Impact of sentinel lymphadenectomy on survival in a murine model of melanoma

Abstract

Lymphatic mapping and sentinel lymph node biopsy-also termed sentinel lymphadenectomy (SL)-has become a standard of care for patients with primary invasive cutaneous melanoma. This technique has been shown to provide accurate information about the disease status of the regional lymph node basins at risk for metastasis, provide prognostic information, and provide durable regional lymph node control. The potential survival benefit afforded to patients undergoing SL is controversial. Central to this controversy is whether metastasis to regional lymph nodes occurs independent of or prior to widespread hematogenous dissemination. A related area of uncertainty is whether tumor cells residing within regional lymph nodes have increased metastatic potential. We have used a murine model of primary invasive cutaneous melanoma based on injection of B16-BL6 melanoma cells into the pinna to address two questions: (1) does SL plus wide excision of the primary tumor result in a survival advantage over wide excision alone; and (2) do melanoma cells growing within lymph nodes produce a higher incidence of hematogenous metastases than do cells growing at the primary tumor site? We found that SL significantly improved the survival of mice with small primary tumors. We found no difference in the incidence of lung metastases produced by B16-BL6 melanoma cells growing exclusively within regional lymph nodes and cells growing within the pinna.

Wnt5A Regulates Expression of Tumor-Associated Antigens in Melanoma via Changes in Signal Transducers and Activators of Transcription 3 Phosphorylation

“…Much discussion has focused on the origins of metastases in melanoma. Studies have shown that in animal models of melanoma, pulmonary metastases occur even in the absence of lymph node metastases, underscoring a potential difference between hematogenous and lymphatic routes of tumor cell dissemination (22). In support of this, recent studies have shown that even though younger patients develop more sentinel lymph node metastases than older patients, outcome is poorer for older patients, due to increased visceral metastases (23).…”

Lymphangiogenesis and lymphatic metastasis in breast cancer

“…Third, recent clinical trials showed significant benefit for patients with small melanoma tumors who underwent lymphadenectomy immediately, thus disputing the previous conclusion [114]. Fourth, experimental assessment of this question in a melanoma model also showed significant survival benefit of sentinel lymphadenectomy for mice bearing small tumors [115]. The same study also found that cells from primary tumors and sLN have equal metastatic potential to colonize distant organs [115], thus arguing against the hypothesis that nodal metastatic cells are biologically restricted to their first destination site.…”

“…Fourth, experimental assessment of this question in a melanoma model also showed significant survival benefit of sentinel lymphadenectomy for mice bearing small tumors [115]. The same study also found that cells from primary tumors and sLN have equal metastatic potential to colonize distant organs [115], thus arguing against the hypothesis that nodal metastatic cells are biologically restricted to their first destination site. Lastly, much of the recent information on tumor lymphatic biology directly contradicts the opinion that metastatic cells in the lymph nodes “venture no farther” [116].…”

Difference of interferon-α and interferon-β on melanoma growth and lymph node metastasis in mice

“…A murine model of sentinel lymph node metastasis on the basis of injection of human melanoma cells into the preauricular area of athymic nude mice was created as described previously [14]. The present study was performed under protocols approved by the Animal Care and Use Committee of the College of Medicine of Yonsei University.…”