Loss of ZNF750 in ocular and cutaneous sebaceous carcinoma

North, Jeffrey P.; Solomon, David A.; Golovato, Justin; Bloomer, Michelle; Benz, Stephen C.; Cho, Raymond J.

doi:10.1111/cup.13516

Cited by 7 publications

(5 citation statements)

References 16 publications

(25 reference statements)

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“…Loss of expression of ZNF750 was detected exclusively in a subset of SC compared with benign sebaceous proliferations. 20 However, its specificity is uncertain because it has been reported that ZNF750 acts as a tumor suppressor in a variety of SCCs. 21 The potential difficulty in the recognition of basaloid SC arises not only because of the morphologic overlap with other cutaneous basaloid neoplasms, but also because of the nonspecific immunohistochemical profile of many of the entities in the differential diagnosis.…”

Section: Discussionmentioning

confidence: 99%

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Androgen Receptor Immunohistochemistry is Superior to PRAME for the Differentiation of Sebaceous Carcinoma From Primary Cutaneous Basaloid Mimics

Wakefield,

Russell-Goldman

2023

The American Journal of Dermatopathology

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Cutaneous sebaceous neoplasia comprises a spectrum of disease ranging from benign adenomas to malignant carcinomas. The hallmark of these lesions is sebaceous differentiation. However, poorly-differentiated sebaceous carcinoma (SC), which lacks significant overt sebaceous differentiation, can show morphologic overlap with a variety of other basaloid cutaneous neoplasms. The accurate classification of SC is essential not only for diagnosis, but also because of the potential association with Muir-Torre syndrome. Androgen receptor (AR) is a sensitive, but not entirely specific immunohistochemical marker that has been used for the diagnosis of SC. PReferentially expressed Antigen in MElanoma (PRAME) demonstrates strong cytoplasmic labeling of mature sebocytes and has been reported to be expressed in a variety of sebaceous neoplasms, including in the basaloid cell component. Therefore, we sought to compare the diagnostic use of cytoplasmic PRAME expression with that of AR for the distinction of SC from a cohort of basaloid cutaneous mimics; namely basal cell carcinoma, basaloid squamous cell carcinoma, pilomatricoma, cutaneous lymphadenoma, and extra-mammary Paget disease. We report that cytoplasmic PRAME expression is uncommon in poorly differentiated SC, and although specific, it shows very low sensitivity (22%). In contrast, AR was moderately sensitive (66%) and highly specific (92%) for the distinction of SC from basaloid mimics. These attributes, in addition to the nuclear expression of AR in the sebocytic and basaloid components of SC, suggest that AR is superior to PRAME for the diagnosis of SC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Androgen Receptor Immunohistochemistry is Superior to PRAME for the Differentiation of Sebaceous Carcinoma From Primary Cutaneous Basaloid Mimics

Wakefield,

Russell-Goldman

2023

The American Journal of Dermatopathology

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“…The different expression pattern of beta‐catenin, LEF1, and Shh in ocular and extraocular SC may result from intrinsic differences of these two types of SC. For example, ZNF750, which controls epithelial homeostasis by regulating epidermal differentiation, was also differentially expressed in ocular and extraocular SC 22 …”

Section: Discussionmentioning

confidence: 99%

“…For example, ZNF750, which controls epithelial homeostasis by regulating epidermal differentiation, was also differentially expressed in ocular and extraocular SC. 22 The aberrant hedgehog signaling and LEF1 loss-of-function in carcinogenesis of extraocular SC may not be exclusively independent. In fact, there is evidence of interaction between Wnt/beta-catenin and hedgehog signaling.…”

Section: Impaired Wnt/beta-catenin and Ptch Signaling In Extracutaneo...mentioning

confidence: 99%

Impaired Wnt/beta‐catenin and protein patched homolog 1 signaling in extraocular sebaceous carcinoma: A clinical and histopathological study

Cheng

Lan

Lee

2022

The Journal of Dermatology

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Sebaceous carcinoma (SC) is a rare malignant neoplasm with sebaceous differentiation.SC is classified into eyelid and extraocular SC clinically. Most studies have focused on the eyelid SC in terms of pathogenesis, treatment, and prognosis. In skin, Wnt/beta-catenin and hedgehog signaling are two major pathways in sebaceous differentiation. We aimed to characterize the clinical and histopathological features of extraocular SC and to measure the expression of beta-catenin, lymphoid enhancer-binding factor 1 (LEF1), sonic hedgehog (Shh), and protein patched homolog 1 (PTCH) in extraocular SC. Ten cases of extraocular SC were identified from 2007 to 2020. The clinical features, microscopic findings, and prognosis were analyzed. Immunohistochemical stain for beta-catenin, LEF1, Shh, and PTCH were performed in extraocular SC and other benign sebaceous tumors including sebaceous hyperplasia, sebaceous adenoma, and sebaceoma. The male:female ratio was 4:6. The median onset age was 73.5 years (range, 43-88). Seven patients out of 10 were diagnosed after 60 years. Most extraocular SC were located on the head and neck with indurated plaque. Two patients had concurrent internal cancers and three patients showed lymph node metastasis at time of presentation. Five-year overall-survival was 40%. Beta-catenin was expressed membranously in all sebaceous hyperplasia, but was expressed variably in extraocular SC (1/5). While LEF1 was unequivocally expressed in normal hair follicles, LEF1 expression was absent in all extraocular SC and benign sebaceous tumors. Regarding the sonic hedgehog signaling, Shh and PTCH were all expressed in the cytoplasm of sebaceous hyperplasia, sebaceous adenoma, and sebaceoma. In contrast, PTCH was absent in all cases of extraocular SC and only 50% of the extraocular SC expressed cytoplasmic Shh. To conclude, extraocular SC commonly affects facial skin in the elderly. Inactivated Wnt/beta-catenin and aberrant hedgehog pathway may contribute to the carcinogenesis of extraocular SC. Further studies may be required to elucidate the causative mechanism of these pathways in extraocular SC.

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“…Two other commonly mutated genes in SGC are ZNF750 [14], particularly in the aforementioned pauci-mutational group, and PCDH15 [13], significantly associated with nodal and distant metastasis.…”

Section: Introductionmentioning

confidence: 99%

Base-Excision Repair Mutational Signature in Two Sebaceous Carcinomas of the Eyelid

Sangiorgi,

Giannuzzi,

Molinario

et al. 2023

Genes

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Personalized medicine aims to develop tailored treatments for individual patients based on specific mutations present in the affected organ. This approach has proven paramount in cancer treatment, as each tumor carries distinct driver mutations that respond to targeted drugs and, in some cases, may confer resistance to other therapies. Particularly for rare conditions, personalized medicine has the potential to revolutionize treatment strategies. Rare cancers often lack extensive datasets of molecular and pathological information, large-scale trials for novel therapies, and established treatment guidelines. Consequently, surgery is frequently the only viable option for many rare tumors, when feasible, as traditional multimodal approaches employed for more common cancers often play a limited role. Sebaceous carcinoma of the eyelid is an exceptionally rare cancer affecting the eye’s adnexal tissues, most frequently reported in Asia, but whose prevalence is significantly increasing even in Europe and the US. The sole established curative treatment is surgical excision, which can lead to significant disfigurement. In cases of metastatic sebaceous carcinoma, validated drug options are currently lacking. In this project, we set out to characterize the mutational landscape of two sebaceous carcinomas of the eyelid following surgical excision. Utilizing available bioinformatics tools, we demonstrated our ability to identify common features promptly and accurately in both tumors. These features included a Base-Excision Repair mutational signature, a notably high tumor mutational burden, and key driver mutations in somatic tissues. These findings had not been previously reported in similar studies. This report underscores how, in the case of rare tumors, it is possible to comprehensively characterize the mutational landscape of each individual case, potentially opening doors to targeted therapeutic options.

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Loss of ZNF750 in ocular and cutaneous sebaceous carcinoma

Cited by 7 publications

References 16 publications

Androgen Receptor Immunohistochemistry is Superior to PRAME for the Differentiation of Sebaceous Carcinoma From Primary Cutaneous Basaloid Mimics

Androgen Receptor Immunohistochemistry is Superior to PRAME for the Differentiation of Sebaceous Carcinoma From Primary Cutaneous Basaloid Mimics

Impaired Wnt/beta‐catenin and protein patched homolog 1 signaling in extraocular sebaceous carcinoma: A clinical and histopathological study

Base-Excision Repair Mutational Signature in Two Sebaceous Carcinomas of the Eyelid

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