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Issues affecting molecular staging in the management of patients with melanoma.

Palmieri G, Casula M, Sini MC, Ascierto PA, Cossu A - J. Cell. Mol. Med. (2007 Sep-Oct)

Bottom Line: Detection of occult melanoma cells in peripheral blood (circulating metastatic cells [CMC]) or in sentinel lymph nodes (sentinel node metastatic cells [SNMC]), could significantly contribute to better predict survival in melanoma patients.Increasing evidence suggest that melanoma develops as a result of accumulated abnormalities in genetic pathways within the melanocytic lineage.The different molecular mechanisms may have separate roles or cooperate during all evolutionary phases of melanocytic tumourigenesis, generating different subsets of melanoma patients with distinct aggressiveness, clinical behaviour, and response to therapy.

View Article: PubMed Central - PubMed

Affiliation: Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Li Punti-Sassari, Italy. gpalmieri@yahoo.com

ABSTRACT
Prediction of metastatic potential remains one of the main goals to be pursued in order to better assess the risk subgroups of patients with melanoma. Detection of occult melanoma cells in peripheral blood (circulating metastatic cells [CMC]) or in sentinel lymph nodes (sentinel node metastatic cells [SNMC]), could significantly contribute to better predict survival in melanoma patients. An overview of the numerous published studies indicate the existence of several drawbacks about either the reliability of the approaches for identification of occult melanoma cells or the clinical value of CMC and SNMC as prognostic factors among melanoma patients. In this sense, characterization of the molecular mechanisms involved in development and progression of melanoma (referred to as melanomagenesis) could contribute to better classify the different subsets of melanoma patients. Increasing evidence suggest that melanoma develops as a result of accumulated abnormalities in genetic pathways within the melanocytic lineage. The different molecular mechanisms may have separate roles or cooperate during all evolutionary phases of melanocytic tumourigenesis, generating different subsets of melanoma patients with distinct aggressiveness, clinical behaviour, and response to therapy. All these features associated with either the dissemination of occult metastatic cells or the melanomagenesis might be useful to adequately manage the melanoma patients with different prognosis as well as to better address the different melanoma subsets toward more appropriate therapeutic approaches.

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Related in: MedlinePlus

Comparison between circulating metastatic cells (CMC) detection and prognosis. The different hypotheses to explain the controversial data about prognostic value of RT-PCR assays on peripheral blood of melanoma patients at the time of diagnosis (baseline) are provided. On the left, representation of the cancer cells entering (top), surviving (middle) and exiting (bottom) the blood stream.
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fig01: Comparison between circulating metastatic cells (CMC) detection and prognosis. The different hypotheses to explain the controversial data about prognostic value of RT-PCR assays on peripheral blood of melanoma patients at the time of diagnosis (baseline) are provided. On the left, representation of the cancer cells entering (top), surviving (middle) and exiting (bottom) the blood stream.

Mentions: In this light, a prolonged presence of melanoma cells in blood stream may indeed contribute to select viable cancer cells with better capacity to begin colonization process at the distant site. All the above-mentioned studies were based on RT-PCR analyses of baseline blood samples obtained from melanoma patients at time of diagnosis (generally, early-stage patients have been enrolled if no more than 4 weeks had elapsed from the surgical treatment, whereas those with advanced disease had baseline blood sample collected before systemic therapy). One could speculate that, after an initial peak of circulating cancer cells (strictly correlated with the tumour burden) at the time of surgical excision of the primary melanoma, progressive disappearance of CMC from peripheral blood (i.e. due to lack of their viability in circulation) could be related to the favourable outcome in patients classified as PCR-positive at baseline. Conversely, appearance of CMC in peripheral blood during follow-up (i.e. due to the existence of previously quiescent melanoma cells, which might have acquired the capability of entering the blood stream) could justify the observation of relapses in PCR-negative patients at baseline (Fig. 1).


Issues affecting molecular staging in the management of patients with melanoma.

Palmieri G, Casula M, Sini MC, Ascierto PA, Cossu A - J. Cell. Mol. Med. (2007 Sep-Oct)

Comparison between circulating metastatic cells (CMC) detection and prognosis. The different hypotheses to explain the controversial data about prognostic value of RT-PCR assays on peripheral blood of melanoma patients at the time of diagnosis (baseline) are provided. On the left, representation of the cancer cells entering (top), surviving (middle) and exiting (bottom) the blood stream.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401272&req=5

fig01: Comparison between circulating metastatic cells (CMC) detection and prognosis. The different hypotheses to explain the controversial data about prognostic value of RT-PCR assays on peripheral blood of melanoma patients at the time of diagnosis (baseline) are provided. On the left, representation of the cancer cells entering (top), surviving (middle) and exiting (bottom) the blood stream.
Mentions: In this light, a prolonged presence of melanoma cells in blood stream may indeed contribute to select viable cancer cells with better capacity to begin colonization process at the distant site. All the above-mentioned studies were based on RT-PCR analyses of baseline blood samples obtained from melanoma patients at time of diagnosis (generally, early-stage patients have been enrolled if no more than 4 weeks had elapsed from the surgical treatment, whereas those with advanced disease had baseline blood sample collected before systemic therapy). One could speculate that, after an initial peak of circulating cancer cells (strictly correlated with the tumour burden) at the time of surgical excision of the primary melanoma, progressive disappearance of CMC from peripheral blood (i.e. due to lack of their viability in circulation) could be related to the favourable outcome in patients classified as PCR-positive at baseline. Conversely, appearance of CMC in peripheral blood during follow-up (i.e. due to the existence of previously quiescent melanoma cells, which might have acquired the capability of entering the blood stream) could justify the observation of relapses in PCR-negative patients at baseline (Fig. 1).

Bottom Line: Detection of occult melanoma cells in peripheral blood (circulating metastatic cells [CMC]) or in sentinel lymph nodes (sentinel node metastatic cells [SNMC]), could significantly contribute to better predict survival in melanoma patients.Increasing evidence suggest that melanoma develops as a result of accumulated abnormalities in genetic pathways within the melanocytic lineage.The different molecular mechanisms may have separate roles or cooperate during all evolutionary phases of melanocytic tumourigenesis, generating different subsets of melanoma patients with distinct aggressiveness, clinical behaviour, and response to therapy.

View Article: PubMed Central - PubMed

Affiliation: Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Li Punti-Sassari, Italy. gpalmieri@yahoo.com

ABSTRACT
Prediction of metastatic potential remains one of the main goals to be pursued in order to better assess the risk subgroups of patients with melanoma. Detection of occult melanoma cells in peripheral blood (circulating metastatic cells [CMC]) or in sentinel lymph nodes (sentinel node metastatic cells [SNMC]), could significantly contribute to better predict survival in melanoma patients. An overview of the numerous published studies indicate the existence of several drawbacks about either the reliability of the approaches for identification of occult melanoma cells or the clinical value of CMC and SNMC as prognostic factors among melanoma patients. In this sense, characterization of the molecular mechanisms involved in development and progression of melanoma (referred to as melanomagenesis) could contribute to better classify the different subsets of melanoma patients. Increasing evidence suggest that melanoma develops as a result of accumulated abnormalities in genetic pathways within the melanocytic lineage. The different molecular mechanisms may have separate roles or cooperate during all evolutionary phases of melanocytic tumourigenesis, generating different subsets of melanoma patients with distinct aggressiveness, clinical behaviour, and response to therapy. All these features associated with either the dissemination of occult metastatic cells or the melanomagenesis might be useful to adequately manage the melanoma patients with different prognosis as well as to better address the different melanoma subsets toward more appropriate therapeutic approaches.

Show MeSH
Related in: MedlinePlus