Nuclear localization of NF-kappaB p65 in primary prostate tumors is predictive of pelvic lymph node metastases

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10077-10077
Author(s):  
L. Lessard ◽  
P. Bellon-Gagnon ◽  
M. Alam-Fahmy ◽  
P. Karakiewicz ◽  
A. Mes-Masson ◽  
...  

10077 Background: Pelvic lymph node metastases are associated with a greater risk of prostate cancer recurrence and peripheral metastasis. Unfortunately, markers predictive of lymph node metastasis and/or recurrence after radical prostatectomy are limited and new molecular markers are needed to identify patients at higher risk of progression. NF-kB (p65) is a candidate molecular marker already associated with poor clinical outcomes such as biochemical recurrence and bone metastasis. We have also reported elevated nuclear p65 expression in prostate cancer lymph node metastasis. Pertinent to this issue, we tested whether the nuclear localization of p65 in radical prostatectomy specimens could predict the presence of lymph node metastases. Methods: Following informed consent, 51 patients who underwent radical prostatectomy were included in the study: 20 patients had lymph node metastasis at surgery and 31 patients had no evidence of lymph node metastasis and were used as the control group. All cases in the control group had no biochemical relapse 5 years following radical prostatectomy. NF-kB expression in prostate tumor sections was assessed by immunohistochemistry using a monoclonal NF-kB p65 antibody. The relation between nuclear p65 expression in primary tumors and lymph node metastasis was tested in univariate and multivariate Cox regression models. Results: Primary tumors of metastatic patients had an average of 21.25% of tumor cells with nuclear p65 expression as opposed to 9.42% of tumor cells of control patients (p=0.001). Univariate Cox regression demonstrated a 7.5% increased risk of having lymph node metastases for each percent increase in p65 nuclear staining (p=0.003). In the multivariate model, after controlling for pre-operative PSA (p=0.175), Gleason patterns (p=0.382), pathological stage (p=0.436), extracapsular extension (p=0.243) and seminal vesicle invasion (p=0.016), nuclear p65 was associated with an 8.8% increased risk for lymph node metastases (p=0.024). Conclusion: In univariate and multivariate analyses, p65 nuclear expression was strongly predictive of lymph node invasion. We propose that nuclear NF-kB (p65) may serve as a useful independent molecular marker for stratifying patients at risk for lymph node metastases. No significant financial relationships to disclose.

2003 ◽  
Vol 90 (10) ◽  
pp. 591-597 ◽  
Author(s):  
Riccardo Nisato ◽  
Jean-Christophe Tille ◽  
Michael Pepper

SummaryIn several human cancers, increased expression in primary tumors of vascular endothelial growth factor-C (VEGF-C) is correlated with regional lymph node metastasis. Studies using transgenic mice overexpressing VEGF-C, or xenotransplantation of VEGF-C-expressing tumor cells into immunodeficient mice, have demonstrated a role for VEGF-C in tumor lymphangiogenesis and the subsequent formation of lymph node metastasis. However, at variance with data obtained in animal models, there is at present very little evidence for lymphangiogenesis in human tumors. Nonetheless, the striking correlation between levels of VEGF-C in primary human tumors and lymph node metastases exists, which suggests that VEGF-C may serve functions other than lymphangiogenesis. Thus, VEGF-C may activate pre-existing lymphatics which in turn become directly involved in tumor cell chemotaxis, intralymphatic intravasation and distal dissemination. A reciprocal dialogue is therefore likely to exist between tumor and lymphatic endothelial cells which results in the formation of lymph node metastases.This publication was partially financed by Serono Foundation for the Advancement of Medical Science.Part of this paper was originally presented at the 2nd International Workshop on New Therapeutic Targets in Vascular Biology from February 6-9, 2003 in Geneva, Switzerland.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 965
Author(s):  
Selina Hiss ◽  
Markus Eckstein ◽  
Patricia Segschneider ◽  
Konstantinos Mantsopoulos ◽  
Heinrich Iro ◽  
...  

Objectives: The aim of this study was to assess the number of tumour-infiltrating lymphocytes (TILs) and the expression of Programmed Cell Death 1 Ligand 1 (PD-L1) in Acinic Cell Carcinoma (AciCC) of the salivary glands, to enable a correlation with clinico-pathological features and to analyse their prognostic impact. Methods: This single centre retrospective study represents a cohort of 36 primary AciCCs with long-term clinical follow-up. Immunohistochemically defined immune cell subtypes, i.e., those expressing T-cell markers (CD3, CD4 and CD8) or a B-cell marker (CD20) were characterized on tumour tissue sections. The number of TILs was quantitatively evaluated using software for digital bioimage analysis (QuPath). PD-L1 expression on the tumour cells and on immune cells was assessed immunohistochemically employing established scoring criteria: tumour proportion score (TPS), Ventana immune cell score (IC-Score) and combined positive score (CPS). Results: Higher numbers of tumour-infiltrating T- and B- lymphocytes were significantly associated with high-grade transformation. Furthermore, higher counts of T-lymphocytes correlated with node-positive disease. There was a significant correlation between higher levels of PD-L1 expression and lymph node metastases as well as the occurrence of high-grade transformation. Moreover, PD-L1 CPS was associated with poor prognosis regarding metastasis-free survival (p = 0.049). Conclusions: The current study is the first to demonstrate an association between PD-L1 expression and lymph node metastases as well as grading in AciCCs. In conclusion, increased immune cell infiltration of T and B cells as well as higher levels of PD-L1 expression in AciCC in association with high-grade transformation, lymph node metastasis and unfavourable prognosis suggests a relevant interaction between tumour cells and immune cell infiltrates in a subset of AciCCs, and might represent a rationale for immune checkpoint inhibition.


2001 ◽  
Vol 125 (7) ◽  
pp. 921-923 ◽  
Author(s):  
Jiazhong Jiang ◽  
Thomas M. Ulbright ◽  
Cheryl Younger ◽  
Katya Sanchez ◽  
David G. Bostwick ◽  
...  

Abstract Background.—Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are 2 types of intermediate filament protein. Expression of CK7 is seen in the majority of primary urinary bladder carcinomas. CK20 is restricted to superficial and occasional intermediate cells of the normal urothelium of the bladder. Aberrant CK20 expression has been documented in urothelial carcinoma and has proved useful as an ancillary diagnostic aid for urinary bladder tumor. Our hypothesis is that the pattern of CK7 and CK20 expression in metastatic urothelial carcinoma duplicates the expression of the same markers in the primary tumors. Therefore, immunohistochemical staining of metastatic tumors for these 2 markers may be helpful for differential diagnosis in ambiguous metastatic tumor deposits. Objective.—To determine the concordance of CK7 and CK20 expression in primary bladder urothelial carcinoma and the matched lymph node metastasis. Design.—We studied 26 patients with lymph node metastases who underwent radical cystectomy and bilateral lymphadenectomy for bladder carcinoma. Immunohistochemical staining for CK7 and CK20 was performed on formalin-fixed paraffin-embedded tissues containing primary cancers and lymph node metastases. Results.—In all cases, there was a concordant expression of CK20 in the primary cancer and its matched lymph node metastasis. Twelve cases (46%) showed positive CK20 immunoreactivity in the primary tumor and its matched lymph node metastases, whereas 14 cases (54%) were negative for CK20 in both the primary tumor and lymph node metastasis. All cases showed positive CK7 immunoreactivity in the primary cancers and matched lymph node metastases. Conclusions.—CK20 immunoreactivity is reliably observed in metastases from bladder cancer when the primary tumor expresses CK20.


2014 ◽  
Vol 8 (7-8) ◽  
pp. 554 ◽  
Author(s):  
Nuri Yigit ◽  
Yildirim Karslioglu ◽  
Bulent Kurt

A radical prostatectomy affects the prostate, bilateral seminal vesicles (SV), and the distal parts of the bilateral vasa deferentia (VD). SV invasion (SVI) is associated with an increased risk of lymph node metastasis and recurrence. However, the significance of VD invasion (VDI), either with or without the involvement of their surgical margins, has not been fully appreciated. We think VDI might have an independent prognostic significance, as does SVI, and should be incorporated into the pathology guidelines and the staging systems of prostatic adenocarcinoma. Our case illustrates this.


2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Caitlin Harrington ◽  
Rebecca Carr ◽  
Smita Sihag ◽  
Prasad Adusumilli ◽  
Manjit Bains ◽  
...  

Abstract   Although the pattern of nodal metastasis and the prognosis of number and location of positive nodes have been well described with esophageal cancer undergoing upfront surgery, little is known about nodal metastasis after neoadjuvant treatment. The aim of this study is to assess the pattern of nodal metastases in esophageal adenocarcinoma treated with neoadjuvant chemoradiation and surgery and evaluate its effect on prognosis. Methods All patients with esophageal adenocarcinoma who had undergone neoadjuvant chemoradiation and an R0 esophagectomy between 2010 and 2018 at our institution were included (n = 577). Pathology reports were reviewed for sites of lymph node metastases. Patients were excluded if nodal stations were not listed separately (n = 40). Age, sex, race, tumor location, TRG, pT stage, number of positive lymph nodes, number of positive nodal stations, and specific nodal stations were analyzed for risk of recurrence using univariable Cox regression, and significant covariates were included in multivariable Cox regression model. Results Of 537 patients, 193(36%) had pathologic nodal metastases. 153 patients(28%) had single-station disease: 135(88%) at the paraesophageal station, 16(10%) at the left gastric, 1 at the subcarinal and 1 at the paratracheal station(0.65% each). 32 patients(6.0%) had two-station and 8(1.5%) had three-station disease. The majority of patients with multiple positive nodal stations had positive nodes in the paraesophageal(90%) and/or left gastric artery stations(60%). On multivariable analysis, the number of positive nodal stations (HR 1.59, CI 1.35–1.84, p < 0.001), subcarinal (HR 2.78, CI 1.54–5.03, p < 0.001), and paraesophageal stations (HR 2.0, CI 1.58–2.54, p < 0.001) were associated with increased risk of recurrence. Conclusion Patients who have undergone neoadjuvant and R0 esophagectomy for adenocarcinoma often have lymph node metastases at time of surgery, most commonly at the paraesophageal station. The number of nodal stations, along with subcarinal and paraesophageal metastases, were associated with increased risk of recurrence.


2021 ◽  
Vol 67 (1) ◽  
pp. 88-94
Author(s):  
A.M. Krasnyi ◽  
S.V. Kurevlev ◽  
A.A. Sadekova ◽  
T.G. Sefikhanov ◽  
V.V. Kometova ◽  
...  

Aberrant methylation is strongly associated with development of cancer, but limited data exist on correlation between methylation and regional lymph node metastasis (RLNM). The aim of this research was to study using of methylation levels of WIF1, RASSF1A, CDO1 and MEST aberrant methylated genes in a primary breast cancer for prediction of regional lymph node metastases. We used MS-HRM (Methylation Sensitive High Resolution Melting) to assess methylation levels. The results were confirmed by pyrosequencing. The study included 66 women with LumA and 46 women with HER2- (LumB-), 22 and 26 of them had metastasis in at least one lymph node respectively. It was found that methylation levels between LumA and LumB subtypes differed significantly in genes: WIF1 (p<0.001), CDO1 (p=0.002) and MEST (p=0.033). In the Lum A subtype statistically significant differences in level of methylation of WIF1 gene between patients with metastases in RLNM and patients without metastases were found (p=0.03). Analysis of tumors longer than 2 cm in the LumA subtype, revealed an increase of statistical significance of WIF1 gene — p=0.009 (AUC (95%CI) = 0.76 (0.59−0.93)). In LumB- subtype RASSF1A, CDO1 and MEST had statistically significant differences in methylation level between groups (p=0.03, p=0.048 and p=0.045 respectively). ROC analysis showed that combining of three genes by logistic regression, AUC (95%CI) was 0.74 (0.6−0.88). Analysis of tumors longer than 2 cm, did not increase statistical significance for these genes (p=0.046; p=0.089 and p=0.076, respectively). Thus, the study of methylation in primary tumors may be useful for prediction of lymph node metastasis, as well as for better understanding of biological process inside breast cancer.


2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 106-106
Author(s):  
T. T. Higuchi ◽  
R. H. Breau ◽  
E. C. Umbreit ◽  
E. J. Bergstralh ◽  
L. J. Rangel ◽  
...  

106 Background: Some patients with lymph node metastases experience prolonged survival following radical prostatectomy. The purpose of this study was to determine the outcome of patients with clinically suspicious lymph nodes on preoperative imaging who underwent radical prostatectomy and lymphadenectomy. Methods: Patients with lymph node metastases diagnosed during radical prostatectomy from 1988-2003 were reviewed. Patients with preoperative CT or MRI images were included in the study. Radiology reports were reviewed to determine if patients had clinically suspicious lymphadenopathy (cN+). For all analyses, patients with cN+ were compared to those with clinically negative nodes (cN−). Results: Preoperative imaging was available in 202 men with lymph node metastasis at the time of prostatectomy. Of these 17% (34/202) were cN+. None had pre-operative lymph node biopsy and none had abandoned prostatectomy. At a median follow-up of 11.1 years, PSA recurrence occurred in 50% (17/34) and 49% (82/186), local recurrence in 18% (6/34) and 13% (22/186) and systemic progression in 32% (11/34) and 24% (40/186) of patients with cN+ and cN-, respectively. On multivariate analysis, cN+ was not associated with increased risk of death (HR 1.66, p=0.1). Conclusions: cN+ patients undergoing surgical therapy for prostate cancer may experience similar outcomes to cN− patients. The presence of clinically suspicious lymph nodes on preoperative imaging should not be an absolute contraindication for surgical therapy. No significant financial relationships to disclose.


Author(s):  
Wan Mohd Nazlee Wan Zainon ◽  
Wan Faiziah Wan Abdul Rahman ◽  
Maya Mazuwin Yahya ◽  
Nor Azwani Mat Nawi ◽  
Nurul Shamimi Suhaimi ◽  
...  

Abstract Background In cases of papillary thyroid carcinoma (PTC), lymph nodes are a typical site of metastasis. Extrathyroidal tissue involvement in differentiated thyroid carcinoma causes the disease to progress and affects the patients’ treatment options. Papillary thyroid carcinoma (PTC) is the common type in differentiated thyroid carcinoma (DTC), the other type is follicular thyroid carcinoma (FTC). Ectopic sites, such as intrathyroidal lymph node invasion in classical papillary thyroid malignancy, are extremely uncommon. It can be difficult to detect an intrathyroidal lymph node (ITLN) during a histopathological test, but it is important to do so since it affects the stage of the disease and subsequent treatment. Case presentation We present the case of a 63-year-old woman who presented with multinodular goitre and underwent total thyroidectomy. She was diagnosed with aberrant intrathyroidal lymph node metastases during pathological testing, resulting in an upgrade in treatment. Owing to the exceptionally unusual ectopic position of lymph node metastasis, in this case, there is a risk of diagnostic and therapeutic misinterpretation. This patient was treated with high-dose radioactive iodine in view of lymph node metastases. Conclusions Identification of ITLN by imaging characteristics is sometimes difficult, being often an intraoperative discovery and histopathological correlation that lead to upstage the disease and alter the final management.


2017 ◽  
Vol 2017 ◽  
pp. 1-3
Author(s):  
Joji Kawabe ◽  
Shigeaki Higashiyama ◽  
Mitsuharu Sougawa ◽  
Atsushi Yoshida ◽  
Kohei Kotani ◽  
...  

A woman in her 60s presented with a recurrent lymph node metastasis from a papillary thyroid carcinoma in the right parapharyngeal space. She had already undergone total thyroidectomy, five resections for cervical lymph node metastases, and right carotid rebuilding. Surgical resection of the current metastasis was impossible. 131I-radioiodine therapy (RIT) with 3.7 GBq 131I was not effective; therefore, stereotactic radiation therapy (SRT) using a CyberKnife radiotherapy system was scheduled. The prescription dose was 21 Gy, and a dose covering 95% of the planning target volume (PTV) in three fractions was administered. The PTV was 4,790 mm3. Follow-up magnetic resonance imaging conducted 3 and 12 months after the SRT demonstrated a remarkable and gradual reduction of the recurrent lymph node metastasis in the right parapharyngeal space and no evidence of recurrence. For multidisciplinary therapy of unresectable and/or RIT unresponsive locoregional lymph node metastases and recurrences of DTC, SRT using the CyberKnife system should be considered.


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