Lymph Node Metastatic Potential Research Articles

Two cases of pediatric epithelioid sarcoma of the hand and coverage with Integra

Epithelioid sarcoma is an uncommon soft tissue tumor of the hand characterized by high frequency misdiagnosis and high potential for local recurrence and regional lymph node metastasis. The recommended treatment is wide excision, which leaves complex tissue defects with tendon or neurovascular structure exposure requiring coverage. We present two patients who had tumor excision followed by wound coverage with dermal regeneration template and split-thickness skin graft. Integra® template represents a different approach, which provides a safe, reliable and effective means of soft tissue coverage of the hand.

O-GlcNAcylation promotes colorectal cancer metastasis via the miR-101-O-GlcNAc/EZH2 regulatory feedback circuit

Advanced colorectal cancer (CRC) is one of the deadliest cancers, and the 5-year survival rate of patients with metastasis is extremely low. The epithelial–mesenchymal transition (EMT) is considered essential for metastatic CRC, but the fundamental molecular basis underlying this effect remains unknown. Here, we identified that O-GlcNAcylation, a unique posttranslational modification (PTM) involved in cancer metabolic reprogramming, increased the metastatic capability of CRC. The levels of O-GlcNAcylation were increased in the metastatic CRC tissues and cell lines, which likely promoted the EMT by enhancing EZH2 protein stability and function. The CRC patients with higher levels of O-GlcNAcylation exhibited greater lymph node metastasis potential and lower overall survival. Bioinformatic analysis and luciferase reporter assays revealed that both O-GlcNAcylation transferase (OGT) and EZH2 are posttranscriptionally inhibited by microRNA-101. In addition, O-GlcNAcylation and H3K27me3 modification in the miR-101 promoter region further inhibited the transcription of miR-101, resulting in the upregulation of OGT and EZH2 in metastatic CRC, thus forming a vicious cycle. In this study, we demonstrated that O-GlcNAcylation, which is negatively regulated by microRNA-101, likely promotes CRC metastasis by enhancing EZH2 protein stability and function. Reducing O-GlcNAcylation may be a potential therapeutic strategy for metastatic CRC.

Abstract P5-07-05: LOC283299 suppress the lymphnode metastatic cascade in breast cancer patients

Abstract Background Long non-coding RNAs (lncRNAs) have been proved to play an essential role in cancer metastasis. The accuracy of intraoperative assessment of lymph nodes metastasis need to be improved. In this study, we aimed to define the lncRNA biomarker ectopic expressed in breast cancer patients' metastatic lymph nodes, and to explore the potential molecular mechanisms. Experimental Design RNA-seq analyses in 3 paired breast cancer patients' primary tumor and metastatic lymph node was used as training set to determine differentially expressed lncRNAs that may be associated with lymph node metastasis. The other 40 patients were analyzed as validation set to test the accuracy of lncRNAs identification by quantitative real-time PCR. The correlation between LOC283299 expression level and prognosis in other 282 breast cancer patients was confirmed. In parallel, in vitro and in vivo analyses were carried out to determine the potential mechanisms of LncRNA-dependent lymph node metastases and prognosis. Results RNA-seq analyses in the training set revealed significant correlation between high expression level of LOC283299 and lower lymph node metastasis potential in breast cancer patients. We further validated that the expression level of LOC283299 was significantly higher in tumor primary tissue than that in paired metastatic lymph node (P=0.0245), and higher LOC283299 expression level was markedly associated with good metastasis-free survival in breast cancer patients (P=0.04). In breast cancer cell lines, CRISPR-on overexpression of LOC283299 inhibited proliferation, migration, invasion, and metastases both in vivo and in vitro. shRNA knockdown LOC283299 promotes the ability of tumor proliferation and metastasis. The molecular mechanisms by which LOC283299 as metastasis-suppressing lncRNAs regulates recurrence and metastasis may involve regulation of epithelial to mesenchymal transition (EMT), cellular invasion and microenvironment in breast cancer cells. Conclusion Our study revealed a strong correlation between LOC283299 expression and lymph node metastases in breast cancers. High level of LOC283299 was associated with better metastasis-free survival. The changed metastasis phenotype may be mediated by the interaction of LOC283299 and breast cancer cells. Therefore, LOC283299 may represent a potential predictive biomarker for early lymph node metastasis in breast cancer. Citation Format: Guo R, Xue J, Su Y, Xiu B, Ji W, Chi Y, Wu J. LOC283299 suppress the lymphnode metastatic cascade in breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-05.

Lung Metastasectomy in Pulmonary Metastatic Colorectal Carcinoma

Patients with colorectal cancer are often affected by liver and lung metastases. Besides systemic therapies, lung metastasectomy is a suitable treatment option after complete resection of primary colorectal carcinoma and even concomitant liver metastases. We have performed a systematical literature research of all studies published after 01. 01. 2010. Studies reporting on at least 100 patients undergoing lung metastasectomy after 01. 01. 2000 have been included in our final analysis. Operative data, survival data and prognostic factors have been extracted. Eleven study cohorts reporting on 2,891 patients could be included in the final analysis. Complete resection could be achieved in most cases and thoracic surgeons preferred subsegmental resections. Pathological examination revealed thoracic lymph node involvement in 2.3 to 18.2% of patients. The postoperative mortality varied from 0 to 0.5%. The median follow up ranged between 27.5 and 65.1 months. Pulmonary metastasectomy resulted in 5-year survival rates of 53 to 75.5% and 5-year progression-free survival rates of 33 to 50.9%. Intrathoracic recurrence occurred in 25.2 to 42.9% of patients with complete resection and five-year survival rates ranged from 49 to 75.5% after repeat pulmonary metastasectomy. Analysis of prognostic factors revealed that number, size and distribution of lung metastases are minor important prognostic factors. Moreover, current data suggest disadvantageous post-metastasectomy survival for patients with elevated pre-metastasectomy serum CEA level or intrathoracic lymph node metastases in comparison with the control groups. Nevertheless, even in these patients, lung metastasectomy might be a beneficial procedure. In patients with colorectal cancer and resectable isolated lung or combined liver and lung metastases pulmonary resection should be the treatment of choice. Pulmonary metastasectomy should be combined with thoracic lymph node resection to remove potential lymph node metastases. Repeat metastasectomy should be offered to patients suffering from isolated intrathoracic recurrence.

Distinct histopathological characteristics in colorectal submucosal invasive carcinoma arising in sessile serrated adenoma/polyp and conventional tubular adenoma.

The histopathological characteristics of colorectal submucosal invasive carcinoma arising in sessile serrated adenoma/polyp (SSA/P), a rare malignant tumour, have not yet been fully elucidated. To investigate the features of such, we retrospectively analysed 40 submucosal invasive carcinomas with SSA/P (CA-SSA/P) and compared them to 129 cases of submucosal invasive carcinoma with conventional tubular adenoma (CA-AD). We additionally performed hMLH1 immunostaining. CA-SSA/Ps were significantly smaller than CA-ADs (P<0.001). Histologically, well to moderately differentiated adenocarcinoma was predominant in both CA-SSA/Ps and CA-ADs. No significant differences in depth of invasion were found between the two groups. However, lymphatic invasion was more often found in CA-SSA/Ps (30%) than in CA-ADs (13%; P=0.028), as was lymph node metastasis (CA-SSA/Ps, 28%; CA-ADs, 7%; P=0.011). Furthermore, mucinous component and serrated architecture were significantly more frequent in CA-SSA/Ps (30 and 63%) than in CA-ADs (5 and 18%; P<0.001, respectively). Tumour-infiltrating lymphocytes and Crohn-like inflammatory reaction were also more frequently found in CA-SSA/Ps (70 and 30%) than in CA-ADs (31 and 9%; P≤0.001, respectively), whereas the opposite was true of desmoplastic reaction (CA-SSA/Ps, 35%; CA-ADs, 67%; P<0.001). Loss of hMLH1 expression was more frequent in CA-SSA/P cases (93%) than in CA-AD cases (5%; P<0.001). In conclusion, CA-SSA/P lesions exhibit a higher potential for lymphatic invasion and lymph node metastasis and have distinct histopathological features, including mucinous component, serrated architecture, tumour-infiltrating lymphocytes, Crohn-like inflammatory reaction, and absence of desmoplastic reaction, compared to their conventional counterparts.

Delineation of retroperitoneal metastatic lymph nodes in ovarian cancer with near-infrared fluorescence imaging.

Lymph node metastasis occurs in early-stage and late-stage ovarian cancers. Systematic lymphadenectomy is frequently conducted in an attempt to prevent disease progression. However, this method is associated with multiple complications. Therefore, it is necessary to develop a less invasive and more sensitive method for detecting lymphatic metastasis in ovarian cancer. The aim of the present study was to develop an appropriate fluorescent label for the analysis of lymphatic metastasis in vivo. To this end, epithelial ovarian cancer cells with high potential for lymph node metastasis were labeled using mCherry fluorescence. The cells were then imaged in vitro to determine the expression of mCherry, and in a mouse xenograft model in vivo. The data demonstrated the successful identification of metastatic retroperitoneal lymph nodes by co-localization with lymph nodes labeled by near-infrared fluorescence nanoparticles in vivo. These data provided important insights into the further development of methods for intra-operative identification of lymphatic metastasis and the mechanisms underlying lymphatic metastasis.

Clinicopathological implications to micropapillary bladder urothelial carcinoma of the presence of sialyl Lewis X-decorated mucin 1 in stroma-facing membranes

ObjectivesBladder urothelial carcinoma (UC) comprises more than 90% of all bladder cancers. Among several UC variants, micropapillary UC (MPUC) is a rare one with high potential for lymphovascular invasion and subsequent lymph node metastasis. Histologically, MPUC is characterized by the presence of small papillary carcinoma cell clusters surrounded by lacunar spaces. Immunohistochemically, the outer circumference of these clusters, that is, the stroma-facing membrane of carcinoma cells, is reportedly almost invariably positive for mucin 1 (MUC1) protein and to a lesser extent for sialyl Lewis X (sLeX) carbohydrates; however, the clinicopathological implications of these expression patterns have not been fully investigated. Materials and methodsWe performed immunohistochemical analysis of MPUC (n = 11) and conventional UC (n = 57) for MUC1 and sLeX to determine whether these factors immunolocalized. Dual immunofluorescence staining was also carried out to assess MUC1 and sLeX colocalization. We also performed Western blot analysis of Chinese hamster ovary cells misexpressing both recombinant epitope-tagged MUC1 and glycosyltransferases enabling sLeX biosynthesis. ResultsMPUC samples preferentially exhibited both MUC1 protein and sLeX carbohydrate expression on the stroma-facing membrane of carcinoma cells. Based on univariate analysis, MUC1 expression in that pattern was positively correlated with tumor extension, lymphovascular invasion, lymph node metastasis, disease stage, and relatively poor patient prognosis. A comparable sLeX expression pattern also correlated positively with tumor extension and nodal metastasis. Based on multivariate analysis, localization of MUC1 and sLeX on the stroma-facing side of the membrane was positively correlated with lymph node metastasis. ConclusionsOverall, our immunofluorescence findings as well as immunoprecipitation analyses of Chinese hamster ovary cell transfectants strongly suggest that MUC1 is a potential scaffold protein for sLeX carbohydrates in MPUC. Both MUC1 and sLeX may cooperatively contribute to MPUC histogenesis and clinicopathological characteristics.

Role of salvage lymph node dissection in prostate cancer.

Oligometastatic prostate cancer (PCA) has increasingly been detected in the era of modern imaging studies such as choline-specific and prostate-specific membrane antigen (PSMA)-positron emission tomography and X-ray computed tomography (PET/CT). Recent evidence suggests that durable control is attainable with local treatment modalities such as salvage metastasectomy or stereotactic radiation therapy targeting oligometastases, either with or without the use of systemic therapy. The purpose of this article is to critically review the current findings on the indication, extent, and oncologic outcome of salvage lymphadenectomy (SLAD). Oligometastatic PCA is defined by three or less to five metastatic lesions, no rapid spread to more sites, and feasibility of targeted treatment of all metastatic lesions with surgery or radiation therapy. Ga-PSMA-PET/CT or C-choline PET/CT represents the imaging study of choice to identify patients with potential lymph node metastases, and both studies should be performed at prostate-specific antigen serum levels around 1 ng/ml in order to achieve optimal results. If available, Ga-PSMA-PET/CT should be preferred because of higher sensitivity, specificity, and accuracy. With regard to pelvic SLAD, only data of retrospective studies with a total of more than 400 patients and an evidence level III-IV are available. SLAD should always be performed in terms of an extended lymph node dissection. Five-year biochemical-free survival ranges between 19 and 25%, 5-year cancer-specific survival varies between 75 and 90%. The median time to systemic treatment is in the range of 20-30 months. Patients with retroperitoneal metastases have a poorer prognosis with less than 10% responding. SLAD in oligometastatic PCA represents an individual approach with the major goal to prolong progression-free survival and time until systemic therapy is started. It is currently unclear whether SLAD will have an impact on long-term survival. Prospective randomized trials targeting this issue are on their way.

Clinicopathologic analysis of lymph node status in superficial esophageal squamous carcinoma.

BackgroundEndoscopic approaches are gradually considered as a reliable treatment of intramucosal esophageal squamous carcinoma. However, endoscopic resection (ER) is limited by the potential lymph node metastasis (LNM) at various depths of mucosal and submucosal invasion.MethodsWe conducted a retrospective review of 498 patients with pT1 superficial esophageal squamous carcinoma (SESC) who underwent surgical resection from January 2008 to August 2015. Pathological characteristics of tumors including location, size, appearance, differentiation, invasion depth, and nodal status were reviewed, and risk factors were analyzed.ResultsLNM was found in 0.0, 2.7, 6.3, 18.2, 15.9, and 34.3 % of the m1, m2, m3, sm1, sm2, and sm3 lesions, respectively. Univariate logistic regression identified the presence of the tumor size > 2 cm (p < 0.05), the presence of the poor tumor differentiation (p < 0.05), and the depth of tumor invasion (p < 0.05) and angiolymphatic invasion (p < 0.05) to be the important risk factors associated with the prevalence of tumor-positive lymph nodes. These findings were confirmed in multivariate logistic regression as independent predictors for LNM.ConclusionsER is considered as a reliable treatment of m1 to m2 lesions. Radical surgical resection (SR) is the standard and irreplaceable therapy of sm1 to sm3 lesions. Patients with m3 lesions should undergo ER as the initial procedure for diagnosis. And this treatment is supported only by a successful description of the tumor’s characteristics, including (1) only muscularis mucosa invasion and without invasion of the resection margins and (2) without any risk predictors for LNM. Otherwise, SR is recommended.

Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells with high lymph node metastasis potential preferentially via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) and E-cadherin.

Annexin A5 (Anxa5) is associated with the progression of some cancers, while its role and regulation mechanism in tumor lymphatic metastasis is rarely reported. This study aims to investigate the influence of Anxa5 knockdown on the malignant behaviours of murine hepatocarcinoma Hca-F cell line with high lymph node metastatic (LNM) potential and the underlying regulation mechanism. RNA interfering was performed to silence Anxa5 in Hca-F. Monoclonal shRNA-Anxa5- Hca-F cells were obtained via G418 screening by limited dilution method. Quantitative real-time RT-PCR (qRT-PCR) and Western blotting (WB) were applied to measure Anxa5 expression levels. CCK-8, Boyden transwell-chamber and in situ LN adhesion assays were performed to explore the effects of Anxa5 on the proliferation, migration, invasion and adhesion capacities of Hca-F. WB and qRT-PCR were used to detect the level changes of key molecules in corresponding signal pathways. We obtained two monoclonal shRNA-Anxa5-transfected Hca-F cell lines with stable knockdowns of Anxa5. Anxa5 knockdown resulted in significantly reduced proliferation, migration, invasion and in situ LN adhesion potentials of Hca-F in proportion to its knockdown extent. Anxa5 downregulation enhanced E-cadherin levels in Hca-F. Moreover, Anxa5 affected Hca-F behaviours specifically via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) instead of p38MAPK/c-Jun, Jnk/c-Jun and AKT/c-Jun pathways. Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells via ERK2/c-Jun/p-c-Jun(Ser73) and ERK2/E-cadherin pathways. It is an important molecule in metastasis (especially LNM) and a potential therapeutic target for hepatocarcinoma.

Salinomycin suppresses TGF-β1-induced epithelial-to-mesenchymal transition in MCF-7 human breast cancer cells

Epithelial-to-mesenchymal transition (EMT) is the major cause of breast cancer to initiate invasion and metastasis. Salinomycin (Sal) has been found as an effective chemical compound to kill breast cancer stem cells. However, the effect of Sal on invasion and metastasis of breast cancer is unclear. In the present study, we showed that Sal reversed transforming growth factor-β1 (TGF-β1) induced invasion and metastasis accompanied with down-regulation of MMP-2 by experiments on human breast cancer cell line MCF-7. Sal was able to inhibit TGF-β1-induced EMT phenotypic transition and the activation of key signaling molecules involved in Smad (p-Smad2/3,Snail1) and non-Smad (β-catenin, p-p38 MAPK) signals which cooperatively regulate the induction of EMT. Importantly, in a series of breast cancer specimens, we found strong correlation among E-cadherin expression, β-catenin expression, and the lymph node metastatic potential of breast cancer. Our research suggests that Sal is promised to be a chemotherapeutic drug by suppressing the metastasis of breast cancer.

ANXA5 level is linked to in vitro and in vivo tumor malignancy and lymphatic metastasis of murine hepatocarcinoma cell.

To investigate ANXA5 overexpression on in vitro and in vivo malignancies of murine Hca-P cells. Hca-P with low lymph node metastasis (LNM) potential was used as cell model. TEM, CCK-8 and Boyden transwell assays were performed for in vitro Hca-P behaviors. Hca-P-transplanted mouse model was established for in vivo experiment. ANXA5-overexpressing monoclonal Anxa5-Hca-P-1, Anxa5-Hca-P-2 and Anxa5-Hca-P-3 cells were obtained. ANXA5 upregulation alters the proliferation, morphology and rough endoplasmic reticulum of Hca-P cells, enhances in vitro migration and invasions of Hca-P, promotes in vivo malignant degree and LNM rate of Anxa5-Hca-P-3-transplanted mice. As a potential indicator for malignancy and lymphatic metastasis, ANXA5 overexpression increases in vitro migration and invasion of Hca-P cell, promotes in vivo malignancy, LNM rate and level of Hca-P-transplanted mice.

Une localisation parotidienne bilatérale d’un carcinome épithélial myoépithélial

We report the case of a 52-year-old man, who was admitted in the department of otorhinolaryngology for a mass of the right parotid gland. The radiological and clinical hypothesis was a squamous cell carcinoma. Histopathological examination revealed a biphasic proliferation composed of epithelial cells arranged in a tubular pattern stained with cytokeratins 5-6 and 7 and EMA surrounded by clear myoepithelial cells stained with smooth muscle actin and p63. Ki-67 labeling index was low. The diagnosis of epithelial myoepithelial carcinoma was proposed. One year after, the patient noticed a centimetric mass of the left parotid gland. The radiological hypothesis was the presence of an intraparotidian lymph node. Histopathological examination showed a second epithelial myoepithelial carcinoma. This is an uncommon neoplasm comprising approximately 1% of all salivary gland tumours, affecting mainly the parotid gland. It is occurring preferably in patients older than 60years old. This is a low-grade malignant tumour with tendency to local recurrence and lymph node metastatic potential. We describe an exceptional bilateral epithelial myoepithelial carcinoma of the parotid gland.

Image‐guided surgery using multimodality strategy and molecular probes

The ultimate goal of cancer surgery is to maximize the excision of tumorous tissue with minimal damage to the collateral normal tissues, reduce the postoperative recurrence, and improve the survival rate of patients. In order to locate tumor lesions, highlight tumor margins, visualize residual disease in the surgical wound, and map potential lymph node metastasis, various imaging techniques and molecular probes have been investigated to assist surgeons to perform more complete tumor resection. Combining imaging techniques with molecular probes is particularly promising as a new approach for image-guided surgery. Considering inherent limitations of different imaging techniques and insufficient sensitivity of nonspecific molecular probes, image-guided surgery with multimodality strategy and specific molecular probes appears to be an optimal choice. In this article, we briefly describe typical imaging techniques and molecular probes followed by a focused review on the current progress of multimodal image-guided surgery with specific molecular navigation. We also discuss optimal strategy that covers all stages of image-guided surgery including preoperative scanning of tumors, intraoperative inspection of surgical bed and postoperative care of patients.

Identification of lymphatic metastasis-associated genes in a metastatic ovarian cancer cell line.

Ovarian cancer (OC) is the gynecological malignancy with the highest rate of mortality, and lymphatic metastasis is a critical factor in disease recurrence and prognosis. In the current study, the SKOV-3/LN403 cell line, which has high potential for lymph node metastasis was established as a result of four rounds of selection from retroperitoneal lymph nodes following intraperitoneal injections of SKOV-3 ovarian adenocarcinoma cells. In comparison to the parental SKOV-3 cell line, SKOV-3/LN403 has a higher rate of proliferation, is more invasive and exhibits greater resistance to paclitaxel. Subsequently, a novel animal model of OC lymphatic metastasis was developed with SKOV-3/LN403 cells and a high incidence of positive metastatic lymph nodes, peritoneal dissemination and bloody ascites were observed, which mimicked the clinical outcome of patients with OC. Analysis of the gene expression profiles of SKOV-3 and SKOV-3/LN403 cells identified several genes and pathways that may be involved in lymphatic metastasis of OC. The induction of focal adhesion kinase expression provides a potential therapeutic target for OC lymphatic metastasis.

Loss of Leucine Zipper Putative Tumor Suppressor 1 (LZTS1) Expression Contributes to Lymph Node Metastasis of Breast Invasive Micropapillary Carcinoma

Breast invasive micropapillary carcinoma (IMPC) is a rare subtype of breast cancer with a high potential of lymph node metastasis, aggressive clinical behavior, and poor disease-free or overall survival. Expression of leucine zipper putative tumor suppressor 1 (LZTS1) was frequently lost or reduced in breast cancer tissues. This study investigated the expression of LZTS1 protein in breast IMPC tissues using immunohistochemistry. In addition, somatic LZTS1 mutations and promoter methylation were assessed to determine an association with clinicopathological data from IMPC patients. LZTS1 protein was downregulated in 62 (62 %) of 100 IMPC tissue samples and was significantly associated with lymph node metastasis (P < 0.05). A LZTS1 exon mutation occurred in one of the 53 IMPC cases analyzed, whereas a LZTS1 intron mutation occurred in 26 of 53 cases. Moreover, LZTS1 promoter was frequently methylated in IMPC samples and was associated with reduced LZTS1 expression levels in IMPC tissues. These data demonstrated that the loss of LZTS1 expression was associated with lymph node metastasis in patients with IMPC, and LZTS1 promoter methylation could be responsible for the loss of LZTS1 expression.

Diagnostic accuracy of multi detector-row computed tomography (MDCT) and endoscopic ultrasound (EUS) for clinical N staging in early gastric cancer.

17 Background: An accurate preoperative assessment of potential lymph node metastasis is useful in the decision for the treatment strategy of early gastric cancer. The aim of this study was to retrospectively evaluate the accuracy of preoperative assessment of lymph node status with multi detector-row computed tomography (MDCT) and endoscopic ultrasound (EUS). Methods: We had analyzed 1,104 patients with early gastric cancer who underwent gastrectomy with lymph-node dissection at Seoul National University Bundang Hospital from May 2003 to July 2011. Patients were underwent preoperative MDCT in 1,104 and EUS in 1,028. Lymph nodes were considered positive for metastasis if they were larger than 8mm in the short axis diameter of MDCT. The criteria of EUS for metastatic lymph nodes are rounded nodes larger than 8 mm diameter with hypoechogenicity. The clinical N staging of preoperative MDCT and EUS was compared to the postoperative pathological finding. Results: The overall diagnostic accuracy of MDCT and EUS for determining lymph node metastasis was 89.1% and 90.5%. In MDCT, the rate of overestimation of lymph node metastasis was 8.20% (91/1104) and underestimation was 8.7% (96/1104). Tumor size (&gt;2cm) was significant related with overestimation (p=0.007). Underestimation of clinical N staging was related with female (p=0.025, OR 2.025), lymphovascular invasion (p&lt;0.0001, OR 7.807), positive EGFR (p=0.015, OR 2.566) and tumor size (&gt;2cm) (p=0.009, OR 3.221). In EUS, overestimated lymph node metastasis was 5.40% (56/1028) and underestimation was 9.6% (99/1028). No factor was significantly related with overestimation. Underestimation of lymph node metastasis was related with female (p=0.020, OR 2.049), lymphovascular invasion (p&lt;0.0001, OR 11.716), positive EGFR (p=0.024, OR 2.489) and tumor size (&gt;2cm) (p=0.020, OR 2.774). Conclusions: For preoperative assessment of lymph node metastasis in early gastric cancer, MDCT and EUS showed high diagnostic accuracy. Both MDCT and EUS, female, lymphovascular invasion, positive EGFR, large tumor size (&gt;2cm) were related to underestimation of clinical N staging. We proposed that careful attention is required to choose treatment based on clinical N staging by MDCT and EUS.

Annexin A11 knockdown inhibits in vitro proliferation and enhances survival of Hca-F cell via Akt2/FoxO1 pathway and MMP-9 expression

Annexin A11 (Anxa11), a Ca2+-regulated phospholipid-binding protein, is involved in cell apoptosis, differentiation, vesicle trafficking, cancer progression and autoimmune diseases. Previous study from our group indicated that Anxa11 was associated with lymphatic metastatic potential of murine hepatocarcinoma cells. Herein, we investigated the effects and action mechanism of Anxa11 knockdown on in vitro cell proliferation and apoptosis of Hca-F, a murine hepatocarcinoma cell with∼75% lymph node metastatic potential. Real-time PCR and western blotting assays indicated that Anxa11 was significantly downregulated in monoclonal Anxa11-shRNA-transfected Hca-F cells. Anxa11 knockdown in Hca-F suppressed its in vitro proliferation and cell apoptosis capacities. Following Anxa11 knockdown in Hca-F cells, Bax/Bcl-2 expression level ratio, Akt2 and FoxO1 (pSer319) expression levels as well as MMP-9 mRNA and active MMP-9 protein levels were significantly elevated in Hca-F cells. In conclusion, Annexin A11 knockdown inhibits the in vitro proliferation and cell apoptosis of Hca-F cell via Akt2/FoxO1 and/or MMP-9 expression pathway. Anxa11 might play an important role in hepatocarcinoma cell invasion and metastasis and hepatocarcinoma malignancy.

Supraclavicular Lymphadenopathy: Should It Be Perceived as the Virchow's Node of Head and Neck Tumors?

Background: In this study, we aimed to determine the correlation between supraclavicular lymph node involvement (SLNI) and metastatic potential, frequency, and metastases predilection sites in patients diagnosed with various head and neck tumors (HNT) and staged via positron emission tomography/computed tomography (PET/CT) imaging. We also investigated the impact of different variables on SLNI. Patients and Methods: 270 patients diagnosed with HNT were enrolled in the study (194 males and 96 females, mean age 54.9 ± 14.7 years (range 18-89 years)). Results: Nasopharyngeal carcinoma demonstrated significant SLNI (p < 0.01); however, other subtypes of HNT did not. In all HNT studied, no apparent metastatic predilection tendency for the supraclavicular region was observed, as opposed to the well-described Virchow's node. Age, gender, tumor size, and systemic metastases were not identified as statistically significant variables contributing to SLNI. Multivariate regression analysis revealed an increased cervical (p < 0.01) and thoracic (p = 0.001) lymph node involvement in patients with SLNI. Conclusion: SLNI with the possibility of metastasis was more frequently observed in nasopharyngeal carcinoma, advancing the nodal status without significantly influencing the T and M stages. A careful evaluation of this very small region is of critical importance for proper nodal staging in nasopharyngeal cancer patients.

CRKL overexpression suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cells

The signal adaptor CRK family protein play important roles in cancer cell progression, proliferation, migration and invasion. Previously, we showed that CRK was involved in lymphatic metastatic potential of murine hepatocarcinoma cells. In current work, as a member of CRK family, chicken tumour virus number 10 regulator of kinase-like protein (CRKL) was revealed to be associated with malignant behaviors of Hca-P, a murine HCC cell with lymph node metastatic (LNM) rate of ∼25%. CRKL overexpression in Hca-P by a constructed eukaryotic expression vector of pcDNA3.1/V5-HisB-CRKL significantly ameliorated its malignant biological properties. CCK-8 and soft agar colony formation assays indicated CRKL overexpression significantly inhibits the cell proliferation and colony formation abilities of Hca-P. Additionally, transwell assays indicated that the Hca-P cell migration and invasion capacities were apparently reduced following CRKL overexpression. As Hca-P is an ideal hepatocarcinoma cell model with low (initial) LNM potential, CRKL is shown to act as a potential suppressor and to provide new insight for both the malignant behaviors of hepatocarcinoma cells and lymphatic metastasis mechanism of hepatocarcinoma.