p16 Expression Is Not a Surrogate Marker for High-Risk Human Papillomavirus Infection in Periocular Sebaceous Carcinoma

Stagner, Anna M.; Afrogheh, Amir; Iacob, Codrin; Grossniklaus, Hans E.; Maske, Christopher; Hiss, Donovan C.; Faquin, William C.

doi:10.1016/j.ajo.2016.07.012

Cited by 28 publications

(24 citation statements)

References 32 publications

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“…As such, prior efforts have produced conflicting results on the relationship between OA sebaceous carcinoma and HPV infection. Some studies (11,44,46) failed to confirm any relationship with HPV infection across 38 patient tumors, and a study in which a single HPV-positive case was identified by PCR for HPV DNA failed to confirm transcriptionally active HPV infection by in situ hybridization (48). These differences are partially attributable to the application of differing technologies for HPV detection, including in situ hybridization for HPV DNA or RNA or PCR for HPV DNA.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is unclear whether these latter TP53-positive tumors actually carried a somatic TP53 mutation. Of note, detection of p16 protein expression-typically a surrogate for HPV positivity in HPV-driven tumors-has not been shown to predict HPV infection in prior studies on OA sebaceous carcinoma (48). This is likely because HPV-negative OA sebaceous carcinomas harbor a high frequency inactivating RB1 mutations, and RB1 inactivation itself typically correlates with elevated levels of p16 protein expression (49).…”

Section: Discussionmentioning

confidence: 99%

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Distinct Biological Types of Ocular Adnexal Sebaceous Carcinoma: HPV-Driven and Virus-Negative Tumors Arise through Nonoverlapping Molecular-Genetic Alterations

Tetzlaff

Curry

Ning

et al. 2019

Clinical Cancer Research

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Purpose: Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy of the eyelid and ocular adnexa that frequently recurs and metastasizes, and effective therapies beyond surgical excision are lacking. There remains a critical need to define the molecular-genetic drivers of the disease to understand carcinomagenesis and progression and to devise novel treatment strategies. Experimental Design: We present next-generation sequencing of a targeted panel of cancer-associated genes in 42 and whole transcriptome RNA sequencing from eight OA sebaceous carcinomas from 29 patients. Results: We delineate two potentially distinct moleculargenetic subtypes of OA sebaceous carcinoma. The first is defined by somatic mutations impacting TP53 and/or RB1 [20/29 (70%) patients, including 10 patients whose primary tumors contained coexisting TP53 and RB1 mutations] with frequent concomitant mutations affecting NOTCH genes. These tumors arise in older patients and show frequent local recurrence. The second subtype [9/29 (31%) patients] lacks mutations affecting TP53, RB1, or NOTCH family members, but in 44% (4/9) of these tumors, RNA sequencing and in situ hybridization studies confirm transcriptionally active high-risk human papillomavirus. These tumors arise in younger patients and have not shown local recurrence. Conclusions: Together, our findings establish a potential molecular-genetic framework by which to understand the development and progression of OA sebaceous carcinoma and provide key molecular-genetic insights to direct the design of novel therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Distinct Biological Types of Ocular Adnexal Sebaceous Carcinoma: HPV-Driven and Virus-Negative Tumors Arise through Nonoverlapping Molecular-Genetic Alterations

Tetzlaff

Curry

Ning

et al. 2019

Clinical Cancer Research

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“…The varied origin of this neoplasm highlights the importance of considering sebaceous carcinoma regardless of the anatomical location [ 16 ]. Several papers have been published on the relationship between sebaceous cancer and human papillomavirus [ 17 , 18 ]. Overexpression of p53 is involved in the carcinogenesis of this tumor, and is a risk factor suggesting a poor prognosis [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Sebaceous carcinoma arising from sebaceoma

Lee

Kwak

Kim

et al. 2021

Arch Craniofac Surg

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“…[1][2][3][4][5][6][7] Whereas immunohistochemical techniques for expression of adipophilin, epithelial membrane antigen (EMA), BerEP4 and several other markers are well established in the differential diagnosis of sebaceous gland tumors, [8][9][10][11][12][13][14][15][16][17][18] our information about the exact cellular architecture of these lesions and even of the normal sebaceous gland is still scarce. [1][2][3][4][5][6][7] Whereas immunohistochemical techniques for expression of adipophilin, epithelial membrane antigen (EMA), BerEP4 and several other markers are well established in the differential diagnosis of sebaceous gland tumors, [8][9][10][11][12][13][14][15][16][17][18] our information about the exact cellular architecture of these lesions and even of the normal sebaceous gland is still scarce.…”

Section: Introductionmentioning

confidence: 99%

“…Sebaceous tumors are uncommon adnexal tumors. [1][2][3][4][5][6][7] Whereas immunohistochemical techniques for expression of adipophilin, epithelial membrane antigen (EMA), BerEP4 and several other markers are well established in the differential diagnosis of sebaceous gland tumors, [8][9][10][11][12][13][14][15][16][17][18] our information about the exact cellular architecture of these lesions and even of the normal sebaceous gland is still scarce. [19][20][21][22] Furthermore, the histogenesis of extraocular sebaceous carcinomas is, in contrast to ocular sebaceous carcinomas, still unclear.…”

Section: Introductionmentioning

confidence: 99%

Spatial analysis of p63, K5 and K7 defines two groups of progenitor cells that differentially contribute to the maintenance of normal sebaceous glands, extraocular sebaceous carcinoma and benign sebaceous tumors

Boecker

Reusch

Mielke

et al. 2019

The Journal of Dermatology

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The histogenesis of extraocular sebaceous carcinomas is – in contrast to ocular sebaceous carcinomas – unclear, and information about the exact cellular architecture of these lesions and even of the normal sebaceous gland is still scarce. This study attempts to elucidate the histogenesis of sebaceous tumors, using multicolor immunofluorescence stainings to analyze 21 cases of sebaceous tumors (six each of extraocular sebaceous carcinoma, sebaceous adenoma and sebaceoma, and three cases of steatocystomas) and eight cases of normal sebaceous glands for p63, several keratins, androgen receptor, adipophilin, epithelial membrane antigen (EMA) and Ki‐67. The data of this observational study provide evidence for the existence of two subpopulations of progenitors in normal sebaceous glands: (i) p63+ K5+ progenitors which generate the K10+ luminal cells of sebaceous ducts; and (ii) p63+ K5+ K7+ progenitors which finally generate K7+ adipophilin+ EMA+ sebocytes. Without exception, all types of sebaceous tumors contained p63+ K5+ cells. Furthermore, these tumors showed a cellular hierarchy and differentiation to adipophilin+ and/or EMA+ mature sebocytes and to K10+ ductal cells through intermediary cells. Notably, a considerable number of sebaceous tumors lack the K7 pathway of cell maintenance in the normal sebaceous lobule. Based on our data, we propose a cellular algorithmic model of the hierarchy of normal sebaceous glands and of sebocytic tumors in which p63+ K5+ cells play a major role.

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p16 Expression Is Not a Surrogate Marker for High-Risk Human Papillomavirus Infection in Periocular Sebaceous Carcinoma

Cited by 28 publications

References 32 publications

Distinct Biological Types of Ocular Adnexal Sebaceous Carcinoma: HPV-Driven and Virus-Negative Tumors Arise through Nonoverlapping Molecular-Genetic Alterations

Distinct Biological Types of Ocular Adnexal Sebaceous Carcinoma: HPV-Driven and Virus-Negative Tumors Arise through Nonoverlapping Molecular-Genetic Alterations

Sebaceous carcinoma arising from sebaceoma

Spatial analysis of p63, K5 and K7 defines two groups of progenitor cells that differentially contribute to the maintenance of normal sebaceous glands, extraocular sebaceous carcinoma and benign sebaceous tumors

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