Residual melanoma after an excisional biopsy is an independent prognostic factor for local recurrence and overall survival

Hočevar, Marko; Dragonja, Z.; Pilko, Gasper; Gazić, Barbara; Žgajnar, Janez

doi:10.1016/j.ejso.2014.03.002

Cited by 13 publications

(7 citation statements)

References 14 publications

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“…After the complete resection of primary cutaneous melanoma, patients occasionally develop local recurrence, which is considered an independent prognostic factor [ 1 ]. This can be explained by hidden tumor-initiating cells containing tumor-derived genetic information as local minimal residual disease in the peritumoral area.…”

Section: Discussionmentioning

confidence: 99%

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Melanoma-Derived BRAFV600E Mutation in Peritumoral Stromal Cells: Implications for in Vivo Cell Fusion

Kurgyis

Kemény

Buknicz

et al. 2016

IJMS

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Melanoma often recurs in patients after the removal of the primary tumor, suggesting the presence of recurrent tumor-initiating cells that are undetectable using standard diagnostic methods. As cell fusion has been implicated to facilitate the alteration of a cell’s phenotype, we hypothesized that cells in the peritumoral stroma having a stromal phenotype that initiate recurrent tumors might originate from the fusion of tumor and stromal cells. Here, we show that in patients with BRAFV600E melanoma, melanoma antigen recognized by T-cells (MART1)-negative peritumoral stromal cells express BRAFV600E protein. To confirm the presence of the oncogene at the genetic level, peritumoral stromal cells were microdissected and screened for the presence of BRAFV600E with a mutation-specific polymerase chain reaction. Interestingly, cells carrying the BRAFV600E mutation were not only found among cells surrounding the primary tumor but were also present in the stroma of melanoma metastases as well as in a histologically tumor-free re-excision sample from a patient who subsequently developed a local recurrence. We did not detect any BRAFV600E mutation or protein in the peritumoral stroma of BRAFWT melanoma. Therefore, our results suggest that peritumoral stromal cells contain melanoma-derived oncogenic information, potentially as a result of cell fusion. These hybrid cells display the phenotype of stromal cells and are therefore undetectable using routine histological assessments. Our results highlight the importance of genetic analyses and the application of mutation-specific antibodies in the identification of potentially recurrent-tumor-initiating cells, which may help better predict patient survival and disease outcome.

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Section: Discussionmentioning

confidence: 99%

“…Melanoma is a highly aggressive malignancy, which often gives rise to metastases and local recurrences following tumor-free staging [ 1 , 2 ]. The histopathological examination of excisional and re-excisional samples and sentinel lymph node biopsies constitutes a fundamental part of the prognostic evaluation of this disease.…”

Section: Introductionmentioning

confidence: 99%

Melanoma-Derived BRAFV600E Mutation in Peritumoral Stromal Cells: Implications for in Vivo Cell Fusion

Kurgyis

Kemény

Buknicz

et al. 2016

IJMS

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“…Importantly, observations of accelerated metastatic tumor growth after excision of the primary tumor have been repeatedly reported for several cancers, including colorectal, ovarian, NSCLC, breast, pancreatic, and other cancers ( Table 1 ) [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Even the incisional biopsies, including the diagnostic core needle biopsy, might increase local tumor recurrence, lymph node metastases, and distant metastases [ 18 , 19 , 20 , 21 ]. However, our understanding of the cellular and molecular pathways of this phenomenon is still limited.…”

Section: Introductionmentioning

confidence: 99%

Neuroimmune Regulation of Surgery-Associated Metastases

Shurin

Baraldi

2021

Cells

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Surgery remains an essential therapeutic approach for most solid malignancies. Although for more than a century accumulating clinical and experimental data have indicated that surgical procedures themselves may promote the appearance and progression of recurrent and metastatic lesions, only in recent years has renewed interest been taken in the mechanism by which metastasizing of cancer occurs following operative procedures. It is well proven now that surgery constitutes a risk factor for the promotion of pre-existing, possibly dormant micrometastases and the acceleration of new metastases through several mechanisms, including the release of neuroendocrine and stress hormones and wound healing pathway-associated immunosuppression, neovascularization, and tissue remodeling. These postoperative consequences synergistically facilitate the establishment of new metastases and the development of pre-existing micrometastases. While only in recent years the role of the peripheral nervous system has been recognized as another contributor to cancer development and metastasis, little is known about the contribution of tumor-associated neuronal and neuroglial elements in the metastatic disease related to surgical trauma and wound healing. Specifically, although numerous clinical and experimental data suggest that biopsy- and surgery-induced wound healing can promote survival and metastatic spread of residual and dormant malignant cells, the involvement of the tumor-associated neuroglial cells in the formation of metastases following tissue injury has not been well understood. Understanding the clinical significance and underlying mechanisms of neuroimmune regulation of surgery-associated metastasis will not only advance the field of neuro–immuno–oncology and contribute to basic science and translational oncology research but will also produce a strong foundation for developing novel mechanism-based therapeutic approaches that may protect patients against the oncologically adverse effects of primary tumor biopsy and excision.

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“…After the complete resection of primary cutaneous melanoma, patients occasionally develop local recurrence which is considered as an independent prognostic factor [1]. This can be explained by hidden tumor-initiating cells containing tumor-derived information as local minimal residual disease in the peritumoral area.…”

Section: Discussionmentioning

confidence: 99%

“…Cutaneous melanoma is a highly aggressive malignancy, which often gives rise to metastases and local recurrences following series of tumor-free staging [1,2]. The histopathological examination of excisional and re-excisional samples together with sentinel lymph node biopsies constitutes a fundamental part of the prognostic evaluation of this disease.…”

Section: Role Of Tumor Heterogeneity In Tumor Progressionmentioning

confidence: 99%

Tumor cells can adopt the phenotype of stromal cells by cell fusion

Kurgyis¹

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Residual melanoma after an excisional biopsy is an independent prognostic factor for local recurrence and overall survival

Cited by 13 publications

References 14 publications

Melanoma-Derived BRAFV600E Mutation in Peritumoral Stromal Cells: Implications for in Vivo Cell Fusion

Melanoma-Derived BRAFV600E Mutation in Peritumoral Stromal Cells: Implications for in Vivo Cell Fusion

Neuroimmune Regulation of Surgery-Associated Metastases

Tumor cells can adopt the phenotype of stromal cells by cell fusion

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