1 was significantly upregulated in glioma tissues and cell lines, and positively correlated with the tumor grade. Consistently, ectopic expression of PRL1 in glioma cell lines significantly enhanced their tumorigenicity and invasion both in vitro and in vivo by promoting epithelial-mesenchymal transition (EMT). Conversely, knocking down PRL1 blocked EMT in GBM cells, and inhibited their invasion, migration and tumorigenic growth. Additionally, PRL1 also stabilized Snail2 through its deubiquitination by activating USP36, thus revealing Snail2 as a crucial mediator of the oncogenic effects of PRL1 in GBM pathogenesis. Finally, PRL1 protein levels were positively correlated with that of Snail2 and predicted poor outcome of GBMs. Collectively, our data support that PRL1 promotes GBM progression by activating USP36-mediated Snail2 deubiquitination. This novel PRL1/USP36/Snail2 axis may be a promising therapeutic target for glioblastoma.

Correlation Between Cyclin D1 Expression With Different Pathological Changes in Colorectum Patients

Background: Cyclin D1 plays a vital role in cancer cell cycle progression and is overexpressed in many human cancers, including colorectal cancer. Objectives:This study was aimed to detect cyclin D1 in colorectal cancer patients and to correlate cyclin D1 expression with different pathological changes in colorectum.Methods: Tissues microarray paraffin block with 48 colorectal cancer samples were retrieved from the archives of Elrahma Medical Center. The cyclin D1 was analyzed.Results:Cyclin D1 did not correlate with pathological alterations and with tumor grade.Conclusion:Results indicated that; cyclin D1 not correlates with pathological alteration of colorectal cancer.

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma—A Proof of Principle Study

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

Mucoepidermoid Carcinomas of the Larynx

Objectives: Discussions regarding the specific management and outcomes for laryngeal MEC are limited to very small, single-institution case series. To look further into the diagnosis and management of these uncommon non-squamous cell carcinomas of the larynx, we present 3 recent cases of laryngeal MEC treated at our institution. Methods: Patients at a tertiary hospital treated for MEC between October 2019 and December 2020 were retrospectively identified. Chart review, imaging analysis, and histologic slide creation were completed for all patients. Results: We identified and treated 2 patients with high-grade supraglottic and 1 patient with intermediate-grade glottic MEC. These patients presented to our clinic with a primary complaint of either gradual, worsening dysphonia, dysphagia, or both. All patients underwent laryngovideostroboscopy as well as panendoscopy with directed submucosal biopsy, which was consistent with MEC. MRI was performed in 2 of the cases further elucidating the extent of submucosal spread. PET-CT was performed in all 3 cases, and none demonstrated evidence of regional or distal metastases. Surgically, high-grade MEC lesions were treated with a total laryngectomy. The intermediate MEC lesion was managed with a supracricoid partial laryngectomy (SCPL). Surgical margins were free of tumor in all cases with no nodal metastases by modified radical neck dissection. Radiation therapy was offered to both high-grade MEC patients and declined by one. Radiation was not recommended to the patient with intermediate-grade MEC as we believed that the risk of additional treatment outweighed the benefit. Conclusion: We believe that MEC of the larynx should be considered in patients with atypical submucosal laryngeal masses. Laryngovideostroboscopy, MRI, and PET imaging may be valuable in determining the extent of the lesions and planning appropriate surgery. Postoperative radiation therapy should be considered a per tumor grade in other more studied sites, as there is no data on efficacy in laryngeal MEC.

The diagnostic value of core needle biopsy in cervical cancer: A retrospective analysis

Cervical carcinoma is a major cause of morbidity and mortality among women worldwide. Histological subtype, lymphovascular space invasion and tumor grade could have a prognostic and predictive value for patients’ outcome and the knowledge of these histologic characteristics may influence clinical decision making. However, studies evaluating the diagnostic value of various biopsy techniques regarding these parameters of cervical cancer are scarce. We reviewed 318 cases of cervical carcinoma with available pathology reports from preoperative core needle biopsy (CNB) assessment and from final postoperative evaluation of the hysterectomy specimen. Setting the postoperative comprehensive pathological evaluation as reference, we analysed CNB assessment of histological tumor characteristics. In addition, we performed multivariable logistic regression to identify factors influencing the accuracy in identifying LVSI and tumor grade. CNB was highly accurate in discriminating histological subtype. Sensitivity and specificity were 98.8% and 89% for squamous cell carcinoma, 92.9% and 96.6% for adenocarcinoma, 33.3% and 100% in adenosquamous carcinoma respectively. Neuroendocrine carcinoma was always recognized correctly. The accuracy of the prediction of LVSI was 61.9% and was positively influenced by tumor size in preoperative magnetic resonance imaging and negatively influenced by strong peritumoral inflammation. High tumor grade (G3) was diagnosed accurately in 73.9% of cases and was influenced by histological tumor type. In conclusion, CNB is an accurate sampling technique for histological classification of cervical cancer and represents a reasonable alternative to other biopsy techniques.

Expression of FAP in Lung Cancer and Its Correlation With the Tumor Glucose Metabolism and the Histopathology

Purpose To explore the expression of fibroblast activation protein (FAP) in lung cancer (LC) and its correlation with tumor glucose metabolism and histopathology.Methods From June 2018 to November 2020, a total of 73 patients with newly diagnosed LC were included. Immunohistochemical staining was used to quantify the FAP expression in the tumors. The histopathological type and tumor grade were determined on the histopathological examination. Tumor glucose metabolic parameters and tumor maximal diameter were measured on [18F] F-FDG PET/CT. Univariate and multivariate analysis were used to study the correlation between FAP expression level and glucose metabolic variables and various histopathology.Results Positive FAP expression was observed in 97.3% (71/73) of LC lesions, which was significantly higher than 87.7% (64/73) of [18F] F-FDG positivity on PET/CT (χ2=4.818, P=0.028). In 12 early adenocarcinomas (ADCs), only 3 lesions (25%) were positive on PET/CT, however, 10 lesions (83.3%) were positive with FAP expression. When FAP expression was classified to low level (scores≤3) and high level (scores>4), high FAP level was found in 80.8% tumors and low FAP level in other 19.2% tumors. High FAP level was identified in 100.0% of squamous cell carcinoma (SCC), 85.7% of ADCs, 66.7% (4/6) of large cell neuroendocrine carcinoma (LCNC) and 40.0% (4/10) of small cell lung cancer (SCLC)(P<0.05). In the non-mucinous ADC lesions, on univariate analysis, FAP expression level showed close relationships with tumor metabolism parameters (SUVmax, SUVmean, and TLG), tumor diameter, tumor grade and lesion attenuation (P<0.05).Conclusion The present study demonstrates that FAP expresses widely in LC and has a great variant level in different histopathological types. High positive rate of FAP expression implies FAP targeted imaging may be a sensitive modality for diagnosing LC, especially for early ADCs, and may serve as an alternative of [18F] F-FDG PET/CT.

Study on PI3k gene expression in breast cancer samples and its association with clinical factors and patient survival

Breast cancer is the most common cancer among women in the world. The phosphatidylinositol 3-Kinase (PI3k), which regulates various cellular signaling pathways, is often elevated in human cancers. This study aimed to evaluate the expression of the PI3k gene in breast cancer. In this case-control study, 40 paraffin-embedded tissues of breast cancer and 40 adjacent non-tumor tissues were examined. After total RNA extraction and cDNA synthesis, the relative expression of the gene was obtained using the real-time-PCR method and evaluated by the 2-ΔΔCT method. Also, the association of gene expression with clinical factors and survival rate was investigated. Data analysis was performed by SPSS statistical software (version 22), t-test, and ANOVA. A p-value of less than 0.05 was considered significant. The results showed that PI3k expression was significantly increased in breast tumor tissues compared to non-tumor tissues (p = 0001). Consistent with these results, PI3k expression was associated with metastasis (p = 0.008) and high tumor grade (p = 0.01). In addition, increasing PI3k expression decreased overall survival compared to its low expression (p = 0.03). In general, PI3k plays a tumor-enhancing role in the progression of breast cancer. In addition, increased PI3k expression is associated with metastasis and poor prognosis of cancer, so that PI3k may be useful in the diagnosis, treatment, and prognosis of people with the disease. However, further investigation is needed to substantiate this claim.

Patterns of Distant Metastases in Patients With Triple-Negative Breast Cancer –– A Population-Based Study

Background Currently, the prognosis of triple-negative breast cancer (TNBC) patients remained poor mainly due to resistance, recurrence, metastasis and severe side effects. The study provided systematic insights into the patterns of TNBC distant metastases (DM), as well as investigating the related elements for the prognosis prediction of TNBC patients on the basis of on large sample. Methods We screened eligible patients with triple-negative breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Besides, we analyzed differences in baseline characteristics among patients with diverse modes of metastasis. Meanwhile, we calculated proportional mortality ratio (PMR) and the expression of proportional trends in different patients. Subsequently, Kaplan-Meier (KM) analysis was employed to investigate the survival outcomes. Finally, the predictive and prognostic factors of DM were identified. Results In this study, we included 24,822 TNBC patients, including 1,026 DM patients and 23,796 non-DM patients. At the time of initial diagnosis, 4.1% of patients had DM, and 36.9% had multiple metastases. According to the study, the most common sites of metastasis in DM patients were bone (251 cases) and lung (244 cases), while the least common organ of metastasis was brain (37 cases). Age, tumor grade, T, N and marital status were deemed as risk elements of DM. T stage, insurance status, marital status, surgery treatment, chemotherapy, number of metastatic sites and metastatic sites also effect the diagnosis of DM significantly. Conclusion Our study showed that the most common site of metastasis in TNBC patients with DM was bone and the least common site was brain. Different modes of metastasis have different survival and prognostic characteristics. Thus, our research may have important implications for the clinical practice of TNBC patients in the future.

Trends in HPV Testing for Patients With Sinonasal Squamous Cell Carcinoma: A National Analysis

Objective The objective of this study was to analyze national trends in human papillomavirus (HPV) testing for patients diagnosed with sinonasal squamous cell carcinoma (SNSCC). Study Design Retrospective database study. Setting National Cancer Database (2010-2016). Methods Cases from 2010 to 2016 with a primary SNSCC diagnosis and known HPV testing status were extracted from the National Cancer Database. Univariate and multivariate analyses were then performed to assess differences in socioeconomic, hospital, and tumor characteristics between tested and nontested patients. Results A total of 2308 SNSCC cases were collected, with 1210 (52.4%) HPV tested and 1098 (47.6%) not tested. On univariate analyses, patient age, insurance, income quartile, population density, treatment facility location, and tumor grade were significantly associated with HPV testing status. After multivariate logistic regression modeling, living in a suburban area had lower odds of HPV testing as compared with living in urban areas (odds ratio, 0.74 [95% CI, 0.55-0.99]; P = .041), while tumor grade III/IV had higher odds than grade I (odds ratio, 1.73 [95% CI, 1.29-2.33]; P < .001). HPV-tested patients had a similar 5-year overall survival to nontested patients (48.3% vs 45.3%, log-rank P = .405). A sharp increase in HPV testing rates was observed after 2010 ( P < .001). Conclusion Among patients with SNSCC, those with high-grade tumors were more likely to be tested for HPV, while patients with a suburban area of residence were less likely. Additionally, there was no significant survival benefit to HPV testing, with tested and nontested groups having similar overall survival. Level of evidence 4.

The Expression of Glutaminases and their Association with Clinicopathological Parameters in the Head and Neck Cancers

Background: The increased glutamine metabolism is a characteristic feature of cancer cells. The interconversion between glutamine and glutamate is catalyzed by two glutaminase isoforms, GLS1 and GLS2, which appear to have different roles in different types of cancer. We investigated for the first time the protein expression of GLS1 and GLS2, and their correlation with advanced clinicopathological parameters in head and neck cancers. Method: Consecutive slides from a tissue microarray comprised of 80 samples ranging from normal to metastatic, were stained immunohistochemically for GLS1, GLS2, HIF-1α or CD147. Following analysis by two expert pathologists we carried out statistical analysis of the scores. Results: GLS1 and GLS2 are upregulated at protein level in head and neck tumours compared to normal tissues and this increased expression correlated positively (GLS1) and negatively (GLS2) with tumor grade, indicating a shift of expression between GLS enzyme isoforms based on tumor differentiation. Increased expression of GLS1 was associated with high CD147 expression; and elevated GLS2 expression was associated with both high CD147 and high HIF-1α expressions. The correlation of the GLS1 and GLS2 with HIF-1α or CD147 was strongly associated with more advanced clinicopathological parameters. Conclusion: The increased expression of GLS1 and GLS2 may be explored as a new treatment for head and neck cancers.