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Multimarker reverse transcriptase-polymerase chain reaction assay in lymphatic drainage and sentinel node tumor
Piotr Rutkowski1, Zbigniew I Nowecki, Alexander C J van Akkooi
1Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. rutkowskip@coi.waw.pl
Annals of Surgical Oncology
|July 8, 2010
Summary
Sentinel lymph node tumor burden and molecular markers in lymph fluid significantly predict melanoma survival. Positive results correlate with shorter disease-free and overall survival in patients with melanoma.
Area of Science:
- Oncology
- Dermatology
- Surgical Pathology
Background:
- Accurate prognostic assessment is crucial for melanoma patients with positive sentinel lymph node (SN) biopsy.
- Traditional pathological features of SN metastases require further refinement for precise survival prediction.
- Molecular detection of melanoma cells in lymph fluid offers a potential complementary prognostic tool.
Purpose of the Study:
- To evaluate the prognostic value of sentinel lymph node (SN) tumor burden and molecular markers in lymph fluid (LY) for melanoma patients.
- To correlate pathological and molecular findings with overall survival (OS) and disease-free survival (DFS).
- To identify independent prognostic factors in patients with positive SN biopsy.
Main Methods:
- Analysis of 368 SN-positive melanoma patients post-completion lymph node dissection (CLND).
- Assessment of SN microanatomic location and tumor burden using Rotterdam criteria.
- Multimarker reverse transcriptase-polymerase chain reaction (MM-RT-PCR) analysis of 24-hour collected lymph fluid (LY) for melanoma cell markers (tyrosinase, MART1, uMAGE).
Main Results:
- Univariate analysis identified higher Breslow thickness, ulceration, Clark level, male gender, multiple metastatic nodes, extracapsular extension, non-SN metastases, micrometastasis size ≥ 0.1 mm, and positive LY MM-RT-PCR as negative prognostic factors for OS.
- SN tumor burden demonstrated a linear correlation with Breslow thickness; 5-year OS rates decreased significantly with increasing tumor burden (<0.1 mm: 84%; 1-1.0 mm: 66%; >1.0 mm: 44%).
- Multivariate analysis revealed male gender, primary tumor ulceration, ≥ 4 involved nodes, and micrometastasis size >1.0 mm as independent predictors of shorter OS. Positive LY MM-RT-PCR (HR 3.2) was also an independent predictor.
Conclusions:
- Sentinel lymph node tumor burden categories and positive lymph fluid MM-RT-PCR results provide significant, independent prognostic information in SN-positive melanoma patients.
- These factors are strongly correlated with reduced disease-free survival and overall survival.
- Incorporating these molecular and refined pathological assessments can improve prognostic accuracy for melanoma management.