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The aim of this study is to collect sebaceous carcinomas from the Fondazione Policlinico Gemelli retrospectively and prospectively, to analyse them morphologically and immunopathologically and to correlate them with molecular genetic aspects. This study will help to clarify and develop a more effective multidisciplinary diagnostic-therapeutic pathway.
The purpose of this research is to prospectively and retrospectively collect sebaceous carcinomas from the Fondazione Policlinico Gemelli, examine them immunopathologically and morphologically, and establish a correlation between these characteristics and molecular genetic factors. Conducting this research will contribute to the elucidation and advancement of a multidisciplinary therapeutic-diagnostic pathway. The study will utilise surgical specimens, irrespective of the disease stage, that have been formalin-fixed and paraffin-embedded. These specimens were previously collected for clinical practise at the Ocular Oncology of Fondazione Policlinico A. Gemelli IRCCS The informed consent of the patients regarding the use of these specimens for research purposes was obtained beforehand.Each specimen will be subjected to a comprehensive microscopic examination, followed by precise subclassification in accordance with the WHO classification and immunophenotypic characterization. An exhaustive collection of conventionally standardised histopathological prognostic attributes for sebaceous carcinomas will be compiled. Following this, tissue samples are sent for single and/or multiple IHC. Tumour tissues will be subjected to automated digital quantification in conjunction with multiparametric cell line evaluation. Integrating IHC with digital automation of analysis.Exome sequencing will be performed on DNA extracted from paraffin-embedded sections in order to detect variants that are specific to tumours.
For each tumour, three to nine sections (10 micrometres in thickness) will be utilised as the DNA source. Following the identification and separation of tumour tissue from normal tissue by the pathologist, the two DNAs will be sequenced independently. A comparison will be made between variants derived from tumour and normal tissue, with contrasting results. Anticipated outcomes include 1) somatic or tumor-specific variants, which are non-existent in healthy tissue, and 2) variants that are lost during the evolution of the tumour as a result of segmental chromosomal deletion or other mechanisms that induce heterozygosity loss. During the project's prospective phase, newly developed tumours will be preserved. Furthermore, this resource will facilitate methylome analysis, which is in addition to exome analysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients diagnosed with Ca sebaceous of the ocular adnexa. | Experimental | adult patients diagnosed with Ca sebaceous of the ocular adnexa. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| exome sequencing (retrospective) and exome and methylome sequencing (prospective) | Genetic | Three to nine sections will be used as the source of DNA for each tumor. The pathologist will identify and separate tumor tissue from normal tissue, and the two DNAs will be sequenced separately. Variants obtained from tumor and normal tissue will be compared, with different outcomes. Expected in this way are 1) somatic/tumor-specific variants (which are absent in normal tissue), 2) variants lost during tumor evolution due to segmental chromosomal deletion or other mechanisms that cause loss of heterozygosity. Using these two classes of variants, a clustering analysis will be performed at the end of the sequencing project to better define the phenotype and molecular "signature" of the tumors. In the prospective part of the project, the new tumors will be frozen fresh. This resource will allow methyloma analysis to be performed. |
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of different molecules in Microscopic and immunophenotypic analysis | Tissue samples will then be sent for single and/or multiple immunohistochemistry. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of somatic variants, variants with loss of heterozygosity, global mutational signature and identification of probable driver mutations | Rate of somatic variants, variants with loss of heterozygosity, global mutational signature and identification of probable driver mutations by exome sequencing; | 1 year |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gustavo Savino | Recruiting | Roma | Rome | 00168 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27218789 | Background | Prieto-Granada C, Rodriguez-Waitkus P. Sebaceous Carcinoma of the Eyelid. Cancer Control. 2016 Apr;23(2):126-32. doi: 10.1177/107327481602300206. | |
| 31797796 | Background | Owen JL, Kibbi N, Worley B, Kelm RC, Wang JV, Barker CA, Behshad R, Bichakjian CK, Bolotin D, Bordeaux JS, Bradshaw SH, Cartee TV, Chandra S, Cho NL, Choi JN, Council ML, Demirci H, Eisen DB, Esmaeli B, Golda N, Huang CC, Ibrahim SF, Jiang SB, Kim J, Kuzel TM, Lai SY, Lawrence N, Lee EH, Leitenberger JJ, Maher IA, Mann MW, Minkis K, Mittal BB, Nehal KS, Neuhaus IM, Ozog DM, Petersen B, Rotemberg V, Samant S, Samie FH, Servaes S, Shields CL, Shin TM, Sobanko JF, Somani AK, Stebbins WG, Thomas JR, Thomas VD, Tse DT, Waldman AH, Wong MK, Xu YG, Yu SS, Zeitouni NC, Ramsay T, Reynolds KA, Poon E, Alam M. Sebaceous carcinoma: evidence-based clinical practice guidelines. Lancet Oncol. 2019 Dec;20(12):e699-e714. doi: 10.1016/S1470-2045(19)30673-4. |
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| ID | Term |
|---|---|
| D000073359 | Exome Sequencing |
| D012189 | Retrospective Studies |
| D059472 | Exome |
| D008137 | Longitudinal Studies |
| ID | Term |
|---|---|
| D000073336 | Whole Genome Sequencing |
| D017422 | Sequence Analysis, DNA |
| D017421 | Sequence Analysis |
| D005821 | Genetic Techniques |
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Single-centre interventional study on biological sample
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|
| Rate of correlations histopathological features with tumour DNA variants and disease stage. |
Rate of correlations between histopathological features with tumour DNA variants and disease stage. |
| 2 years |
| 36330713 | Background | Alfaar AS, Suckert CN, Rehak M, Girbardt C. The epidemiology of adults' eyelid malignancies in Germany between 2009 and 2015; An analysis of 42,710 patients' data. Eur J Ophthalmol. 2022 Nov 4;33(2):11206721221125018. doi: 10.1177/11206721221125018. Online ahead of print. |
| 22267270 | Background | Tryggvason G, Bayon R, Pagedar NA. Epidemiology of sebaceous carcinoma of the head and neck: implications for lymph node management. Head Neck. 2012 Dec;34(12):1765-8. doi: 10.1002/hed.22009. Epub 2012 Jan 20. |
| 24969841 | Background | Gauthier AS, Campolmi N, Tumahai P, Kantelip B, Delbosc B. Sebaceous carcinoma of the eyelid and Muir-Torre syndrome. JAMA Ophthalmol. 2014 Aug;132(8):1025-8. doi: 10.1001/jamaophthalmol.2014.1026. No abstract available. |
| 31821583 | Background | Ferreira I, Wiedemeyer K, Demetter P, Adams DJ, Arends MJ, Brenn T. Update on the pathology, genetics and somatic landscape of sebaceous tumours. Histopathology. 2020 Apr;76(5):640-649. doi: 10.1111/his.14044. Epub 2020 Mar 17. |
| 25595178 | Background | Jagan L, Zoroquiain P, Bravo-Filho V, Logan P, Qutub M, Burnier MN Jr. Sebaceous adenomas of the eyelid and Muir-Torre Syndrome. Br J Ophthalmol. 2015 Jul;99(7):909-13. doi: 10.1136/bjophthalmol-2014-305873. Epub 2015 Jan 16. |
| 3940100 | Background | Yeatts RP, Waller RR. Sebaceous carcinoma of the eyelid: pitfalls in diagnosis. Ophthalmic Plast Reconstr Surg. 1985;1(1):35-42. doi: 10.1097/00002341-198501000-00006. |
| 29985175 | Background | Orr CK, Yazdanie F, Shinder R. Current review of sebaceous cell carcinoma. Curr Opin Ophthalmol. 2018 Sep;29(5):445-450. doi: 10.1097/ICU.0000000000000505. |
| 35932255 | Background | Kumar T, Tewari P, Khanna N, Surabhi, Bharti S, Sinha R, Bhadani PP. Cytomorphology of sebaceous carcinoma of the eyelid: A short series of three cases with literature review. Diagn Cytopathol. 2022 Dec;50(12):E361-E366. doi: 10.1002/dc.25029. Epub 2022 Aug 6. |
| 30420449 | Background | Tetzlaff MT, Curry JL, Ning J, Sagiv O, Kandl TL, Peng B, Bell D, Routbort M, Hudgens CW, Ivan D, Kim TB, Chen K, Eterovic AK, Shaw K, Prieto VG, Yemelyanova A, Esmaeli B. Distinct Biological Types of Ocular Adnexal Sebaceous Carcinoma: HPV-Driven and Virus-Negative Tumors Arise through Nonoverlapping Molecular-Genetic Alterations. Clin Cancer Res. 2019 Feb 15;25(4):1280-1290. doi: 10.1158/1078-0432.CCR-18-1688. Epub 2018 Nov 12. |
| 31896805 | Background | McGrath LA, Currie ZI, Mudhar HS, Tan JHY, Salvi SM. Management of recurrent sebaceous gland carcinoma. Eye (Lond). 2020 Sep;34(9):1685-1692. doi: 10.1038/s41433-019-0756-9. Epub 2020 Jan 2. |
| 36356187 | Background | Magazin M, Dalvin LA, Salomao DR, Castner NB, Halbach C, Tooley AA. Sebaceous Carcinoma of the Eyelid: Proposed Nomenclature for Multifocal and Multicentric Disease. Ophthalmic Plast Reconstr Surg. 2023 Mar-Apr 01;39(2):117-122. doi: 10.1097/IOP.0000000000002281. Epub 2022 Oct 20. |
| D008919 |
| Investigative Techniques |
| D016022 | Case-Control Studies |
| D016021 | Epidemiologic Studies |
| D016020 | Epidemiologic Study Characteristics |
| D004812 | Epidemiologic Methods |
| D015331 | Cohort Studies |
| D017531 | Health Care Evaluation Mechanisms |
| D011787 | Quality of Health Care |
| D017530 | Health Care Quality, Access, and Evaluation |
| D011634 | Public Health |
| D004778 | Environment and Public Health |
| D016678 | Genome |
| D040342 | Genetic Structures |
| D055614 | Genetic Phenomena |