Quantification of tumor cell burden by analysis of single cell lymph node disaggregates in metastatic prostate cancer

Schilling, David; Hennenlotter, Joerg; Sotlar, Karl; Kuehs, Ursula; Senger, Erika; Nagele, Udo; Boekeler, Ulf; Ulmer, Anja; Stenzl, Arnulf

doi:10.1002/pros.21145

Cited by 12 publications

(3 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In summary, we provide evidence that quantification of lymphatic cancer cell dissemination is feasible and can be combined with other quantitative and qualitative characteristics of the primary tumor for accurate individual outcome prediction, probably not only for melanoma but also for other types of solid cancer [34] . It will be important to validate the findings in an independent study before the assay and the prediction model are used clinically.…”

Section: Discussionmentioning

confidence: 82%

Quantitative Measurement of Melanoma Spread in Sentinel Lymph Nodes and Survival

et al. 2014

Self Cite

View full text Add to dashboard Cite

In this study, Klein and colleagues investigated the impact of minimal cancer sentinel lymph node spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival. The authors found that cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death and the best predictor of outcome was a model based on combined quantitative effects of DCCD, tumor thickness, and ulceration. Please see later in the article for the Editors' Summary

show abstract

Section: Discussionmentioning

confidence: 82%

Quantitative Measurement of Melanoma Spread in Sentinel Lymph Nodes and Survival

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although further experiments are required, it is interesting to speculate that the LN metastases arise from basal cell populations that are transitioning to more luminal phenotypes. Interestingly, over 50% of human prostate cancer cases with minimal primary site disease show evidence of PSA-positivity in the bone marrow (2) or disseminated tumor cells in local lymph nodes (30), strongly suggesting early metastatic dissemination. Given that the majority of initial CaP metastases in the clinical setting are found in local draining LN and bones…”

Section: Discussionmentioning

confidence: 99%

A Transgenic Mouse Model for Early Prostate Metastasis to Lymph Nodes

Akakura

Peresie

et al. 2014

Cancer Research

View full text Add to dashboard Cite

The emergence of recurrent, metastatic prostate cancer following the failure of androgen-deprivation therapy represents the lethal phenotype of this disease. However, little is known regarding the genes and pathways that regulate this metastatic process, and moreover, it is unclear whether metastasis is an early or late event. The individual genetic loss of the metastasis suppressor, SSeCKS/Gravin/AKAP12, or Rb, genes that are downregulated or deleted in human prostate cancer, results in prostatic hyperplasia. Here, we show that the combined loss of Akap12 and Rb results in prostatic intraepithelial neoplasia (PIN) that fails to progress to malignancy after 18 months. Strikingly, 83% of mice with PIN lesions exhibited metastases to draining lymph nodes, marked by relatively differentiated tumor cells expressing markers of basal (p63, cytokeratin 14) and luminal (cytokeratin 8 and androgen receptor) epithelial cells, although none expressed the basal marker, cytokeratin 5. The finding that PIN lesions contain increased numbers of p63/AR-positive, cytokeratin 5-negative basal cells compared to WT or Akap12−/− prostate lobes suggests that these transitional cells may be the source of the LN metastases. Taken together, these data suggest that in the context of Rb loss, Akap12 suppresses the oncogenic proliferation and early metastatic spread of basal-luminal prostate tumor cells.

show abstract

“…The detection of micrometastases and disseminated tumour cells may necessitate the processing of LN specimens with a resolution beyond 200 µm. Recently, we proposed a novel method to monitor even single disseminated tumour cells in a LN [28]. By calculating the tumour cell density, we proposed a novel parameter to measure the true tumour cell burden.…”

Section: Discussionmentioning

confidence: 99%

Prospective assessment of histological serial sectioning of pelvic lymph nodes in prostate cancer: a cost‐benefit analysis

et al. 2012

Self Cite

View full text Add to dashboard Cite

What ' s known on the subject? and What does the study add? Metastatic spread to the regional lymph nodes (LNs) is the single worst predictor of survival in prostate cancer. Knowledge of the LN status is crucial, as the treatment strategy is substantially altered in non-organ-confi ned disease. Current routine pathological protocols for evaluation of LN resection specimens do not demand a minimum of cross-sections per LN to be examined. Depending on the LN size, usually one to two sections are examined. This might lead to underestimation of the true metastatic burden.The present study shows that additional examination of cross-sections in pelvic LNs and applying prostate cancer-specifi c cytokeratine immunostaining does not lead to signifi cantly increased detection of prostate cancer metastases. However, the workload and the expenses were signifi cantly higher compared with routine evaluation. OBJECTIVE• To evaluate the diagnostic gain in the detection of lymph node (LN) metastases of prostate cancer and the additional expenses of histological step-section analysis, including immunohistochemistry compared with routine histopathological evaluation. PATIENTS AND METHODS• In a prospective study, 19 patients with prostate cancer at high risk of LN metastases ( > cT2c and/or PSA level of > 20 ng/mL and/or Gleason score > 8) underwent sentinel-guided LN resection.• All palpable LNs were submitted to step-section analysis in 200-μ m sections and concomitant immunohistochemical staining for cytokeratine (AE1/AE3), in addition to routine histopathology of one or two haematoxylin and eosin-stained sections per LN.• The number of positive LNs and LN-positive patients for each method was compared; additional expenses in labour time and material for the extended evaluation were estimated. RESULTS• In all, 413 LNs were resected; 220 LNs were palpable and were included in the study.• In seven of the 19 patients routine histopathological evaluation revealed LN metastases in 24 of 220 LNs (10.9%).• Extended LN evaluation with step sectioning and cytokeratin immunohistochemistry did not reveal any additional patients with LN metastases.• In one patient already diagnosed with LN metastases on routine histology, four additional LN metastases were detected upon extended LN evaluation. Three LNs of two patients, one of them pN0, contained disseminated tumour cells.• Compared with conventional histological evaluation, serial-section analysis and immunohistochemistry increased expenses in materials and labour time 18.7-fold. CONCLUSIONS• Serial-section analysis seems to have only a minimal diagnostic gain; however, valid conclusions cannot be drawn, as not all LNs were submitted to extended evaluation.• Considering the additional expenses, extensive LN evaluation in prostate cancer cannot generally be recommended. KEYWORDSprostate cancer , staging , lymph node metastases , step section analysis , immunohistochemistry Study Type -Therapy (case series) Level of Evidence 4

show abstract

Quantification of tumor cell burden by analysis of single cell lymph node disaggregates in metastatic prostate cancer

Cited by 12 publications

References 27 publications

Quantitative Measurement of Melanoma Spread in Sentinel Lymph Nodes and Survival

Quantitative Measurement of Melanoma Spread in Sentinel Lymph Nodes and Survival

A Transgenic Mouse Model for Early Prostate Metastasis to Lymph Nodes

Prospective assessment of histological serial sectioning of pelvic lymph nodes in prostate cancer: a cost‐benefit analysis

Contact Info

Product

Resources

About