Quantitative Measurement of Melanoma Spread in Sentinel Lymph Nodes and Survival

Ulmer, Anja; Dietz, Klaus; Hodak, Isabelle; Polzer, Bernhard; Scheitler, Sebastian; Yıldız, Murat; Czyż, Zbigniew T.; Lehnert, Petra; Fehm, Tanja; Hafner, Christian; Schanz, Stefan; Röcken, Martin; Garbe, Claus; Breuninger, Helmut; Fierlbeck, Gerhard; Klein, Christoph A.

doi:10.1371/journal.pmed.1001604

Cited by 54 publications

(58 citation statements)

References 33 publications

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“…Riber-Hansen et al [16] proposed a more complex methodology -metastatic volume in sentinel nodeswhich they found to be an independent marker of disease progression (P < 0.0001). Another methodology was described by Ulmer et al [24], based on the number of disseminated cancer cells per million LN cells (disseminated cancer cell density), which is very similar to what we call MAR. This paper concludes that cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death [24].…”

Section: Discussionmentioning

confidence: 99%

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Metastatic area ratio can help predict nonsentinel node positivity in melanoma patients

Bertolli

Macedo²,

Pinto³

et al. 2016

Melanoma Research

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Several studies suggest that melanoma patients with a positive sentinel node biopsy (SNB) can avoid having complete nodal dissection on the basis of pathological features of the node. The aim of the study was to determine the value of metastatic area ratio as a predictive factor for nonsentinel node (NSN) positivity. A retrospective analysis was carried out of melanoma patients who underwent SNB in a single institution between 2000 and 2010. A total of 697 patients were evaluated. In 155 patients (22.2%), the SNB was positive; 146 lymphadenectomies were performed, and 23 patients in whom this was performed (15.8%) had positive NSN. In multivariate analyses, Breslow thickness of more than 2 mm, perinodal vascular invasion, and metastatic area ratio were significantly related to NSN positivity in the complete nodal dissection. Metastatic area ratio of a positive SNB can be valuable in predicting the risk of NSN positivity.

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Section: Discussionmentioning

confidence: 99%

“…Another methodology was described by Ulmer et al [24], based on the number of disseminated cancer cells per million LN cells (disseminated cancer cell density), which is very similar to what we call MAR. This paper concludes that cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death [24].…”

Section: Discussionmentioning

confidence: 99%

Metastatic area ratio can help predict nonsentinel node positivity in melanoma patients

Bertolli

Macedo²,

Pinto³

et al. 2016

Melanoma Research

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“…AJCC guidelines for sentinel lymph node biopsy have been recently updated to include patients who have been staged as T1b primary lesions (≤1.0 mm Breslow thickness with ulceration or mitoses ≥1 mm 2 ) [1], [2]. Thus, the increased use of sentinel lymph node biopsies in patients with melanoma have led to a higher frequency of nodal nevi discovered in regional lymph nodes [3], [4].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the differentiation between the nodal nevi and metastatic lymph nodes has a profound effect on the prognosis of the patient, as the recognition of the differences is important to avoid misdiagnosis and provide adequate therapy options [7], [8], [9]. Current gold standard for diagnosis of metastatic melanoma has been tissue morphology and histopathology; however, benign melanocytic nevus cells are often difficult to distinguish from metastatic melanoma [2], [3], [6], [9], [10].…”

Section: Introductionmentioning

confidence: 99%

Capsular nevus versus metastatic malignant melanoma – a diagnostic dilemma

Davis

Patil

Aydin

et al. 2016

International Journal of Surgery Case Reports

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HighlightsThere are many morphologic guidelines to recognize nodal nevus cells, but there are some cases where the prediction of behavior of certain cells may not be accurate solely based on histopathological findings.Advanced histopathological techniques including implementing multiple markers should be employed in scenarios where distinguishing metastatic melanocytes from capsular nevi prove to be difficult.We strongly encourage obtaining a second opinion from a second histopathologist, preferably at a high volume center in cases where benign and malignant distinctions are difficult to make.

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“…Thereby, cell‐to‐cell variations introduced by random‐priming (e.g., in multiple strand displacement methods) are excluded and variability is thus limited to minor differences of individual donor polymorphisms. The WGA method proved its reliability in hundreds of single cell experiments from clinical samples . Furthermore, using deterministic WGA allows investigating several amplified oncogenes from the same single cell in parallel and enables subsequent development of targeted multiplexing assays.…”

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confidence: 99%

Diagnostic pathology of early systemic cancer: ERBB2 gene amplification in single disseminated cancer cells determines patient survival in operable esophageal cancer

Hoffmann

Pasch

Schamberger

et al. 2017

Intl Journal of Cancer

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Early metastatic dissemination and evolution of disseminated cancer cells (DCCs) outside the primary tumor is one reason for the failure of adjuvant therapies because it generates molecular genotypes and phenotypes different from primary tumors, which still underlie therapy decisions. Since ERBB2 amplification in esophageal DCCs but not in primary tumor cells predict outcome, we aimed to establish an assay with diagnostic reliability for single DCCs or circulating tumor cells. For this, we evaluated copy number alterations of more than 600 single DCCs from multiple cancer types to define reference regions suitable for quantification of target regions, such as ERBB2. We then compared ERBB2 quantitative PCR (qPCR) measurements with fluorescent in situ hybridization (FISH) data of various breast cancer cell lines and identified the aberration-calling threshold. The method was applied to two independent cohorts of esophageal cancer patients from Hamburg (n = 59) and Düsseldorf (n = 53). We found a high correlation between the single cell qPCR assay and the standard FISH assay (R = 0.98) and significant associations between amplification and survival for both patient cohorts (Hamburg (HH), p = 0.033; Düsseldorf (D), p = 0.052; pooled HH + D, p = 0.002) when applied to DCCs of esophageal cancer patients. Detection of a single ERBB2-amplified DCC was the most important risk factor for death from esophageal cancer (relative risk = 4.22; 95% CI = 1.91-9.32; p < 0.001). In our study, we detected ERBB2-amplified cells in 7% of patients. These patients could benefit from anti-ERBB2 targeting therapies.

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Quantitative Measurement of Melanoma Spread in Sentinel Lymph Nodes and Survival

Cited by 54 publications

References 33 publications

Metastatic area ratio can help predict nonsentinel node positivity in melanoma patients

Metastatic area ratio can help predict nonsentinel node positivity in melanoma patients

Capsular nevus versus metastatic malignant melanoma – a diagnostic dilemma

Diagnostic pathology of early systemic cancer: ERBB2 gene amplification in single disseminated cancer cells determines patient survival in operable esophageal cancer

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