Prognostic implications of lymph node involvement in bladder cancer: are we understaging using current methods?

Watts, Kara; Ristau, Benjamin T.; Yamase, Harold; Taylor, John A.

doi:10.1111/j.1464-410x.2011.10330.x

Cited by 14 publications

(3 citation statements)

References 63 publications

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“…Bladder cancer ranks fourth in men and eighth in women among the most common malignancies in terms of frequency (27). However, little progress was made in the past decades toward prolonged survival of high-grade bladder cancer, leaving it still a lethal disease (28).…”

Section: Discussionmentioning

confidence: 99%

A Pre-operative Nomogram for Prediction of Lymph Node Metastasis in Bladder Urothelial Carcinoma

Wang

Jiang

et al. 2019

Front. Oncol.

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The status of lymph node (LN) metastases plays a decisive role in the selection of surgical procedures and post-operative treatment. Several histopathologic features, known as predictors of LN metastasis, are commonly available post-operatively. Medical imaging improved pre-operative diagnosis, but the results are not fully satisfactory due to substantial false positives. Thus, a reliable and robust method for pre-operative assessment of LN status is urgently required. We developed a prediction model in a training set from the TCGA-BLCA cohort including 196 bladder urothelial carcinoma samples with confirmed LN metastasis status. Least absolute shrinkage and selection operator (LASSO) regression was harnessed for dimension reduction, feature selection, and LNM signature building. Multivariable logistic regression was used to develop the prognostic model, incorporating the LNM signature, and a genomic mutation of MLL2 , and was presented with a LNM nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was evaluated by the testing set from the TCGA cohort and independent validation was assessed by two independent cohorts. The LNM signature, which consisted of 48 selected features, was significantly associated with LN status ( p < 0.005 for both the training and testing sets of the TCGA cohort). Predictors contained in the individualized prediction nomogram included the LNM signature and MLL2 mutation status. The model demonstrated good discrimination, with an area under the curve (AUC) of 98.7% (85.3% for testing set) and good calibration with p = 0.973 (0.485 for testing set) in the Hosmer-Lemeshow goodness of fit test. Decision curve analysis demonstrated that the LNM nomogram was clinically useful. This study presents a pre-operative nomogram incorporating a LNM signature and a genomic mutation, which can be conveniently utilized to facilitate pre-operative individualized prediction of LN metastasis in patients with bladder urothelial carcinoma.

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Section: Discussionmentioning

confidence: 99%

A Pre-operative Nomogram for Prediction of Lymph Node Metastasis in Bladder Urothelial Carcinoma

Wang

Jiang

et al. 2019

Front. Oncol.

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“…Presently, there are no defined tumor markers available for stratifying patients with respect to disease progression, prognosis or treatment, and no predictors of metastatic potential. Most patients with advanced cancer ultimately succumb to their disease with the most significant prognostic factor being the presence of LN metastasis [4]. While much work has been done on identifying the presence of metastatic tumor cells in LNs [reviewed in Watts el al., [4]], little research currently explores the ability to predict the likelihood of harboring or developing metastasis based on primary tumor characteristics.…”

Section: Introductionmentioning

confidence: 99%

Increased expression of L-selectin (CD62L) in high-grade urothelial carcinoma: A potential marker for metastatic disease

Choudhary

Hegde

Voznesensky

et al. 2015

Urologic Oncology: Seminars and Original Investigations

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Introduction L-selectin (CD62L) is a vascular adhesion molecule constitutively expressed on leucocytes with a primary function of directing leucocyte migration and homing of lymphocytes to lymph nodes (LNs). In a gene expression microarray study comparing laser captured micro-dissected (LCM) high grade muscle invasive bladder cancer (MIBC) without prior treatment and low grade bladder cancer (LGBC) human samples, we found CD62L to be the highest differentially expressed gene. We sought to examine the differential expression of CD62L in MIBCs and its clinical relevance. Methods Unfixed fresh and formalin fixed paraffin-embedded human bladder cancer specimens and serum samples were obtained from the UCHC tumor bank. Tumor cells were isolated from frozen tumor tissue sections by LCM followed by RNA isolation. qPCR was used to validate the level of CD62L transcripts. Immunohistochemistry and ELISA were performed to evaluate the CD62L protein localization and expression level. Flow cytometry was used to identify the relative number of cells expressing CD62L in fresh tumor tissue. In silico studies were performed using the Oncomine Database. Results Immunostaining showed a uniformly higher expression of CD62L in MIBC specimens vs. LGBCs specimens. Further, CD62L localization was seen in foci of metastatic tumor cells in LN specimens from patients with high grade MIBC and known nodal involvement. Upregulated expression of CD62L was also observed by flow cytometric analysis of freshly isolated tumor cells from biopsies of high grade cancers vs. LGBC specimens. Circulating CD62L levels were also found to be higher in serum samples from patients with high grade metastatic vs. high grade non-metastatic MIBC. In addition, in silico analysis of Oncomine Microarray Database showed a significant correlation between CD62L expression and tumor aggressiveness and clinical outcomes. Conclusion These data confirm the expression of CD62L on urothelial carcinoma cells and suggest that CD62L may serve as biomarker to predict the presence of or risk for developing metastatic disease in patients with bladder cancer.

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“…The bladder carcinoma (BCa) is the fifth most common cancer, which accounts for 85‐90% of the primary carcinomas with increasing incidence worldwide [1, 2]. Although the research on BCa was advanced rapidly in the last decade, the pathogenesis of BCa remains unknown; the prognosis of patients with BCa is unsatisfactory [3].…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase B Promotes Radiation‐Induced Regulatory T Cell Survival in Bladder Carcinoma

2012

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Radiotherapy is an efficient remedy in the treatment for bladder carcinoma (BCa); still, some cancer cells can survive from the radiation; the therapeutic effect is to be improved. Regulatory T cell (Treg)‐induced tumour tolerance and Akt expression play important roles in the tumour survival. This study aims to elucidate the role of radiation induces Akt expression in regulatory T cells (Tregs). The surgically removed BCa tissue was collected from 26 patients treated with or without radiotherapy. The frequency of Tregs and apoptotic Tregs in BCa tissue was assessed by flow cytometry. A cell culture model was employed to investigate the mechanism by which the tumour‐infiltrating Tregs survive from radiation. After radiotherapy, the frequency of Treg was increased in the BCa tissue; the apoptotic Tregs were decreased; the expression of Akt was increased in remained Tregs. The results were reproduced in vitro with a cell culture model. The addition of Akt inhibitor blocked the radiation‐induced Treg survival in culture. Akt plays an important role in the radiation‐induced tumour‐infiltrating Treg survival in BCa.

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Prognostic implications of lymph node involvement in bladder cancer: are we understaging using current methods?

Cited by 14 publications

References 63 publications

A Pre-operative Nomogram for Prediction of Lymph Node Metastasis in Bladder Urothelial Carcinoma

A Pre-operative Nomogram for Prediction of Lymph Node Metastasis in Bladder Urothelial Carcinoma

Increased expression of L-selectin (CD62L) in high-grade urothelial carcinoma: A potential marker for metastatic disease

Protein Kinase B Promotes Radiation‐Induced Regulatory T Cell Survival in Bladder Carcinoma

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