Positive Lymph Node Invasion Research Articles

Radical cystectomy for bladder urothelial carcinoma with aggressive variant histology.

The aim of this study is to report our experience in managing bladder cancer in patients with variant pathology. Retrospective data collection for all patients managed by radical cystectomy over the last 3 years for a variant pathol-ogy was completed. We specifically included micropapillary and nested variants. Ten patients were identified, with eight having micropapillary carcinoma (MPC) and two having nested vari-ants. Nine patients were male. The median age was 75. The two patients with nested variant were 56 and 62 years old, respec-tively, whereas all patients with MPC were over the age of 70. Upon cystectomy of all micropapillary cases, three patients (37.5%) had positive lymph node invasion and the final patholo-gy was T2 (two patients), T3 (two patients), and T4 (four patients). Barring a grade III complication Clavien-Dindo classi-fication due to wound dehiscence that necessitated secondary surgical closure, there were no specific perioperative complica-tions. Given the urethral invasion, cystourethrectomy was per-formed on the female patient. Within a median 13-month fol-low-up, three patients developed local recurrence, including two urethral and one new lateral pelvic mass. Considering the muscle invasive nature of micropapillary and nested bladder cancer, aggressive surgical management should not be postponed. Moreover, due to notable prevalence of concurrent and/or recurrent urethral involvement, initial urethrectomy or early and frequent postoperative ure-throscopy should be provided. Patients with variant histology bladder cancer may benefit from early radical cystectomy when compared to bladder sparing protocols and prostate sparing cystectomy treatment options.

Circular RNA circ_0001287 inhibits the proliferation, metastasis, and radiosensitivity of non-small cell lung cancer cells by sponging microRNA miR-21 and up-regulating phosphatase and tensin homolog expression

ABSTRACT As a type of non-coding RNA, circular RNA (circRNA) figures prominently in human cancer progression. Nonetheless, the expression, function, and regulatory mechanism of circ_0001287 in non-small cell lung cancer (NSCLC) remain obscure. In this work, quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to quantify circ_0001287 and miR-21 expressions in NSCLC tissues and cells. The relationship between circ_0001287 expression and the clinicopathological parameters of NSCLC patients was examined. Cell counting kit-8 (CCK-8), 5-bromo-2©-deoxyuridine (BrdU), and Transwell experiments were conducted to detect the multiplication, migration, and invasion of NSCLC cells after circ_0001287 was overexpressed or knocked down. The survival of NSCLC cells was studied using colony formation experiment under different doses of radiation. RNA immunoprecipitation (RIP) experiment and luciferase reporter gene experiment verified the binding relationship between circ_0001287 and miR-21. Western blot was employed to examine the regulatory effects of circ_0001287 and miR-21 on phosphatase and tensin homolog (PTEN) expression. We reported that circ_0001287 expression was down-modulated in NSCLC tissues and cell lines. Besides, circ_0001287 low expression was associated with low differentiation and positive lymph node invasion of NSCLC. Circ_0001287 overexpression suppressed the multiplication, migration, invasion, and radioresistance of NSCLC cells, whereas circ_0001287 knockdown promoted the above phenotypes. Circ_0001287 could adsorb miR-21 and repress its expression, and indirectly up-modulate PTEN expression in NSCLC cells. Taken together, circ_0001287/miR-21/PTEN axis is probably involved in regulating NSCLC cell multiplication, metastasis, and radioresistance.

The efficiency of collagen III, metalloproteinase 1, carcinoembryonic antigen, and carbohydrate antigen 19.9 for colon cancer diagnosis

Background: Currently, blood markers are noninvasive methods for the diagnosis of patients with colorectal cancer (CRC). We evaluated four biomarkers (Carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA19.9), collagen III, and metalloproteinase 1 (MMP-1)) and their combination as a substitute method to enhance diagnosis of CRC. Subjects and methods: one hundred ninety-five patients who had undergone colonoscopy examination were included in the study (135 CRC and 60 benign growths). Also, 45 healthy individuals were included. Multivariate discriminant analysis (MDA) and area under the receiver operating characteristic curve (AUC) were applied for evaluating the diagnostic power of single and their combination. Results: levels of collagen III, CEA, and CA 19.9 increased while MMP-1 decreased with the progression of CRC (stages, positive lymph node invasion, distant organ metastasis, and high grades) with a significant difference (P P < 0.0001). Combination of MMP-1, CEA, CA 19-9, and Collagen III yielded MC3 index had diagnostic power greater than every single marker could achieve alone. When differentiating colon cancer from benign growth, the AUC of MC3 index was 0.91 yielded 85.2% sensitivity and 86.7% specificity. Moreover, the MC3 index for patients with late stages, lymph node invasion, organ metastasis, and high-grade had AUC = 0.81, 0.82, 0.80, and 0.80 higher than CEA and CA19.9.Conclusion: MC3 index is can be used as an effective index for early detection of CRC.

Elevation of circular RNA circ_0003645 forecasts unfavorable prognosis and facilitates cell progression via miR-1179/TMEM14A pathway in non-small cell lung cancer

BackgroundNon-small cell lung cancer (NSCLC) is a highly aggressive malignancy with increasing incidence across the world. The role and mechanism of circular RNAs (circRNAs) in the pathogenesis of NSCLC have not been understood exactly. In this work, we aims to explore a novel NSCLC-associated circRNA, circ_0003645. MethodsThe expression profile of circ_0003645 was evaluated in NSCLC tissue specimens and cells. Additionally, the correlation between circ_0003645 and clinical features/patients’ prognosis were investigated. Functionally, CCK-8, clone formation, flow cyometric and transwell assays were performed in two cell lines. Furthermore, dual-luciferase reporter and rescue experiments were carried out to elucidate the mechanism of circ_0003645. ResultsThe data demonstrated an upregulation of circ_0003645 in patients’ tissue specimens and cells. Overexpression of circ_0003645 in tissues was related to advanced TNM stages, positive lymph node invasion and unfavorable prognosis for the patients with NSCLC. In addition, gain and loss of function assays uncovered that circ_0003645 functioned as an oncogene in NSCLC cells. Moreover, circ_0003645 acted as a ceRNA to sponge miR-1179, which resulted in the elevation of TMEM14A expression and facilitated cell progression. Conclusions: This study indicates that circ_0003645 might possess crucial potential as a prognosis predictor and therapeutic target for NSCLC patients.

Upregulated circular RNA circ_0030235 predicts unfavorable prognosis in pancreatic ductal adenocarcinoma and facilitates cell progression by sponging miR-1253 and miR-1294

Accumulating evidence indicated that dysregulated circular RNAs (circRNAs) could play pivotal roles in cancer biology. A recent study demonstrated that circ_0030235 expression is upregulated in human pancreatic ductal adenocarcinoma (PDAC) by high-throughput circRNA microarray. In the current work, we aimed to elucidate the clinical significance, prognostic value, functional roles and mechanism of circ_0030235 in PDAC. Quantitative real time-PCR was used to detect circ_0030235 expression in PDAC tissue specimens and cell lines. The clinical significance of circ_0030235 was evaluated by Fisher's exact test, Kaplan-Meier curves, and Cox regression analysis. Cell growth, apoptosis, and metastatic properties were then explored after circ_0030235 knockdown/overexpression. Dual luciferase reporter assay was applied to detect the mechanisms of circ_0030235. As a result, the data documented that circ_0030235 was upregulated in PDAC cell lines and cancerous tissues compared with HPDE and matched normal tissue specimens, respectively. Overexpression of circ_0030235 in tumor samples is related to higher tumor stage and positive lymph node invasion. Additionally, analyses documented that high expression of circ_0030235 was associated with poor prognosis for PDAC patients. Knockdown of circ_0030235 by siRNAs inhibited cell growth, migratory and invasive potential, and promoted cell apoptosis. On the contrary, overexpression of circ_0030235 caused the opposite effect. Mechanistically, circ_0030235 directly sponges miR-1253 and miR-1294 in PDAC cells. What's more, the oncogenic properties of circ_0030235 was partly dependent on its suppression on miR-1253 and miR-1294. Overall, the results showed that circ_0030235 might act as an effective therapeutic target and indicate dismal prognosis for PDAC.

Upregulated circular RNA circ_0007534 indicates an unfavorable prognosis in pancreatic ductal adenocarcinoma and regulates cell proliferation, apoptosis, and invasion by sponging miR-625 and miR-892b.

Circular RNAs (circRNAs) have been regarded as critical regulators of human diseases and biological markers in some types of malignancies, including pancreatic ductal adenocarcinoma (PDAC). Recently, circ_0007534 has been identified as a novel cancer-related circRNA. Nevertheless, its clinical relevance, functional roles,and mechanism have not been studied in PDAC. In the current study, real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of circ_0007534 in 60-paired PDAC tissue samples and different cell lines. Loss-of-function and gain-of-function assays were performed to detect cell proliferation, apoptosis, and metastatic properties affected by circ_0007534. Ananimal study was also carried out. The luciferase reporter assay was performed to uncover the underlying mechanism of circ_0007534. As a result, circ_0007534 was overexpressed not only in PDAC tissues but also in a panel of PDAC cell lines, and this overexpression is closely associated with advanced tumor stage and positive lymph node invasion. In addition, circ_0007534 may be regarded as an independent prognostic factor for patients with PDAC. For the part of functional assays, circ_0007534 significantly increased cell proliferation, migratory, and invasive potential of PDAC cells. Circ_0007534 could inhibit cell apoptosis partly via aBcl-2/caspase-3 pathway. The xenograft study further confirmed the cell growth promoting therole of circ_0007534. Mechanistically, miR-625 and miR-892b were sponged by circ_0007534. The oncogenic functions of circ_0007534 is partly dependent on its regulation of miR-625 and miR-892b. In conclusion, our study illuminates a novel circRNA that confers an oncogenic function in PDAC.

Expression of orphan GPR56 correlates with tumor progression in human epithelial ovarian cancer.

G protein-coupled receptor 56 (GPR56) has been demonstrated to be a significant prognostic predictor in several types of malignances, including melanoma, glioblastoma, breast cancer, colon cancer, and pancreatic cancer. GPR56 has a putative mucin-like extracellular domain, indicating functions for this receptor in the cell-cell interactions and triggering different downstream signaling pathways responsible for regulating cell survival, proliferation, adhesion, and migration. But the expression and clinical significance of GPR56 has not been elucidated in epithelial ovarian cancer (EOC). We detected GPR56 expression by immunohistochemistry in 110 samples of ovarian serous carcinoma to explore the correlation between its expression and clinicopathologic characteristics and overall survival. As the result, we found that GPR56 expression is significantly associated with advanced FIGO stage (P = 0.01) and positive lymph node invasion (P = 0.016), and it serves as an independent unfavorable prognostic factor through univariate and multivariate analysis. GPR56 knockdown could dramatically decrease the proliferation and invasion of epithelial ovarian cancer cells through down-regulating the RhoA-GTP level and up-regulating the E-cadherin level, which indicates GPR56 could promote the progression and invasion of EOC. In conclusion, GPR56 expression was demonstrated as an independent prognostic factor in EOC, suggesting that GPR56 may play an oncogenic role through the Rho and E-cadherin pathway and GPR56 could be a novel potential drug target in EOC.

Validity of 18F-fluorodeoxyglucose positron emission tomography/computed tomography for pretreatment evaluation of patients with cervical carcinoma: a retrospective pathology-matched study.

The aim of this study was to evaluate the validity of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for pretreatment evaluation of patients with cervical carcinoma. Retrospective evaluation of 63 patients, diagnosed with stage IA-IIA cervical carcinoma who underwent 18F-FDG PET/CT before surgery, was performed. Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios (LRs) of PET/CT for predicting the positive cervix, vagina, uterine body, and lymph node invasion at the surgical specimen was calculated. Sensitivity, specificity, positive predictive value, and negative predictive value of the positive cervix invasion in PET/CT to detect positive surgical specimen were 88.2%, 75%, 93.8%, and 60%, respectively. The LR+ ratio was 3.5, and the LR- ratio was 0.2. Sensitivity, specificity, positive predictive value, and negative predictive value of the positive vagina invasion in PET/CT to detect positive surgical specimen were 100%, 70.97%, 5.3%, and 100%, respectively. The LR+ ratio was 3.4, and the LR- ratio was 0. Sensitivity, specificity, positive predictive value, and negative predictive value of the positive uterine body invasion in PET/CT to detect positive surgical specimen were 75%, 83.1%, 23.1%, and 98%, respectively. The LR+ ratio was 4.4, and the LR- ratio was 0.3. Sensitivity, specificity, positive predictive value, and negative predictive value of the positive lymph node invasion in PET/CT to detect positive surgical specimen were 87.5%, 78.4%, 38.9%, and 97.6%, respectively. The LR+ ratio was 4.1, and the LR- ratio was 0.2. The cervix invasion, negative uterine body invasion, and negative lymph node invasion are effective 18F-FDG PET/CT findings.

Abstract 4727: Prognostic roles of DDB2 and XPC mRNA expressions in treatment responses and overall survivals of head and neck cancer patients

Abstract Background: DNA repair genes function in the maintenance of genome integrity and prevent tumorigenesis. On another hand, DNA repair genes modulate cancer cell responses to DNA-damaging therapeutics. We hypothesize that altered expression of DNA repair genes are correlated with therapeutic outcomes of head and neck cancer patients. Patients and methods: Messenger RNA (mRNA) expressions of DDB2 and XPC were examined in specimens of 95 head and neck cancer patients using real-time quantitative RT-PCR. Patients were dichotomized by ROC curve analysis based on their DDB2 and XPC mRNA levels. Overall survival (OS) rates were measured using Kaplan-Meier estimates and the log-rank tests. The adjusted hazard rate ratios (HRRs) were computed by multivariate Cox regressions. Results: The levels of DDB2 and XPC mRNA expression in tumor tissues were reduced (tumor/normal &amp;lt; 0.9) in 84 and 80 cases, respectively, when compared with those in adjacent normal parts. Lower DDB2 (tumor/normal &amp;lt; 0.24) and XPC (tumor/normal &amp;lt; 0.36) mRNA expressions were correlated with larger tumor, positive lymph node invasion, advanced stage, and poor 5-yr OS rates (26.7% vs. 54.3%, and 28.1% vs. 53.0%, respectively). Multivariate Cox model showed that, in addition to T and N stages, lower XPC mRNA level (&amp;lt; 0.36) was an independent risk factor for patient's survival (HRR = 2.68, 95% CI 1.12-6.40). Concurrent chemotherapy and radiotherapy (CCRT) did not improve OS of patients with lower XPC mRNA (&amp;lt; 0.36) and showed even worse outcomes within 5 years for patients with lower DDB2 expression (&amp;lt; 0.24). However, patients with higher DDB2 (&amp;gt; 0.24) and XPC (&amp;gt; 0.36) mRNA levels had improved 5-yr OS rates if they received CCRT (64.4% vs. 41.8% and 73.3% vs. 39.2%). Conclusion: mRNA expressions of XPC and DDB2 might be useful biomarkers for prognosis and efficacy of CCRT medication in head and neck cancer patients. Citation Format: Chang-Shen Lin, Ka-Wo Lee, Jau-Ling Huang, Yu-Chu Wang, Yi-Shan Tsai. Prognostic roles of DDB2 and XPC mRNA expressions in treatment responses and overall survivals of head and neck cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4727. doi:10.1158/1538-7445.AM2014-4727

Linfadenectomía extendida pélvica bilateral en cáncer de pene. Aspectos técnicos

The most important prognostic factor in cancer of the penis is the presence of lymph node metastases and they are detected in 28 % to 64 % of the cases. Lymphadenectomy is curative in 75 % of the patients presenting with one or 2 positive lymph nodes and in 20 % of the patients with pelvic invasion. Thus it is the most effective treatment for eradicating lymph node metastases in selected patients.A 49-year-old man presented with an indurated, exophytic, 3.5cm vegetative tumor in the glans penis and a right inguinal increase in volume. A biopsy was taken that reported invasive squamous cell carcinoma. Partial phallectomy and bilateral extended superficial inguinal lymphadenectomy were performed. The histopathologic study reported moderately differentiated squamous cell carcinoma measuring 3.7cm that affected the corpus spongiosum, and disease-free margins. There was positive lymph node invasion; 8 right inguinal lymph nodes were found, one of which was positive and 5 left inguinal lymph nodes were identified, one of which was positive.Laparoscopic bilateral extended lymphadenectomy was performed, with 2 positive right obturator lymph nodes.Cancer of the penis is a disease with an unfavorable outcome. Surgery is essential for attempting to cure the patient with lymph node invasion and it improves outcome, reaching a 5-year survival rate above 60 %; in the cases of pelvic lymph node invasion that rate is 20 %. The laparoscopic approach has advantages in relation to morbidity and pain control, as well as an adequate oncologic result.

Histological features of extratumoral breast lesions as a predictive factor of familial breast cancer

The aim of this study was to verify whether histopathological features of extratumoral and of primary tumor breast tissue could play a role in identifying patients with familial characteristics. We examined the clinicopathological features of 504 patients with sporadic or familial breast cancer stratified for risk of BRCA mutation. Patients with a higher risk of being carrier of BRCA gene mutations were significantly associated with tumor poor differentiation (p=0.003), positive lymph node invasion (p=0.02) and presence of vascular peritumoral invasion (p=0.008). Among the extra-tumoral lesions, only the epithelial proliferative lesions were related to higher mutation risk both in the overall series and familial patients (p<0.0001 and p=0.003, respectively). Interestingly, a significant difference in terms of high mutation risk was observed in usual ductal hyperplasia lesions (UDH), (p=0.002). We suggest that vascular peritumoral invasion and UDH lesions could predict a higher mutation risk of BRCA1 and BRCA2 genes and help in individuating patient candidates to further molecular analysis.