Tumour thickness as a predictor of occult lymph node metastases in patients with stage I and II melanoma undergoing sentinel lymph node biopsy

Lens, Marko; Dawes, Martin; Newton-Bishop, Julia; Goodacre, Tim

doi:10.1046/j.1365-2168.2002.02236.x

Cited by 69 publications

(44 citation statements)

References 29 publications

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“…Similar findings have been reported before (38,39 Breslow's tumor thickness and MART-1 and tyrosinase mRNA levels has never before been addressed. We found a weak but significant correlation between primary tumor thickness and mRNA values for both genes.…”

Section: Discussionsupporting

confidence: 77%

Pathologic Assessment of Melanoma Sentinel Nodes: A Role for Molecular Analysis Using Quantitative Real-Time Reverse Transcription-PCR for MART-1 and Tyrosinase Messenger RNA

Abrahamsen

Sørensen²,

Nexø³

et al. 2005

Clinical Cancer Research

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Purpose: Molecular analysis of melanoma sentinel nodes (SN) is sensitive, but poorly specific because metastases cannot be distinguished from benign nevus inclusions (BNI). We investigated whether quantitative reverse transcription-PCR (RT-PCR) detection of MART-1 and tyrosinase mRNAs could improve this specificity and contribute to SN assessment.Experimental Design: Two hundred twenty SNs from 95 melanoma patients analyzed by extensive immunohistopathology and real-time quantitative RT-PCR.Results: Using histopathology, SNs and patients were allotted to three diagnostic groups: (a) metastasis positive, (b) BNI positive, and (c) melanocyte-free. Median MART-1 and tyrosinase mRNA levels in SNs were significantly different in patients with metastasis compared with patients with BNIs (P < 0.05) and patients without melanocytic lesions (P < 0.001). However, a ''gray-zone'' was observed where distinction, based on mRNA levels, could not be made between the three groups. For both genes, the highest mRNA level recorded in each RT-PCR-positive patient was positively correlated with Breslow's tumor thickness. For SNs with metastases, tumor burden was significantly correlated to the mRNA level. Using the presence of a MART-1 RT-PCR signal to detect patients with metastases, a sensitivity of 100% and a negative predictive value of 100% were achieved when extensive immunohistology was used as reference.Conclusions: Quantitative RT-PCR MART-1 and tyrosinase mRNA analysis cannot be used alone for SN diagnosis because of its poor specificity for melanoma metastasis. However, in approximately one third of cases without RT-PCR evidence of MART-1 expression, extensive histopathologic SN investigation is not necessary, thus substantially reducing the cost of SN analysis. The level of melanocyte-associated mRNA is associated with both tumor thickness and tumor burden as measured histopathologically, suggesting that this may be of prognostic value.

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Section: Discussionsupporting

confidence: 77%

Pathologic Assessment of Melanoma Sentinel Nodes: A Role for Molecular Analysis Using Quantitative Real-Time Reverse Transcription-PCR for MART-1 and Tyrosinase Messenger RNA

Abrahamsen

Sørensen²,

Nexø³

et al. 2005

Clinical Cancer Research

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“…In the case of malignant melanoma, positive nodes are only rarely found in patients with thin melanomas. 38 Therefore, sentinel node biopsy is not recommended for melanomas that are 0.75 mm or less in depth, and with no adverse features. Lymphatic invasion seems to occur more frequently in the later stages of melanoma.…”

Section: Discussionmentioning

confidence: 99%

Vascular invasion is an early event in pathogenesis of Merkel cell carcinoma

et al. 2010

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This study investigated vascular and especially lymphovascular invasion in primary Merkel cell carcinoma and its value as a prognostic factor. Paraffin-embedded blocks prepared from tumor samples obtained from126 patients diagnosed with Merkel cell carcinoma in 1979-2004 were immunohistochemically stained using antibodies CD31 and D2-40 to detect intravascular tumor emboli. This finding was compared with the clinical data and the disease outcome. Intravascular tumor cells were observed in 117 (93%) of the samples. The majority, 83 (66%), showed only lymphovascular invasion. Only blood vascular invasion was seen in four (3%) samples. In all, 30 (24%) samples demonstrated both lymphovascular invasion and blood vascular invasion. In only nine (7%) samples, there was no invasion within the vascular structures. The tumors lacking invasion were significantly smaller (Po0.01 and a ¼ 0.050) than those with vascular invasion, although lymphovascular invasion was observed even in the smallest tumor (0.3 cm) of this study. Already in the early stages of the disease, Merkel cell carcinoma seems to have the capacity to penetrate vessel walls. Our finding of the high frequency of lymphovascular invasion might therefore explain the extremely aggressive clinical behavior of Merkel cell carcinoma. This may support the role of sentinel node biopsy even in the case of very small primary Merkel cell carcinoma tumors.

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“…Indeed, 39 of 122 patients initially presumed to have only local (stage I) disease in fact had lymph node disease (stage II) detected by SLNB. This 32% frequency rate of pathologic lymph node involvement in patients with MCC is far higher than in patients with invasive melanoma (an approximately 5% incidence rate of positive SLNBs, 21 assuming an average tumor depth of about 0.8 mm 22 ). There were significant prognostic and therapeutic implications for this cohort: (1) the risk of relapse was 3 times higher in those with a positive SLNB relative to those with a negative SLNB, (2) the clinical decision regarding adjuvant nodal therapy was highly affected by SLNB status (36% of patients with a negative SLNB received adjuvant therapy to the node bed vs 91% of patients with a positive SLNB), and (3) in individuals with a positive SLNB, adjuvant nodal treatment was associated with a relapse-free survival rate of 51% at 3 years compared with 0% for those who did not receive adjuvant nodal therapy.…”

Section: Commentmentioning

confidence: 99%

Sentinel Lymph Node Biopsy for Evaluation and Treatment of Patients With Merkel Cell Carcinoma

Gupta¹,

Wang²,

Peñas³

et al. 2006

Arch Dermatol

353

231

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To determine the diagnostic accuracy and usefulness of sentinel lymph node biopsy (SLNB) and computed tomographic scans in the initial evaluation and treatment of patients with Merkel cell carcinoma (MCC).Design: Single-institution case series and literaturebased case-level meta-analysis.Setting: Academic cutaneous oncology clinic.Patients: Sixty-one adults with biopsy-proven MCC (30 who had undergone SLNB) plus 92 cases from the literature of patients who had undergone SLNB.Main Outcome Measures: Relapse-free survival. Results:In 122 patients with no nodal disease found by physical examination, SLNB findings revealed nodal involvement in 39 cases (32%). At 3 years, the recurrence rate for those with a positive SLNB was 3 times (60%) higher than for those with a negative SLNB (20%; P =.03). Patients with a positive SLNB who received adjuvant nodal therapy had a relapse-free survival rate of 51% at 3 years (n=26) compared with 0% for patients who did not re-

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Tumour thickness as a predictor of occult lymph node metastases in patients with stage I and II melanoma undergoing sentinel lymph node biopsy

Abstract: The Breslow thickness of primary melanoma predicts the presence of a sentinel node metastasis. The published data are not sufficient to demonstrate a correlation between other known prognostic indicators and a positive SLNB.

Cited by 69 publications

References 29 publications

Pathologic Assessment of Melanoma Sentinel Nodes: A Role for Molecular Analysis Using Quantitative Real-Time Reverse Transcription-PCR for MART-1 and Tyrosinase Messenger RNA

Pathologic Assessment of Melanoma Sentinel Nodes: A Role for Molecular Analysis Using Quantitative Real-Time Reverse Transcription-PCR for MART-1 and Tyrosinase Messenger RNA

Vascular invasion is an early event in pathogenesis of Merkel cell carcinoma

Sentinel Lymph Node Biopsy for Evaluation and Treatment of Patients With Merkel Cell Carcinoma

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