Marker Protein Expression Combined With Expression Heterogeneity is a Powerful Indicator of Malignancy in Acral Lentiginous Melanomas

Carapeto, Fernando; Comodo, Andréia Neves; Germano, Andressa; Guimarães, Daiane Pereira; Barcelos, Denise; Fernandes, Mariana; Landman, Gilles

doi:10.1097/dad.0000000000000635

Cited by 6 publications

(2 citation statements)

References 28 publications

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“…Cintra Lopes Carapeto et al [85] performed IHC to assess heterogeneity of marker expression in four different areas within each of 49 acral lentiginous melanoma tumors and 60 compound nevi. The most heterogeneous protein was MYC which was heterogeneous in 75% of tumors.…”

Section: Intratumor Heterogeneity In Melanomamentioning

confidence: 99%

“…Association between tumor heterogeneity and cancer progression as well as prognosis is poorly explored in melanoma. However, it was shown that heterogeneity of protein marker expression is a more powerful indicator of malignancy in acral lentiginous melanomas than protein marker expression alone [85] . Nonetheless, further studies are necessary.…”

Section: Implications For Diagnosis and Treatmentmentioning

confidence: 99%

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Intratumor and Intertumor Heterogeneity in Melanoma

Grzywa

Paskal

Włodarski

2017

Translational Oncology

245

216

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Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed.

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Section: Intratumor Heterogeneity In Melanomamentioning

confidence: 99%

Section: Implications For Diagnosis and Treatmentmentioning

confidence: 99%

Intratumor and Intertumor Heterogeneity in Melanoma

Grzywa

Paskal

Włodarski

2017

Translational Oncology

245

216

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BRAF Heterogeneity in Melanoma

Ito

Tanaka

Murata

et al. 2021

Curr. Treat. Options in Oncol.

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Acral Lentiginous Melanomas Harbour Intratumor Heterogeneity in BRAF Exon 15, With Mutations Distinct From V600E/V600K

Fernandes

Barcelos

Comodo

et al. 2019

The American Journal of Dermatopathology

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The choice of appropriate therapeutic strategies may be influenced by intratumor heterogeneity and makes cancer treatment considerably more challenging. We aimed to evaluate the heterogeneity of BRAF exon 15 mutations in different areas of acral lentiginous melanoma (ALM). The entire exon 15 was sequenced in 4 different areas of paraffin-embedded samples from 26 patients with ALM. A total of 26 of 49 cases of ≥1 mm in depth of ALM identified by clinical, anatomical, and pathological data fulfilled the inclusion and exclusion criteria for this study. Tumors had a mean Breslow depth of 7.2 mm and an average mitotic index of 3 mitosis/mm2. Mutations distinct from the common V600E and V600K were detected in 31%, and intratumor heterogeneity was observed in 31% of samples. Interestingly, 63.5% of all mutations had been previously associated with cancer. Most (62.5%) of the missense BRAF exon 15 mutations found in the ALM samples examined here were deemed “detrimental” for protein function according to at least 2 functional prediction programs, and 3 mutations (37.5%) were predicted to be “neutral,” with no effect on protein function. BRAF exon 15 mutations were detected frequently in ALM and displayed heterogeneity, a finding to be further investigated.

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Marker Protein Expression Combined With Expression Heterogeneity is a Powerful Indicator of Malignancy in Acral Lentiginous Melanomas

Abstract: We show that marker protein expression, when combined with heterogeneous expression as shown by immunohistochemistry, is a powerful indicator of malignancy in ALMs, especially, when protein pairs are combined.

Cited by 6 publications

References 28 publications

Intratumor and Intertumor Heterogeneity in Melanoma

Intratumor and Intertumor Heterogeneity in Melanoma

BRAF Heterogeneity in Melanoma

Acral Lentiginous Melanomas Harbour Intratumor Heterogeneity in BRAF Exon 15, With Mutations Distinct From V600E/V600K

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