Squamous Cell Carcinoma in Patients with Recessive Dystrophic Epidermolysis Bullosa - A Literature Review
No Thumbnail Available
Date
2022
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Rīgas Stradiņa universitāte
Rīga Stradiņš University
Rīga Stradiņš University
Abstract
Šajā pētnieciskajā darbā, kas veidots kā literatūras apskats, uzmanība pievērsta recesīvās distrofiskās epidermolīzes bullozes etioloģijai un tās saiknei ar ādas plakanšūnu karcinomas veidošanos. Var secināt, ka COL7A1 gēna mutācijas ir atbildīgas par recesīvās distrofiskās epidermolīzes bullozes attīstību. Izpētot dažādas molekulārās preferences, t. i., pazīmes, ir pierādīts, ka ādas plakanšūnu karcinomas etioloģija pacientiem ar recesīvo distrofisko epidermolīzi bullozi spilgti atšķiras no tās, kas novērota vispārējā populācijā. Neatkarīgi no slimības apakšgrupas VII kolagēna mutācijas atspoguļo molekulārās izmaiņas bazālajā membrānā un enkuro filamentos, veidojot mikrovidi, kas ir tendēta uz audzēju veidošanos. Tādējādi atšķirībā no vispārējās populācijas šīs ģenētiskās izmaiņas, kas novērotas pacientiem ar recesīvo distrofisko epidermolīzi bullozi, rada ievērojami paaugstinātu kumulatīvo ādas plakanšūnu karcinomas risku. Turklāt hronisku brūču un bakteriālu superinfekciju lielā biežuma dēļ ādas izmaiņas liecina, ka ļaundabīgie procesi tiek atklāti vēlāk nekā vispārējā populācijā. Tas apgrūtina ķirurģisko izgriešanu, kur var iegūt skaidras robežas. Galīgais rezultāts ir agresīvs ādas ļaundabīgs audzējs ar augstu recidīvu un metastāžu biežumu.
Pēc šiem atklājumiem tiek pielāgotas jaunas ārstēšanas metodes. Neatkarīgi no terapeitiskā līdzekļa un ārstēšanas metodes mērķis ir vērsties pret pamatā esošo etioloģiju vai recesīvo distrofisko epidermolīzi bullozi, stimulēt iedzimto imunitāti un/vai aktivizēt audzēja izdzīvošanai nelabvēlīgas strukturālās izmaiņas. Veicinot funkcionālā VII kolagēna sintēzi, tiek mēģināts samazināt un optimālos gadījumos likvidēt izmainīto mikrovidi. Līdz šā raksta publicēšanas dienai iegūtie rezultāti ir ierobežoti, bet daudzsološi. Tā kā pētniecības lauks ir neliels un klīniskie pētījumi ir agrīnā stadijā, pašreizējās ilgtermiņa rezultātu iespējas vēl nav zināmas. Tāpēc, pirms izstrādāt jaunas vadlīnijas ar uzlabotiem terapeitiskajiem standartiem, kas šiem pacientiem dotu cerību uz labāku izdzīvošanu un mazākām ciešanām, būtu jāveic turpmāki izmēģinājumi un pētījumi.
This research paper formed as a literature review focuses on the etiology of recessive dystrophic epidermolysis bullosa and its connection to the formation of cutaneous squamous cell carcinoma. It can be concluded that mutations in the COL7A1 gene are responsible for the development of recessive dystrophic epidermolysis bullosa. By studying different molecular preferences i.e. signatures, it has been proved that the etiology of cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa is vividly different from the one seen in the general population. Regardless of the disease subgroup, mutations of collagen VII reflect molecular changes in the basement membrane and anchoring filaments, forming a microenvironment prone to tumorigenesis. Thus, in contrast to the general population, these genetic changes seen in patients with recessive dystrophic epidermolysis bullosa result in a markedly elevated cumulative risk for cutaneous squamous cell carcinoma. Furthermore, due to a high rate of chronic wounds and bacterial superinfections, the skin changes suggest malignant processes are detected later than in the general population. This complicates the performance of surgical excisions where clear borders can be obtained. The ultimate outcome is an aggressive cutaneous malignancy with a high rate of recurrence and metastasis. Upon these discoveries, new treatment methods are being adapted. Regardless of the therapeutic agent and modality, the aim is to target the underlying etiology or recessive dystrophic epidermolysis bullosa, stimulate the innate immunity, and/or activate structural changes which are unfavorable for tumor survival. By inducing the synthesis of functional collagen VII, an approach is made to minimize, and in optimal cases eliminate the altered microenvironment. Until the publication date of this paper, the findings are limited but promising. Because of a small research field and clinical trials being in their early phases, the current possibilities for long-term outcomes are still unknown. Hence, prior to establishing new guidelines with improved therapeutic standards that bring hope for better survival and less suffering for these patients, further trials and studies should be conducted.
This research paper formed as a literature review focuses on the etiology of recessive dystrophic epidermolysis bullosa and its connection to the formation of cutaneous squamous cell carcinoma. It can be concluded that mutations in the COL7A1 gene are responsible for the development of recessive dystrophic epidermolysis bullosa. By studying different molecular preferences i.e. signatures, it has been proved that the etiology of cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa is vividly different from the one seen in the general population. Regardless of the disease subgroup, mutations of collagen VII reflect molecular changes in the basement membrane and anchoring filaments, forming a microenvironment prone to tumorigenesis. Thus, in contrast to the general population, these genetic changes seen in patients with recessive dystrophic epidermolysis bullosa result in a markedly elevated cumulative risk for cutaneous squamous cell carcinoma. Furthermore, due to a high rate of chronic wounds and bacterial superinfections, the skin changes suggest malignant processes are detected later than in the general population. This complicates the performance of surgical excisions where clear borders can be obtained. The ultimate outcome is an aggressive cutaneous malignancy with a high rate of recurrence and metastasis. Upon these discoveries, new treatment methods are being adapted. Regardless of the therapeutic agent and modality, the aim is to target the underlying etiology or recessive dystrophic epidermolysis bullosa, stimulate the innate immunity, and/or activate structural changes which are unfavorable for tumor survival. By inducing the synthesis of functional collagen VII, an approach is made to minimize, and in optimal cases eliminate the altered microenvironment. Until the publication date of this paper, the findings are limited but promising. Because of a small research field and clinical trials being in their early phases, the current possibilities for long-term outcomes are still unknown. Hence, prior to establishing new guidelines with improved therapeutic standards that bring hope for better survival and less suffering for these patients, further trials and studies should be conducted.
Description
Medicīna
Medicine
Veselības aprūpe
Health Care
Medicine
Veselības aprūpe
Health Care
Keywords
epidermolysis bullosa, recessive dystrophic epidermolysis bullosa, epidermolysis bullosa hallopeau-siemens, squamous cell carcinoma, COL7A1, collagen VII, TGF-β, TGF-α, APOBEC, High mobility group box 1, bazālās membrānas zona, ar vēzi saistīti fibroblasti, laminīns 332, epidermolysis bullosa, recessive dystrophic epidermolysis bullosa, epidermolysis bullosa hallopeau-siemens, squamous cell carcinoma, COL7A1, collagen VII, TGF-β, TGF-α, APOBEC, High mobility group box 1, basement membrane zone”, “cancer associated fibroblasts, laminin 332