Angiogenesis, programmed death ligand 1 (PD-L1) and immune microenvironment association in laryngeal carcinoma.

In the specific field of laryngeal carcinoma (LSCC), evidence about the interaction between angiogenetic pathway and immune microenvironment has not yet been explored. Given the potential relevance of such an interaction for prognostic and therapeutic purposes, the main aim of this exploratory study was to investigate the existence of a correlation between angiogenesis (quantified through CD31 expression), programmed cell death ligand 1 (PD-L1) expression, and immune microenvironment. A secondary aim was to verify whether considering a combination of angiogenesis and immune microenvironment variables might improve prognostic accuracy compared to the traditional clinical-pathological prognostic tools. CD31-assessed micro-vessel density (MVD), PD-L1 in terms of combined positive score (CPS), and tumour infiltrating lymphocytes (TILs) were assessed on 45 consecutive cases of LSCC. Cox proportional hazards model revealed increasing CD31-assessed MVD values, PD-L1 CPS <1, and TILs count rate <30%, as predictive of reduced disease free survival (DFS). Multivariate analysis found that MVD (p<0.0001) and TILs (p=0.0420) retained their significant independent prognostic value. Spearman's correlation model disclosed a significant negative correlation between CD31-assessed MVD values and PD-L1 CPS (p=0.0040). PD-L1 CPS and TILs count rate were positively correlated (p<0.0001). DFS was significantly lower in the CD31-assessed MVD >7, PD-L1 CPS <1, TILs <30% group than in the MVD ≤7, PD-L1 CPS ≥1, TILs ≥30% group (p=0.0001). These data preliminarily support an integrated interpretation of the prognostic role or angiogenesis and immune microenvironment markers in LSCC. This is of potential clinical relevance suggesting a synergistic effect of the combination of anti-angiogenic drugs with programmed death-1/PD-L1 checkpoint inhibitors in advanced LSCC.

FOSL2 promotes VEGF-independent angiogenesis by transcriptionnally activating Wnt5a in breast cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAFs), a predominant component of the tumor microenvironment, contribute to aggressive angiogenesis progression. In clinical practice, traditional anti-angiogenic therapy, mainly anti-VEGF, provides extremely limited beneficial effects to breast cancer. Here, we reveal that FOS-like 2 (FOSL2), a transcription factor in breast CAFs, plays a critical role in VEGF-independent angiogenesis in stromal fibroblasts. Methods: FOSL2 and Wnt5a expression was assessed by qRT-PCR, western blotting and immunohistochemistry in primary and immortalized CAFs and clinical samples. FOSL2- or Wnt5a-silenced CAFs and FOSL2-overexpressing NFs were established to explore their proangiogenic effects. Invasion, tubule formation, three-dimensional sprouting assays, and orthotopic xenografts were conducted as angiogenesis experiments. FZD5/NF-κB/ERK signaling activation was evaluated by western blotting after blocking VEGF/VEGFR with an anti-VEGF antibody and axitinib. Dual luciferase reporter assays and chromatin immunoprecipitation were performed to test the role of FOSL2 in regulating Wnt5a expression, and Wnt5a in the serum of the patients was measured to assess its clinical diagnostic value for breast cancer patients. Results: Enhanced FOSL2 in breast CAFs was significantly associated with angiogenesis and clinical progression in patients. The supernatant from CAFs highly expressing FOSL2 strongly promoted tube formation and sprouting of human umbilical vein endothelial cells (HUVECs) in a VEGF-independent manner and angiogenesis as well as tumor growth in vivo. Mechanistically, the enhanced FOSL2 in CAFs was regulated by estrogen/cAMP/PKA signaling. Wnt5a, a direct target of FOSL2, specifically activated FZD5/NF-κB/ERK signaling in HUVECs to promote VEGF-independent angiogenesis. In addition, a high level of Wnt5a was commonly detected in the serum of breast cancer patients and closely correlated with microvessel density in breast tumor tissues, suggesting a promising clinical value of Wnt5a for breast cancer diagnostics. Conclusion: FOSL2/Wnt5a signaling plays an essential role in breast cancer angiogenesis in a VEGF-independent manner, and targeting the FOSL2/Wnt5a signaling axis in CAFs may offer a potential option for antiangiogenesis therapy.

Perifocal edema volume is not associated with immunohistochemical features reflecting proliferation potential, microvessel density, neoangiogenesis and invasiveness in brain metastasis.

OBJECTIVE: Perifocal edema of brain tumors is associated with survival and neurological symptoms. Our aim was to analyze associations between perifocal edema and immunohistochemical features including proliferation potential, microvessel density, neoangiogenesis and invasiveness in brain metastasis (BM). METHODS: 35 patients with BM were included into the retrospective study. The tumors were localized supratentorial in 25 lesions (71.4%) and infratentorial in 10 lesions (28.6%). The following immunohistochemical features were calculated on histopathological specimens: microvessel density, proliferation index Ki 67, matrix-metallopeptidase 9 (MMP9) extracellular matrix metalloproteinase inducer (EMMPRIN) and vascular endothelial growth factor (VEGF) expression. Tumor and edema volumes were estimated semiautomatically on magnetic resonance images. RESULTS: There were no correlations between tumor volume and edema volume. Moreover, no correlation was identified between the investigated immunohistochemical features and tumor/edema volume. In the non-small cell lung cancer subgroup, a positive correlation between tumor volume and VEGF expression was observed (r = 0.52, P = 0.02) and edema volume correlated inversely with MMP9 expression (r = -0.53, P = 0.02). CONCLUSION: In BM, no linear associations exist between tumor volumes, edema volumes and immunohistochemical features reflecting proliferation potential, neoangiogenesis, microvessel density and MMP9 expression. However, in the subgroup of non-small cell lung cancer, there might be associations between MMP9 expression and edema volume as well as between tumor volume and angiogenesis.

Use of MarginProbe as an adjunct to standard operating procedure does not significantly reduce re-excision rates in breast conserving surgery.

PURPOSE: A positive margin after breast conserving surgery has consistently been shown to be a significant predictor for ipsilateral breast tumor recurrence. Currently, there is no standard for intraoperative margin assessment during lumpectomy, and up to 20% of cases result in positive margins. MarginProbe is a device that provides real-time evaluation of lumpectomy margins during surgery. The aim of this study was to evaluate the impact of MarginProbe as an adjunct to standard operating procedure (SOP). METHODS: Patients diagnosed with breast cancer scheduled for breast conserving surgery were consented for intraoperative use of MarginProbe. Shaved margins were excised based on margin assessment using the surgeon's SOP which included specimen radiography and gross pathologic examination, and feedback from the device. The primary endpoint was re-excision rate. Secondary endpoints included sensitivity, specificity, false-positive and negative rates. RESULTS: Of the 60 breast cancers, initial histologically close/positive margins were identified in 18 patients (30%). The re-excision rate in the overall cohort was 6.6%, compared to a historical re-excision rate of 8.6% (p < 0.01). Based on 360 measurement sites, MarginProbe demonstrated a sensitivity of 67% and specificity of 60%, with a positive predictive value of 16%, and of negative predictive value of 94%, which was similar to the accuracy of SOP. CONCLUSIONS: MarginProbe performs equally as well as specimen radiography and gross pathologic examination. In this setting where the baseline re-excision rate was low, the use of MarginProbe as an adjunct to SOP resulted in a small 2% absolute reduction in re-excision rate.

Antidiastole Value of Three-dimensional Ultrasonography and Power Doppler between Uterine Parenchyma Lumps and Endometrial Cancer: A Retrospective Study.

Sometimes endometrial polyps, submucosal myomas, and endometrial cancer show similar findings under ultrasonography. The aim of this study was to assess the antidiastole value of blood flow parameters using three-dimensional (3D) power Doppler ultrasonography angiography (PDA) between endometrial cancer and uterine parenchyma lumps. The data of the blood flow indices in 3D-PDA including the vascularization index (VI), flow index (FI), and vascularization flow index (VFI) in 40 patients with endometrial cancer and 41 patients with uterine parenchyma lumps (endometrial polyps and submucosal myomas) were retrospectively analysed and compared utilizing Virtual Organ Computer-aided AnaLysis (VOCAL) software. The results showed that all the blood flow parameters (VI, FI, VFI) were significantly higher in women with endometrial cancer than in those with uterine parenchyma lumps (P<0.001). The area under the curve of ROC of VI, FI, and VFI was 0.98, 0.84, and 0.97, respectively. Thus, the best predictor of endometrial carcinoma was VI with a sensitivity of 97.0% and a specificity of 91.0%. The optimal cutoff value of VI was 4.06%. Our data demonstrated that all of the blood flow signal parameters (including VI, FI, and VFI) in 3D power Doppler ultrasonography had significant antidiastole values between endometrial cancer and uterine parenchyma lumps to assist clinicians in properly diagnosing patients.

The clinicopathological significance of ubiquitin-conjugating enzyme E2C, leucine-rich repeated-containing G protein-coupled receptor, WW domain-containing oxidoreductase, and vasculogenic mimicry in invasive breast carcinoma.

Ubiquitin-conjugating enzyme E2C (UBE2C), a crucial part of the ubiquitin-conjugating enzyme complex, is reported to promote progression of various cancers. Leucine-rich repeated-containing G protein-coupled receptor (LGR5), a biomarker of cancer stem cells, is reported to be responsible for the initiation and progression of cancers. WW domain-containing oxidoreductase (WWOX), a suppressor of tumor, is reported to inhibit initiation and progression of cancers. Vasculogenic mimicry (VM), a new blood supply pattern, is associated with progression of cancers. However, the clinicopathological significance of UBE2C, LGR5, WWOX, and VM in invasive breast carcinoma (IBC) remains elusive. The aim of this study is to investigate the positive rate of UBE2C, LGR5, WWOX, and VM in IBC and their clinical significance.Positive rates of UBE2C, LGR5, WWOX, and VM in 247 whole IBC samples were detected through immunohistochemistry. Patients data (including clinical, demography, follow-up) were collected.Levels of UBE2C, LGR5, VM, and microvessel density (MVD) were significantly higher, and level of WWOX was significantly lower in IBC specimens when compared with normal mammary gland tissues. Levels of UBE2C, LGR5, VM, and MVD were all positively associated with tumor stages, lymph node metastasis (LNM) stages, tumor grades, and tumor-node-metastasis (TNM) stages, and unfavorably with patients' overall survival (OS) and disease-free survival (DFS). Level of WWOX was negatively associated with tumor stages, LNM stages, grades, and TNM stages, and favorably with patients' OS and DFS. Multivariate analysis indicated that levels of UBE2C, LGR5, VM, MVD, and WWOX, as well as TNM stages were independently prognostic factors for OS and DFS in patients with IBC.UBE2C, LGR5, VM, MVD, and WWOX may be considered as promising indicator of IBC prognosis.

Undifferentiated carcinoma with osteoclast-like giant cells of pancreas: A case report with review of the computed tomography findings.

RATIONALE: Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGCs) of the pancreas is an extremely rare and aggressive pancreatic malignancy. To our knowledge, the computed tomography (CT) findings of this disease have rarely been analyzed. PATIENT CONCERNS: A 65-year-old man who experienced weight loss of about 4 kg over 3 months presented to our clinic. The abdominal ultrasound (US) detected a 5.8 × 5.5 cm well-defined, cystic-solid mass in the head of the pancreas, which had been present for 1 month. DIAGNOSIS: A benign pancreatic tumor was initially suspected on the basis of the US findings. The patient then received serum tumor markers and CT examinations for further diagnosis, including carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), contrast-enhanced CT (CECT) and CT angiography (CTA). His CA199, CEA, and CA125 marker levels were normal, which supported the diagnosis of a benign tumor. CECT showed a well-defined cystic-solid mass in the head of the pancreas, with a slightly enhanced solid portion and pancreatic ductal dilatation, which led us to consider the possibility of a malignant tumor. CTA revealed that the tumor nourishing arteries emitted from the pancreaticoduodenal superior and inferior arteries into the mass. Then, the patient underwent a pancreaticoduodenectomy. Finally, postoperative pathology and immunohistochemistry confirmed UC-OGC of the pancreas. INTERVENTIONS: The patient has been treated by a pancreaticoduodenectomy alone. OUTCOMES: The operation had no complications, and the patient recovered well after surgery. Ten months after surgery, the patient reviewed the CECT, and no recurrence or metastasis was noted. LESSONS: Old patients with cystic-solid lesions in the pancreas should be aware of UC-OGC. CT findings usually show a clear boundary and a slightly enhanced mass with pancreatic duct expansion.

Induction of chemokine (C-C motif) ligand 5 by Epstein-Barr virus infection enhances tumor angiogenesis in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is etiologically associated with Epstein-Barr virus (EBV) infection and is known to be highly vascularized. Previous studies have suggested that EBV oncoproteins contribute to NPC angiogenesis. However, the regulatory network of EBV in angiogenesis still remains elusive. Herein, we reveal a novel mechanism of EBV-induced angiogenesis in NPC. First, we showed that EBV-infected NPC cell lines generated larger tumors with more microvessels in mouse xenograft models. Subsequent proteomic analysis revealed that EBV infection increased the expression of a series of angiogenic factors, including chemokine (C-C motif) ligand 5 (CCL5). We then proved that CCL5 was a target of EBV in inducing tumor angiogenesis and growth. Further investigation through transcriptome analysis indicated that the pro-angiogenic function of CCL5 might be mediated by the PI3K/AKT pathway. Furthermore, we confirmed that activation of the PI3K/AKT and hypoxia-inducible factor-1α pathways was essential for CCL5-promoted angiogenesis. Finally, the immunohistochemical analysis of human NPC specimens also showed that CCL5 was correlated with angiogenesis. Taken together, our study identifies CCL5 as a key EBV-regulated molecular driver that promotes NPC angiogenesis, suggesting it as a potential therapeutic target.

Diagnosis of lymphoepithelial carcinoma in parotid gland with three dimensional computed tomography angiography reconstruction: A case report.

Lymphoepithelial carcinoma (LEC) is an uncommon malignant neoplasm. Due to the complicated anatomical structure of the human head, standard imaging modalities including ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) scan remain limited in detection of salivary tumors. We used three-dimensional computed tomography angiography (3D-CT angiography) for the assessment and pre-operative surgical planning of facial fractures of a case with LEC. The study results demonstrated that 3D-CT angiography provided an insightful approach to preoperative evaluation in the treatment of salivary tumors.

Carbohydrate Antigen 19-9 Increases the Predictive Efficiency of α-Fetoprotein for Prognosis of Resected Hepatocellular Carcinoma.

Serum α-fetoprotein (AFP) is a classical biomarker for both diagnosis and prognosis of hepatocellular carcinoma (HCC). However, its predictive efficiency for prognosis remains unsatisfactory. This study explores whether integrating AFP and carbohydrate antigen (CA) 19-9/carcinoembryonic antigen (CEA) increase its prognostic efficiency in HCC. A total of 67 HCC patients with complete record of AFP, CA19-9, and CEA, who underwent radical hepatectomy, were included. The sole and combined evaluations for prognostic significance of the three markers were performed. In the first, it was found by one-factor analysis that AFP was a univariate prognostic indicator for disease-free survival, but not overall survival, whereas CEA and CA19-9 were not statistically significant, although the latter was of marginally predictive significance for disease-free survival. Subsequently, it was revealed that combined evaluation of AFP and CA19-9, rather than AFP and CEA, distinguished overall and disease-free survival more effectively, compared with single ones. However, this combination was not significant in multivariate Cox regression analysis, thus needing further validation, especially in large-scale prospective investigations. The addition of vascular invasion to AFP/CA19-9 combination might provide enhanced predictive power for disease-free survival. Collectively, these results preliminarily suggest that CA19-9 increases the predictive efficiency of AFP for prognosis of HCC after resection.

Glomeruloid Microvascular Proliferation, Desmoplasia, and High Proliferative Index as Potential Indicators of High Grade Canine Choroid Plexus Tumors.

Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRß, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT.

Quantifying tumour vascularity in non-luminal breast cancers.

AIMS: Microvessel density (MVD), proliferating MVD (pMVD) and vascular proliferation index (VPI) are methods used to quantify tumour vascularity in histopathological sections. In this study, we assessed MVD, pMVD and VPI in non-luminal subtypes of breast cancer. Differences between subtypes were studied, and the prognostic value of each method was assessed. METHODS: All non-luminal subtypes (61 basal phenotype (BP), 60 human epidermal growth factor receptor 2 (HER2) type and 30 five negative phenotype (5NP)) were selected from a series comprising 909 cases of breast cancer. Sections were stained for Ki67 and von Willebrand factor. Associations between MVD, pMVD and VPI, molecular subtypes and prognosis were studied. RESULTS: MVD was highest in 5NP (Δ54.3 microvessels/mm2 compared with BP, 95% CI 30.3 to 78.3), whereas no clear difference was found between HER2 type and BP (Δ8.8 microvessels/mm2, 95% CI -9.6 to 27.1). pMVD and VPI did not differ between subtypes. For MVD, HR was 1.07 (95% CI 1.03 to 1.11) per 10 vessel increase and 1.9 (95% CI 1.2 to 3.1) if MVD was greater than median value. High MVD was associated with poor prognosis in the HER2 type (HR 1.07 (95% CI 1.02 to 1.12)) and 5NP (HR 1.13 (95% CI 1.03 to 1.23)), but not in BP (HR 1.04 (95% CI 0.94 to 1.14) per 10 vessel increase). pMVD and VPI were not associated with prognosis. CONCLUSIONS: MVD appears to be an independent prognostic factor in HER2 and 5NP subtypes of breast cancer, where high MVD is associated with poor survival. MVD was higher in the 5NP compared with both BP and HER2 type.

Evaluation of the correlation of vasculogenic mimicry, ALDH1, KiSS-1, and MACC1 in the prediction of metastasis and prognosis in ovarian carcinoma.

BACKGROUND: Recurrence and metastasis are the usual manifestations of treatment failure of epithelial ovarian carcinoma (EOC). Vasculogenic mimicry (VM; blood supply development often seen in highly aggressive cancers), aldehyde dehydrogenase 1 (ALDH1, cancer stem cell biomarker), KiSS-1 (suppressor of tumor metastasis), and metastasis associated in colon cancer-1 (MACC1) are all useful predictive factors for metastasis and prognosis in various cancers. In this study, we analyzed associations among VM, ALDH1, KiSS-1, and MACC1 in EOC, and their respective correlations with clinicopathological characteristics and survival in EOC. METHODS: Positive rates of VM, ALDH1, KiSS-1, and MACC1 in 207 whole EOC tissue samples were detected by immunohistochemistry. Patients' clinical data were also collected. RESULTS: Levels of VM, ALDH1, and MACC1 were significantly higher, and levels of KiSS-1 significantly lower, in EOC tissues than in benign ovary tumors. Levels of VM, ALDH1, KiSS-1, and MACC1 were associated significantly with tumor/lymph node/metastasis (LNM) grade, implantation, and International Federation of Gynecology and Obstetrics (FIGO) stage, and with patients' overall survival (OS); whereas the KiSS-1+ subgroup had significantly longer OS than did the KiSS-1- subgroup. In multivariate analysis, high VM, ALDH1 or MACC1 levels, FIGO stage, implantation and low KiSS-1 levels were independently associated with shorter OS in patients with EOC. CONCLUSIONS: VM and expressions of ALDH1, KiSS-1, and MACC1 represent promising markers for metastasis and prognosis, and potential therapeutic targets for EOC.

Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases.

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy.

Combination of three-gene immunohistochemical panel and magnetic resonance imaging-detected extramural vascular invasion to assess prognosis in non-advanced rectal cancer patients.

AIM: To identify a small, clinically applicable immunohistochemistry (IHC) panel that could be combined with magnetic resonance imaging (MRI)-detected extramural vascular invasion (EMVI) for assessment of prognosis concerning the non-advanced rectal cancer patients prior to operation. METHODS: About 329 patients with pathologically confirmed rectal carcinoma (RC) were screened in this research, all of whom had been examined via an MRI and were treatment-naïve from July 2011 to July 2014. The candidate proteins that were reported to be altered by RC were examined in tissues by IHC. All chosen samples were adopted from the fundamental cores of histopathologically confirmed carcinomas during the initial surgeries. RESULTS: Of the three proteins that were tested, c-MYC, PCNA and TIMP1 were detected with relatively significant expression in tumors, 35.9%, 23.7% and 58.7% respectively. The expression of the three proteins were closely connected with prognosis (P = 0.032, 0.003, 0.021). The patients could be classified into different outcome groups according to an IHC panel (P < 0.01) via these three proteins. Taking into consideration known survival covariates, especially EMVI, the IHC panel served as an independent prognostic factor. The EMVI combined with the IHC panel could categorize patients into different prognostic groups with distinction (P < 0.01). CONCLUSION: These studies argue that this three-protein panel of c-MYC, PCNA, coupled with TIMP1 combined with MRI-detected EMVI could offer extra prognostic details for preoperative treatment of RC.

68Ga-NODAGA-RGDyK PET/CT Imaging in Esophageal Cancer: First-in-Human Imaging.

Ga-NODAGA-RGDyK(cyclic) and FDG PET/CT were performed in a 39-year-old man for the work-up of a moderately differentiated carcinoma of the gastro-esophageal junction within a clinical study protocol. Although FDG PET images showed intense, diffuse hypermetabolic lesion activity, NODAGA-RGDyK illustrated the neo-angiogenesis process with tracer uptake clearly localized in non-FDG-avid perilesional structures. Neo-angiogenesis is characterized by ανß3 integrin expression at the lesion surface of newly formed vessels. This case supports evidence that angiogenesis imaging might therefore be a crucial step in early disease identification and localization, metastatization potential, and in monitoring the efficacy of antiangiogenic therapies.

Interactive role of miR-126 on VEGF-A and progression of papillary and undifferentiated thyroid carcinoma.

MicroRNA-126 (miR-126) expression has been shown to be associated with angiogenesis. The aim of the current study is to evaluate the functional roles of miR-126 in dysregulation of VEGF expression and cancer progression in thyroid carcinomas. The expression of VEGF-A and miR-126 were measured in 101 thyroid carcinomas tissues (including 51 conventional papillary thyroid carcinoma, 37 follicular variant of papillary thyroid carcinoma, and 13 undifferentiated thyroid carcinomas), 13 matched lymph nodes with metastatic thyroid carcinoma, 21 benign thyroid tissues, and 5 thyroid carcinoma cell lines (both papillary and undifferentiated carcinomas). Then, exogenous miR-126 was transfected, and the expressions of VEGF-A were determined (Western blot technique). Proliferation assay, cell cycle analysis, and apoptosis assays were used to evaluate the role of miR-126 in these events. Significant underexpression of miR-126 levels in thyroid cancer tissues and cell lines was detected using real-time polymerase chain reaction. Introducing exogenous miR-126 into the cancer cell lines resulted in a significant reduction of VEGF-A protein expression. Marked inhibition in proliferation, cell cycle arrest in G0-G1, and promotion of total apoptosis were also noted. The modulatory role of miR-126 on expression of VEGF-A and its tumor suppressive roles were demonstrated for the first time in thyroid cancer. The current experiments provided specific information on the functional consequences of VEGF manipulation via microRNA on cancer.

Vascular invasion is an independent prognostic factor for distant recurrence-free survival in papillary thyroid carcinoma: a matched-case comparative study.

OBJECTIVE: It is still unclear whether the clinicopathological and outcome characteristics of vascular invasion (VI) (+) papillary thyroid carcinoma (PTC) differ from VI (-) PTC. This study aims to establish distinguishing features of patients with VI (+) and VI (-) PTC and to investigate the biological and clinical aggressiveness of the disease in these patient groups. DESIGN: A matched-case comparative study. METHODS: 412 patients (VI (+) PTC study group n=103, and VI (-) PTC control group n=309). These two patient groups were matched 1:3 for variables of age, gender, histological variants, tumour/node/metastasis (TNM) staging and approximate duration of follow-up. Clinicopathological factors and prognosis were compared across the two patient groups. RESULTS: The median age at the time of diagnosis was 42.0 years, and 68.9% were females. Across the patient groups, the incidence of tumour multifocality in patients with VI (+) PTC was slightly higher than in those with VI (-) PTC (p=0.049). In addition, when undergoing more aggressive therapy regimens patients with VI (+) PTC showed decreased distant recurrence-free survival (DRFS), but not regional recurrence-free survival (RRFS) and disease-specific survival (DSS) compared with patients who were VI (-). VI was found to be an independent predictor of DRFS, combined with tumour size >3 cm and total thyroidectomy. CONCLUSIONS: VI was an independent risk factor for DRFS, necessitating the need for appropriate postoperative treatment and careful follow-up.

Clinical and biological significance of HAX-1 overexpression in nasopharyngeal carcinoma.

HS1-associated protein X-1 (HAX-1) is an important marker in many types of cancers and contributes to cancer progression and metastasis. We examined the expression of HAX-1 in nasopharyngeal carcinoma (NPC) and experimentally manipulated its expression. We observed that HAX-1 expression is elevated in NPC and is correlated with lymph node metastasis, M classification, clinical stage, and poor prognosis. In addition, overexpression of HAX-1 promoted NPC proliferation both in vitro and in vivo. Exosomes are potential carriers of pro-tumorigenic factors that participate in oncogenesis. We found that NPC-derived exosomes are enriched in HAX-1 and accelerate NPC tumor growth and angiogenesis in vitro and in vivo. Furthermore, we demonstrated that oncogenic HAX-1 facilitates the growth of NPC when it is transferred via exosomes to recipient human umbilical vein endothelial cells (HUVECs). Oncogenic HAX-1 also increases the proliferation, migration, and angiogenic activity of HUVECs. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as HAX-1 to improve NPC treatment.

Pre-operative embolization of a choroid plexus carcinoma: review of the vascular anatomy.

AIM: The purpose of this case is to highlight the benefits of preoperative embolization as well as to review the vascular anatomy that needs to be recognized in order to perform pre-operative embolization of choroid plexus tumors. METHOD: We achieve this by presenting the case of a 12-month-old female who had symptoms of raised intracranial pressure. MRI demonstrated a large vividly enhancing mass centered within the atria of the right lateral ventricle associated with hydrocephalus in keeping with a choroid plexus tumor. RESULT: Enlarged anterior and posterior choroidal arteries supplying the tumor were noted on the MRI scan. Pre-operative embolization was performed with NBCA glue via the anterior and posterior choroidal arteries. Subsequently, total surgical resection was achieved with only 200 cc of blood loss. Pathology confirmed a choroid plexus carcinoma. CONCLUSION: Pre-operative embolization can be useful in minimizing blood loss during excision of choroid plexus tumors. It is important to understand the anatomy of the anterior and posterior choroidal arteries to perform embolization of these tumors safely.