Mitotic rate is associated with positive lymph nodes in patients with thin melanomas

Wheless, Lee; Isom, Chelsea A.; Hooks, Mary; Kauffmann, Rondi M.

doi:10.1016/j.jaad.2017.11.041

Cited by 25 publications

(16 citation statements)

References 34 publications

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“…Our study aimed to develop a nomogram to accurately select patients with thin melanoma who may benefit from SLNB and evaluate its potential impact on the frequency of SLNB. Our results confirmed many previously known risk factors, such as age, depth, MR, Clark level, ulceration, and LVI, to be independently associated with SLN status . The nomogram accurately predicted the risk of a +SLN in the study population and considerably reduced the indication for SLNB in patients with thin melanoma.…”

Section: Discussionsupporting

confidence: 86%

“…Accordingly, SLNB should be considered for patients with thin melanomas with a BT ≥0.8 mm or with ulceration, and for patients with thinner melanomas with other adverse features (mitotic rate [MR] ≥2/mm 2 , lymphovascular invasion [LVI], and/or younger age) . In addition to these adverse features, others such as Clark level, regression, and vertical growth phase have been shown to be associated with +SLN in patients with thin melanoma . However, it is unknown whether a combination of these risk factors could identify a group of patients at higher risk of a +SLN for which a SLNB could be justified, and consequently, accurate selection of patients in this population for SLNB remains a challenge …”

Section: Introductionmentioning

confidence: 99%

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A nomogram to predict node positivity in patients with thin melanomas helps inform shared patient decision making

Friedman¹,

Lyon²,

Torphy³

et al. 2019

Journal of Surgical Oncology

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Objective: To develop a nomogram to estimate the probability of positive sentinel lymph node (+SLN) for patients with thin melanoma and to characterize its potential impact on sentinel lymph node biopsy (SLNB) rates.Methods: Patients diagnosed with thin (0.5-1.0 mm) melanoma were identified from the National Cancer Database 2012 to 2015. A multivariable logistic regression model was used to examine factors associated with +SLN, and a nomogram to predict +SLN was constructed. Nomogram performance was evaluated and diagnostic test statistics were calculated.Results: Of the 21 971 patients included 10 108 (46.0%) underwent SLNB, with a 4.0% +SLN rate. On multivariable analysis, age, Breslow thickness, lymphovascular invasion, ulceration, and Clark level were significantly associated with SLN status. The area under the receiver operating curve was 0.67 (95% confidence interval, 0.65-0.70). While 15 249 (69.4%) patients had either T1b tumors or T1a tumors with at least one adverse feature, only 2846 (13.0%) had a nomogram predicted probability of a +SLN ≥5%. Using this cutoff, the indication for a SLNB in these patients would be reduced by 81.3% as compared to the American Joint Committee on Cancer 8th edition staging criteria. Conclusions:The risk predictions obtained from the nomogram allow for more accurate selection of patients who could benefit from SLNB.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

A nomogram to predict node positivity in patients with thin melanomas helps inform shared patient decision making

Friedman¹,

Lyon²,

Torphy³

et al. 2019

Journal of Surgical Oncology

View full text Add to dashboard Cite

show abstract

“…Pathological staging that primarily focuses on tumor thickness is still applied as an estimate of the clinical behavior of the primary melanoma [33]. The mitotic score at the primary site is also often assessed [34,35]. Nevertheless, as a consequence of the diverse and contradictory information surrounding patient survival when analyzing both primary and metastatic melanomas, the prognostic value of BRAF mutations is still under discussion [25,[36][37][38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

The Hidden Story of Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma—Association with Clinical Outcome and Tumor Phenotypes

Betancourt

Szász

Kuras

et al. 2019

Cancers

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In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter- and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma.

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“…Pathological staging that primarily focuses on tumor thickness is still applied as an estimate of the clinical behavior of the primary melanoma [36]. The mitotic score at the primary site is also often assessed [37,38]. Nevertheless, the prognostic value of As a consequence of the diverse and contradictory information surrounding patient survival when analyzing both primary and metastatic melanomas the prognostic value of BRAF mutations is still under discussion [25,29,[39][40][41][42][43].…”

Section: Discussionmentioning

confidence: 99%

The Hidden Story on Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma – Association with Clinical Outcome and Tumor Phenotypes

Betancourt¹,

Szász²,

Kuras³

et al. 2019

Preprint

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In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas do clearly reveal the existence of inter- and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression for the mutated protein is associated with a more aggressive tumor progression. Our study design that is comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis may enable the eventual delineation of patient responders/non-responders and the subsequent therapy of malignant melanoma.

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Mitotic rate is associated with positive lymph nodes in patients with thin melanomas

Abstract: Mitotic rate was strongly associated with the odds of having a positive lymph node and should continue to be reported on pathology reports.

Cited by 25 publications

References 34 publications

A nomogram to predict node positivity in patients with thin melanomas helps inform shared patient decision making

A nomogram to predict node positivity in patients with thin melanomas helps inform shared patient decision making

The Hidden Story of Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma—Association with Clinical Outcome and Tumor Phenotypes

The Hidden Story on Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma – Association with Clinical Outcome and Tumor Phenotypes

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Mitotic rate is associated with positive lymph nodes in patients with thin melanomas

Abstract: Mitotic rate was strongly associated with the odds of having a positive lymph node and should continue to be reported on pathology reports.

Cited by 25 publications

References 34 publications

A nomogram to predict node positivity in patients with thin melanomas helps inform shared patient decision making

A nomogram to predict node positivity in patients with thin melanomas helps inform shared patient decision making

The Hidden Story of Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma—Association with Clinical Outcome and Tumor Phenotypes

The Hidden Story on Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma &ndash; Association with Clinical Outcome and Tumor Phenotypes

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The Hidden Story on Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma – Association with Clinical Outcome and Tumor Phenotypes