Hypothesis: A Role for Telomere Crisis in Spontaneous Regression of Melanoma

Bastian, Boris C.

doi:10.1001/archderm.139.5.667

Cited by 30 publications

(14 citation statements)

References 8 publications

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“…macrophages that have ingested leftover melanin pigment. While it has been proposed that immune cell mediated killing of melanoma cells is the main mechanism leading to melanoma regression, telomere crisis has been proposed as an alternative mechanism (46). …”

Section: Melanocytic Neoplasms Originating From Epithelial Melanocytesmentioning

confidence: 99%

The Molecular Pathology of Melanoma: An Integrated Taxonomy of Melanocytic Neoplasia

Bastian

2014

Annu. Rev. Pathol. Mech. Dis.

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416

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Melanomas are comprised of multiple biologically distinct categories, which differ in cell of origin, age of onset, clinical and histologic presentation, pattern of metastasis, ethnic distribution, causative role of UV radiation, predisposing germ line alterations, mutational processes, and patterns of somatic mutations. Neoplasms are initiated by gain of function mutations in one of several primary oncogenes, typically leading to benign melanocytic nevi with characteristic histologic features. The progression of nevi is restrained by multiple tumor suppressive mechanisms. Secondary genetic alterations override these barriers and promote intermediate or overtly malignant tumors along distinct progression trajectories. The current knowledge about pathogenesis, clinical, histological and genetic features of primary melanocytic neoplasms is reviewed and integrated into a taxonomic framework.

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Section: Melanocytic Neoplasms Originating From Epithelial Melanocytesmentioning

confidence: 99%

The Molecular Pathology of Melanoma: An Integrated Taxonomy of Melanocytic Neoplasia

Bastian

2014

Annu. Rev. Pathol. Mech. Dis.

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416

388

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“…42,43 Other factors that can induce melanoma regression include decreased microphthalmia transcription factor activity within melanocytes. 44 Another mechanism, proposed by Bastian,45 suggests that decreased telomerase activity can lead to abnormal telomere function, and thus induce replicative senescence in melanoma cells, resulting in the generation of apoptotic bodies and a T lymphocyte response.…”

Section: Spontaneous Regression In Melanomamentioning

confidence: 99%

Regression in primary cutaneous melanoma: etiopathogenesis and clinical significance

Aung

Nagarajan

Prieto

2017

Laboratory Investigation

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Though not required currently for staging, regression is a histopathologic parameter typically reported upon diagnosis of an invasive primary cutaneous melanoma. The studies examining the prognostic significance of regression in patient outcome have yielded controversial findings; likely because the definition and assessment of regression have not been consistent, in addition to subjectivity of pathologists' interpretation. Regression is histologically characterized by variable decrease in the number of melanoma cells accompanied by the presence of a host response consisting of dermal fibrosis, inflammatory infiltrate, melanophages, ectatic blood vessels, epidermal attenuation, and/or apoptosis of keratinocytes or melanocytes; the relative extent of these features depends on the stage of the regression. However, the magnitudes to which these individual changes must be present to meet the threshold of histologic regression have not been well defined or agreed upon, and thus, the definition and classification of histologic regression in melanoma varies considerably among institutions and even among individual pathologists. In order to determine the clinical significance of histologic analysis of regression, there is a compelling need for a universal scheme to objectively define and assess histologic regression in primary cutaneous melanoma, so that the biologic and prognostic significance of this process may be completely understood.

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“…Although the current understanding of regression is clearly that of an immune-mediated, cancer-autonomous process [21], neither its biological significance nor the underlying molecular or genomic aberrations are so far recognized. Possible explanations vary from an increased T-cell response [54], an inhibited angiogenesis [53], to a forced apoptosis of tumor cells [53, 55]. Consequently there are different therapeutical implications of regression.…”

Section: Clinicopathological Parameters In Malignant Melanomamentioning

confidence: 99%

“…Especially in thin melanomas <1 mm, regression as a left-over of a presumably thicker tumor therefore still leads to wider surgical margins and a lower threshold for SLN biopsy [58]. The most convincing, although unproven, hypotheses for a regression-driven tumor progression so far are the Hammon's effect, which postulates a natural selection of aggressive residual tumor clones as a result of regression [59, 60] and Bastian's telomere crisis, which argues that a massive senescence and cellular apoptosis equally favor the selection of genomic aberrations and therefore progression [55]. Future epidemiologic studies investigating the impact of regression of the primary tumor for the prognosis of melanoma are certainly required to further investigate those intriguing details.…”

Section: Clinicopathological Parameters In Malignant Melanomamentioning

confidence: 99%

Prognostic Parameters for the Primary Care of Melanoma Patients: What Is Really Risky in Melanoma?

Göppner

Leverkus

2011

Journal of Skin Cancer

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Due to intensified research in recent years, the understanding of the molecular mechanisms involved in the development of melanoma has dramatically improved. The discovery of specific, causal mutations such as BRAF or KIT oncogenes not only renders a targeted and thus more effective therapeutic approach possible, but also gives rise to a new genetic-based classification. Targeting just a few out of several potential mutations, BRAF-Inhibitors such as PLX 4032 achieved already tremendous results in the therapy of metastatic melanoma. Up to now, the correlation of clinical, histomorphologic, and genetic features is, however, not understood. Even more, is it not well known precisely what kind of molecular changes predispose the primary melanoma for metastasis. The identification of morphological surrogates and prognostic parameters in tumors with such genetic alteration seems therefore crucial when differentiating and classifying this heterogeneous tumor entity in more detail and thus facilitates the stratification of prognosis as well as therapy. This review summarizes the current understanding of carcinogenesis and gives a detailed overview of known morphologic and potentially future genetic prognostic parameters in malignant melanoma.

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Hypothesis: A Role for Telomere Crisis in Spontaneous Regression of Melanoma

Cited by 30 publications

References 8 publications

The Molecular Pathology of Melanoma: An Integrated Taxonomy of Melanocytic Neoplasia

The Molecular Pathology of Melanoma: An Integrated Taxonomy of Melanocytic Neoplasia

Regression in primary cutaneous melanoma: etiopathogenesis and clinical significance

Prognostic Parameters for the Primary Care of Melanoma Patients: What Is Really Risky in Melanoma?

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