Diagnostic utility of dual 5‐hydroxymethylcytosine/Melan‐A immunohistochemistry in differentiating nodal nevus from metastatic melanoma: An effective first‐line test for the workup of sentinel lymph node specimen

Siref, Andrew; Huynh, Carissa A.; Balzer, Bonnie; Frishberg, David P.; Essner, Richard; Shon, Wonwoo

doi:10.1111/cup.13412

Cited by 9 publications

(5 citation statements)

References 21 publications

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“…Also, conjunctival melanomas (n = 37) displayed a significant reduction or absence of 5-hmC compared to normal conjunctival nevi (n = 40) (5-hmC expression: 54% vs. 100%, respectively) [24]. To achieve higher diagnostic precision, Siref et al performed a dual 5-hmC/Melan-A immunohistochemical staining in 41 metastatic melanomas and 20 nodal nevi and found a total or partial loss of nuclear expression of 5-hmC in 97.56% of melanomas, while 100% of nodal nevi showed a strong expression [25]. Altogether, 5-hmC is increasingly lost in dysplastic melanocytic nevi and frequently absent in melanomas, which we confirm in our current findings.…”

Section: Discussionmentioning

confidence: 99%

Standardized Computer-Assisted Analysis of 5-hmC Immunoreactivity in Dysplastic Nevi and Superficial Spreading Melanomas

Koch,

Berking,

Erber

et al. 2023

IJMS

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5-Hydroxymethylcytosine (5-hmC) is an important intermediate of DNA demethylation. Hypomethylation of DNA is frequent in cancer, resulting in deregulation of 5-hmC levels in melanoma. However, the interpretation of the intensity and distribution of 5-hmC immunoreactivity is not very standardized, which makes its interpretation difficult. In this study, 5-hmC-stained histological slides of superficial spreading melanomas (SSM) and dysplastic compound nevi (DN) were digitized and analyzed using the digital pathology and image platform QuPath. Receiver operating characteristic/area under the curve (ROCAUC) and t-tests were performed. A p-value of <0.05 was used for statistical significance, and a ROCAUC score of >0.8 was considered a “good” result. In total, 92 5-hmC-stained specimens were analyzed, including 42 SSM (45.7%) and 50 DN (54.3%). The mean of 5-hmC-positive cells/mm2 for the epidermis and dermo-epidermal junction and the entire lesion differed significantly between DN and SSM (p = 0.002 and p = 0.006, respectively) and showed a trend towards higher immunoreactivity in the dermal component (p = 0.069). The ROCAUC of 5-hmC-positive cells of the epidermis and dermo-epidermal junction was 0.79, for the dermis 0.74, and for the entire lesion 0.76. These results show that the assessment of the epidermal with junctional expression of 5-hmC is slightly superior to dermal immunoreactivity in distinguishing between DN and SSM.

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Section: Discussionmentioning

confidence: 99%

Standardized Computer-Assisted Analysis of 5-hmC Immunoreactivity in Dysplastic Nevi and Superficial Spreading Melanomas

Koch,

Berking,

Erber

et al. 2023

IJMS

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“…A previous study reported the function of the biomarkers found in our study. The expression of Melan-AC is highly specific in differentiating lymph nodes from metastatic melanoma ( 22 ), whereas the prognostic function of Melan-AC remains unknown. Syn is abnormally regulated in many cancers and plays an important role in the proliferation and progression of tumor cells ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of an Immunohistochemical Signature in Patients With Head and Neck Mucosal Melanoma

Huang

et al. 2021

Front. Immunol.

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PurposeWe aimed to develop a prognostic immunohistochemistry (IHC) signature for patients with head and neck mucosal melanoma (MMHN).MethodsIn total, 190 patients with nonmetastatic MMHN with complete clinical and pathological data before treatment were included in our retrospective study.ResultsWe extracted five IHC markers associated with overall survival (OS) and then constructed a signature in the training set (n=116) with the least absolute shrinkage and selection operator (LASSO) regression model. The validation set (n=74) was further built to confirm the prognostic significance of this classifier. We then divided patients into high- and low-risk groups according to the IHC score. In the training set, the 5-year OS rate was 22.0% (95% confidence interval [CI]: 11.2%- 43.2%) for the high-risk group and 54.1% (95% CI: 41.8%-69.9%) for the low-risk group (P<0.001), and in the validation set, the 5-year OS rate was 38.1% (95% CI: 17.9%-81.1%) for the high-risk group and 43.1% (95% CI: 30.0%-61.9%) for the low-risk group (P=0.26). Multivariable analysis revealed that IHC score, T stage, and primary tumor site were independent variables for predicting OS (all P<0.05). We developed a nomogram incorporating clinicopathological risk factors (primary site and T stage) and the IHC score to predict 3-, 5-, and 10-year OS.ConclusionsA nomogram was generated and confirmed to be of clinical value. Our IHC classifier integrating five IHC markers could help clinicians make decisions and determine optimal treatments for patients with MMHN.

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“…Published Melan-A positivity rates are considerably discordant for various tumor entities. For example, the fraction of positive tumors varies from 4% to 100% in benign nevi [8][9][10][11][12][13][14][15][16][17][18][19][20], 69%-100% in primary malignant melanoma [8-11, 13, 17, 19-33], 0%-33% in desmoplastic melanoma [8,10,11,17,20,23,31,33], 50%-81% in lymph node metastases of malignant melanoma [13,27], 50%-100% in adrenocortical carcinoma [11,[34][35][36][37][38][39], 68%-100% in adrenocortical adenoma [11,35,37,38], 50%-100% in renal angiomyolipoma [40][41][42][43][44], 0%-20% in leiomyosarcoma [10,11,25], 0%-25% in breast cancer [5,25,35,45], 0%-17% in renal cell carcinoma…”

Section: Melanocyte Antigen (Melanmentioning

confidence: 99%

“…Published Melan‐A positivity rates are considerably discordant for various tumor entities. For example, the fraction of positive tumors varies from 4% to 100% in benign nevi [8–20], 69%–100% in primary malignant melanoma [8–11, 13, 17, 19–33], 0%–33% in desmoplastic melanoma [8, 10, 11, 17, 20, 23, 31, 33], 50%–81% in lymph node metastases of malignant melanoma [13, 27], 50%–100% in adrenocortical carcinoma [11, 34–39], 68%–100% in adrenocortical adenoma [11, 35, 37, 38], 50%–100% in renal angiomyolipoma [40–44], 0%–20% in leiomyosarcoma [10, 11, 25], 0%–25% in breast cancer [5, 25, 35, 45], 0%–17% in renal cell carcinoma [5, 25, 35, 38, 46, 47] and 0%–100% in ovarian carcinomas [5, 35, 48–51]. Variable antibody properties, different staining protocols, and varying criteria for defining positivity may have caused these divergent data.…”

Section: Introductionmentioning

confidence: 99%

Staining pattern of specific and cross‐reacting Melan‐A antibodies: A comparative study on 15,840 samples from 133 human tumor types

Boroojerdi,

Weidemann,

Menz

et al. 2024

APMIS

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The Melan‐A (melanocyte antigen) protein, also termed ‘melanoma antigen recognized by T cells 1’ (MART‐1) is a protein with unknown function whose expression is specific for the melanocyte lineage. Antibodies against Melan‐A are thus used for identifying melanocytic tumors, but some Melan‐A antibodies show an additional – diagnostically useful – cross‐reactivity against an unspecified protein involved in corticosteroid hormone synthesis. To comprehensively compare the staining patterns of a specific and a cross‐reactive Melan‐A antibody in normal and neoplastic tissues, tissue microarrays containing 15,840 samples from 133 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. For the Melan‐A‐specific antibody ‘Melan‐A specific’ (MSVA‐900M), Melan‐A positivity was seen in 96.0% of 25 benign nevi, 93.0% of 40 primary and 86.7% of 75 metastatic melanomas, 82.4% of 85 renal angiomyolipomas as well as 96.4% of 84 neurofibromas, 2.2% of 46 granular cell tumors, 1.0% of 104 schwannomas, and 1.1% of 87 leiomyosarcomas. The cross‐reactive antibody ‘Melan‐A+' (MSVA‐901M+) stained 98.1% of the tumors stained by ‘Melan‐A specific’. In addition, high positivity rates were seen in sex‐cord‐stroma tumors of the ovary (35.3%–100%) and the testis (86.7%) as well as for adrenocortical neoplasms (76.3%–83.0%). Only nine further tumor groups showed Melan‐A+ staining, including five different categories of urothelial carcinomas. Our data provide a comprehensive overview on the staining patterns of specific and cross‐reactive Melan‐A antibodies. The data demonstrate that both antibodies are highly useful for their specific purpose. It is important for pathologists to distinguish these two Melan‐A antibody subtypes for their daily work.

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Diagnostic utility of dual 5‐hydroxymethylcytosine/Melan‐A immunohistochemistry in differentiating nodal nevus from metastatic melanoma: An effective first‐line test for the workup of sentinel lymph node specimen

Cited by 9 publications

References 21 publications

Standardized Computer-Assisted Analysis of 5-hmC Immunoreactivity in Dysplastic Nevi and Superficial Spreading Melanomas

Standardized Computer-Assisted Analysis of 5-hmC Immunoreactivity in Dysplastic Nevi and Superficial Spreading Melanomas

Prognostic Value of an Immunohistochemical Signature in Patients With Head and Neck Mucosal Melanoma

Staining pattern of specific and cross‐reacting Melan‐A antibodies: A comparative study on 15,840 samples from 133 human tumor types

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