Lymph Node Micrometastases in Lung Cancer

Effenberger, Katharina E.; Sienel, Wulf; Pantel, Klaus

doi:10.1007/978-0-387-69219-7_12

Cited by 3 publications

(2 citation statements)

References 34 publications

(42 reference statements)

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“…This expectation was based both on our previous molecular analyses of sentinel LNs from colon cancer patients [25], [26] and on previous reports of tumor cell dissemination in NSCLC patients [4], [27]. However, we did not observe any significant association between pN stage and our molecular LN analysis in the present study.…”

Section: Discussionsupporting

confidence: 69%

“…Several projects have aimed at finding markers to identify micrometastases and residual cancer cells, either as tumor cells in blood, lymph nodes (LN) or bone-marrow, or as RNA or proteins derived from cancer cells in blood, LNs or bone marrow [4], [5]. Common technologies for detecting metastases include reverse transcription polymerase chain reaction (RT-PCR), immunocytochemistry and immunohistochemistry.…”

Section: Introductionmentioning

confidence: 99%

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Novel Molecular Tumor Cell Markers in Regional Lymph Nodes and Blood Samples from Patients Undergoing Surgery for Non-Small Cell Lung Cancer

et al. 2013

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IntroductionRecent evidence suggests that microscopic lymph node metastases and circulating tumor cells may have clinical importance in lung cancer. The purpose of this study was to identify new molecular markers for tumor cells in regional lymph nodes (LNs) and peripheral blood (PB) from patients with non-small cell lung cancer (NSCLC).MethodsCandidate markers were selected based on digital transcript profiling and previous literature. KRT19, CEACAM5, EPCAM, DSG3, SFTPA, SFTPC and SFTPB mRNA levels were initially validated by real-time reverse transcription PCR-based quantification in 16 NSCLC tumors and 22 LNs and 12 PB samples from individuals without known cancer. Five of the candidate markers were selected for secondary validation by quantification in parallel tumor biopsies, regional LNs and PB samples from 55 patients undergoing surgery for NSCLC. LN and PB marker status were compared to clinicopathological patient data.ResultsAll selected markers except DSG3 were present at high levels in the primary tumors and at very low or non-detectable levels in normal LNs and PB in the first round of validation, indicating a potential for detecting tumor cells in NSCLC patients. The expression profiles of KRT19, CEACAM5, DSG3, SFTPA and SFTPC mRNA were confirmed in the larger group during the secondary validation. Using the highest normal LN level of each marker as threshold, 39 (71%) of the 55 patients had elevated levels of at least one marker in regional LNs. Similarly, 26 (47%) patients had elevated levels of at least one marker in PB. A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004).ConclusionsSeveral promising molecular tumor cell markers in regional LNs and PB were identified, including the new SFTPA and SFTPC mRNAs. Clinical follow-up in a larger cohort is needed to elucidate their prognostic value.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Novel Molecular Tumor Cell Markers in Regional Lymph Nodes and Blood Samples from Patients Undergoing Surgery for Non-Small Cell Lung Cancer

et al. 2013

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Vers une renaissance de la radiothérapie dans les cancers bronchiques non à petites cellules de stade précoce

Girard

Mornex

2008

Revue des Maladies Respiratoires

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A critical role for lymphatic endothelial heparan sulfate in lymph node metastasis

et al. 2010

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BackgroundLymph node metastasis constitutes a key event in tumor progression. The molecular control of this process is poorly understood. Heparan sulfate is a linear polysaccharide consisting of unique sulfate-modified disaccharide repeats that allow the glycan to bind a variety of proteins, including chemokines. While some chemokines may drive lymphatic trafficking of tumor cells, the functional and genetic importance of heparan sulfate as a possible mediator of chemokine actions in lymphatic metastasis has not been reported.ResultsWe applied a loss-of-function genetic approach employing lymphatic endothelial conditional mutations in heparan sulfate biosynthesis to study the effects on tumor-lymphatic trafficking and lymph node metastasis. Lymphatic endothelial deficiency in N-deacetylase/N-sulfotransferase-1 (Ndst1), a key enzyme involved in sulfating nascent heparan sulfate chains, resulted in altered lymph node metastasis in tumor-bearing gene targeted mice. This occurred in mice harboring either a pan-endothelial Ndst1 mutation or an inducible lymphatic-endothelial specific mutation in Ndst1. In addition to a marked reduction in tumor metastases to the regional lymph nodes in mutant mice, specific immuno-localization of CCL21, a heparin-binding chemokine known to regulate leukocyte and possibly tumor-cell traffic, showed a marked reduction in its ability to associate with tumor cells in mutant lymph nodes. In vitro modified chemotaxis studies targeting heparan sulfate biosynthesis in lymphatic endothelial cells revealed that heparan sulfate secreted by lymphatic endothelium is required for CCL21-dependent directional migration of murine as well as human lung carcinoma cells toward the targeted lymphatic endothelium. Lymphatic heparan sulfate was also required for binding of CCL21 to its receptor CCR7 on tumor cells as well as the activation of migration signaling pathways in tumor cells exposed to lymphatic conditioned medium. Finally, lymphatic cell-surface heparan sulfate facilitated receptor-dependent binding and concentration of CCL21 on the lymphatic endothelium, thereby serving as a mechanism to generate lymphatic chemokine gradients.ConclusionsThis work demonstrates the genetic importance of host lymphatic heparan sulfate in mediating chemokine dependent tumor-cell traffic in the lymphatic microenvironment. The impact on chemokine dependent lymphatic metastasis may guide novel therapeutic strategies.

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Lymph Node Micrometastases in Lung Cancer

Cited by 3 publications

References 34 publications

Novel Molecular Tumor Cell Markers in Regional Lymph Nodes and Blood Samples from Patients Undergoing Surgery for Non-Small Cell Lung Cancer

Novel Molecular Tumor Cell Markers in Regional Lymph Nodes and Blood Samples from Patients Undergoing Surgery for Non-Small Cell Lung Cancer

Vers une renaissance de la radiothérapie dans les cancers bronchiques non à petites cellules de stade précoce

A critical role for lymphatic endothelial heparan sulfate in lymph node metastasis

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