Carcinoma-like vascular density in atypic keratoacanthoma suggests malignant progression

Strieth, Sebastian; Hartschuh, Wolfgang; Pilz, Lothar R.; Fusenig, Norbert E.

doi:10.1038/sj.bjc.6600622

Cited by 7 publications

(9 citation statements)

References 42 publications

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“…It has been showed that increasing of reactive oxygen and nitrogen species could also induce expression of a variety of cancer associated gens including the tumor necrosis factor gene (TNF), matrix metalloproteinases (MMP) genes, and vascular endothelial growth factor (VEGF) genes. Up regulation of these genes could affect on cell migration and angiogenesis via regulation of Nuclear Factor ĸB (NFĸB) …”

Section: Introductionmentioning

confidence: 99%

Oral tumors in children: Diagnosis and management

Khanmohammadi

Mir

Baniebrahimi

et al. 2017

J of Cellular Biochemistry

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Oral tumors are one of important tumors which could be associated with serious problems in infant and children. It has been showed that a variety of cellular and molecular pathways including genetics and epigenetics mechanisms (eg, chromosomal alterations, and microRNA) involved in pathogenesis events present in oral tumors. Identification of these pathways could contribute to better treatment of oral tumor patients. Early detection is one of key steps in management of oral tumors which could contribute to improve clinical outcomes and better treatment of infant with oral tumors. Despite of easy accession of the oral cavity, oral tumors (malign/benign) are diagnosed in advance stages. Therefore, these tumors indicate a poor survival rate. It has been showed that various approaches including imaging techniques, chemical, genetics, and epigenetic biomarkers could have critical roles in early detection of oral tumors. Treatment of oral tumors is associated with employing of various therapeutic approaches including surgery, chemotherapy, and radiation. Data on effective diagnostic platforms and therapeutic approaches for oral tumors in children and infant are rare. We offer that a variety of biomarkers such as microRNAs which could be used for oral tumors in adults may be good candidates for early detection of oral tumors in children. Here, we summarized various aspects of oral tumors in children such as molecular pathways, diagnosis, and management of them.

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Section: Introductionmentioning

confidence: 99%

Oral tumors in children: Diagnosis and management

Khanmohammadi

Mir

Baniebrahimi

et al. 2017

J of Cellular Biochemistry

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“…The real nature of this neoplasma and its relationship to squamous cell carcinoma (SCC) have been disputed for a long time. Some authors consider KA as a benign neoplasia, others as a precursor of SCC, 2 others as a well-differentiated variant of cutaneous SCCs 3 or at least an abortive malignancy that only rarely progresses into an invasive SCC. 4 Differential diagnosis between KA and SCC is challenging due to their similarities and the lack of reliable diagnostic criteria to distinguish both entities.…”

Section: Introductionmentioning

confidence: 99%

Keratoacanthoma and Keratoacanthoma-Like Squamous Cell Carcinoma

et al. 2015

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Differential diagnosis between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is difficult due to their similarities. The mechanisms that drive their distinct biological behavior are poorly understood.To investigate whether the assessment of microvessel density (MVD) could be helpful in KA and SCC differential diagnosis and to gain insight into the pathogenesis of KA-like neoplasms, we compared the density of CD105- and CD34-stained vessels in KAs and SCCs and their relation to the expression of the p53 oncoprotein and proliferation marker Ki67.This is an observational retrospective cohort study. Forty lesions with clinical appearance of KAs (29 KAs and 11 SCCs) entered the study. A biopsy was taken from each lesion at presentation and the natural clinical course was monitored for at least 1 month. Growing or minimally regressing lesions were submitted to complete surgical excision. The diagnoses were established on combined clinical, histological, and follow-up evaluations. The MVD and p53 or Ki67 expression in neoplastic cells were assessed through morphometry.The MVD did not show discriminating power between KAs and SCCs. The Ki67 proliferation rate was significantly higher in SCCs. Although neoangiogenesis (CD105-MVD) in KAs was associated with cell proliferation, in SCCs it was not. There was significant correlation between p53 expression and neoplasia size in SCCs but not in KAs.From our results, we may conclude that KA and SCC have similarities, as CD105- and CD34-MVD. However, the low Ki67 proliferation index and the positive correlation between Ki-67 index and neovascularization in KA suggest a dependence in neovascularization to grow in KA, pointing to involvement of distinct pathogenesis.

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“…4 It is thought that those keratoacanthomas of sun-exposed locations and diagnosed in older patients may more frequently progress to SCC. 5 Some authors believe that keratoacanthoma is a well-differentiated variant of SCC representing a range of neoplastic activity with no clear distinction, whereas some authors consider the histological and cytological differentiation precise, sure, and possible. 1,[5][6][7] Thus, the natural behavior of keratoacanthomas remains unclear and controversial, and practically all these tumors are currently surgically excised.…”

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confidence: 99%

“…5 Some authors believe that keratoacanthoma is a well-differentiated variant of SCC representing a range of neoplastic activity with no clear distinction, whereas some authors consider the histological and cytological differentiation precise, sure, and possible. 1,[5][6][7] Thus, the natural behavior of keratoacanthomas remains unclear and controversial, and practically all these tumors are currently surgically excised. 3 In addition to the proportion of cells with atypia, one malignancy-associated criterion in keratoacanthomas is increased microvessel density.…”

mentioning

confidence: 99%

“…3 In addition to the proportion of cells with atypia, one malignancy-associated criterion in keratoacanthomas is increased microvessel density. 5 Matrix metalloproteinases (MMPs), a family of 23 human zinc-dependent proteolytic enzymes, have been implicated at all stages of tumorigenesis. 8 They mediate apoptosis, proliferation, and differentiation, tumor angiogenesis, and malignant conversion 9 by degrading basement membranes and various matrix components as well as by activating chemokines and growth factors.…”

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confidence: 99%

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Transformation-specific matrix metalloproteinases, MMP-7 and MMP-13, are present in epithelial cells of keratoacanthomas

et al. 2006

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Keratoacanthomas are rapidly growing hyperproliferative skin tumors that may clinically or histologically be difficult to distinguish from well-differentiated squamous cell cancers (SCCs). UV light, trauma, and immune suppression represent their etiological factors. As matrix metalloproteinases (MMPs) are implicated at all stages of tumorigenesis, we investigated the expression profile of several cancer-related MMPs to find markers that would differentiate keratoacanthomas from SCCs and shed light to the pathobiology of keratoacanthoma. Samples from 31 keratoacanthomas and 15 grade I SCCs were studied using immunohistochemistry for MMP-2, -7, -8, -9, -10, -13, and -19 and p16 and laminin-5c2 chain. In situ hybridization for MMP-7, -10, and -13 was performed in a subset of tumors. Keratinocytes with atypia, presence of neovascularization, and composition of the inflammatory infiltrate were graded from hematoxylin-eosin stainings. MMP-7 was present in the epithelium of 4/31 keratoacanthomas and 9/15 SCCs, MMP-8 in 3/30 keratoacanthomas and 0/15 SCCs, but MMP-13 in 16/31 keratoacanthomas and 10/15 SCCs, and MMP-10 in 28/31 keratoacanthomas and all cancers. MMP-9 was detected in the epithelium in 5/31 keratoacanthomas and 8/15 SCCs, whereas MMP-2 was only present in fibroblasts in both tumors. MMP-19 was upregulated in proliferating epithelium of keratoacanthomas as was p16. Cytoplasmic laminin-5c2 was particularly abundant in keratinocytes at the pushing border of MMP-13-positive keratoacanthomas. We conclude that although some MMPs (MMP-10 and -13) are abundantly expressed in keratoacanthomas, the presence of MMP-7 and -9 in their epithelial pushing border is rare and should raise suspicion of SCC. Further, the loss of MMP-19 and p16 could aid in making the differential diagnosis between well-differentiated SCC and keratoacanthoma. Frequent expression of the transformationspecific MMP-13 in keratoacanthomas suggests that they are not benign tumors but incomplete SCCs.

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Carcinoma-like vascular density in atypic keratoacanthoma suggests malignant progression

Cited by 7 publications

References 42 publications

Oral tumors in children: Diagnosis and management

Oral tumors in children: Diagnosis and management

Keratoacanthoma and Keratoacanthoma-Like Squamous Cell Carcinoma

Transformation-specific matrix metalloproteinases, MMP-7 and MMP-13, are present in epithelial cells of keratoacanthomas

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