{"id":2450,"date":"2022-10-26T09:15:58","date_gmt":"2022-10-26T07:15:58","guid":{"rendered":"https:\/\/www.newslab.sk\/vysetrenie-expresie-mmr-proteinov-v-nadoroch-endometria-imunohistochemicky-je-vhodny-sposob-primarnej-selekcie-potencialnych-pripadov-s-lynchovym-syndromom\/"},"modified":"2022-10-26T09:23:42","modified_gmt":"2022-10-26T07:23:42","slug":"vysetrenie-expresie-mmr-proteinov-v-nadoroch-endometria-imunohistochemicky-je-vhodny-sposob-primarnej-selekcie-potencialnych-pripadov-s-lynchovym-syndromom","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/vysetrenie-expresie-mmr-proteinov-v-nadoroch-endometria-imunohistochemicky-je-vhodny-sposob-primarnej-selekcie-potencialnych-pripadov-s-lynchovym-syndromom\/","title":{"rendered":"Using immunohistochemistry to examine MMR protein expression in endometrial tumours is a suitable method for the primary selection of potential cases with Lynch syndrome"},"content":{"rendered":"<p><span style=\"color: #ff0000;\"><strong>*A rare case of autochthonous human dirofilariasis with the manifestation of pseudotumor of the epididymis caused by helminth Dirofilaria repens<\/strong><\/span><\/p>\n<p><strong>\u00davod<\/strong><\/p>\n<p>Lynchov syndr\u00f3m, heredit\u00e1rne ochorenie s autozom\u00e1lne dominantn\u00fdm typom dedi\u010dnosti, vznik\u00e1 ako d\u00f4sledok z\u00e1rodo\u010dnej mut\u00e1cie v DNA mismatch repair gen\u00f3ch (MMR)(1). LS sa sp\u00e1ja s 30 \u2013 75 % rizikom vzniku karcin\u00f3mu hrub\u00e9ho \u010dreva u mu\u017eov, u \u017eeny je pravdepodobnos\u0165 vzniku kolorekt\u00e1lneho karcin\u00f3mu 25 \u2013 50 %(1). Poruchy z\u00e1rodo\u010dnej l\u00ednie v MMR DNA boli zisten\u00e9 u 1,8 % a\u017e 2,1 % pacientok s neselektovan\u00fdm karcin\u00f3mom endometria a a\u017e 9 % pacientok s karcin\u00f3mom endometria mlad\u0161\u00edch ako 50 rokov(2). \u010eal\u0161ie mal\u00edgne tumory asociovan\u00e9 s HNPCC s extrakolonickou lokalitou maj\u00fa pravdepodobnos\u0165 vzniku menej ako 15 %(3). LS sp\u00f4sob\u00ed ro\u010dne pribli\u017ene 4 000 kolorekt\u00e1lnych karcin\u00f3mov a 1 800 karcin\u00f3mov endometria (Centers for Disease Control and Prevention).<\/p>\n<p>&nbsp;<\/p>\n<h2>Karcin\u00f3m endometria ako s\u00fa\u010das\u0165 Lynchovho<\/h2>\n<p><strong>syndr\u00f3mu<\/strong><\/p>\n<p>Karcin\u00f3m endometria je naj\u010dastej\u0161\u00edm mal\u00edgnym n\u00e1dorom u \u017eien v z\u00e1padn\u00fdch \u010dastiach sveta. Celosvetovo narast\u00e1 incidencia karcin\u00f3mu endometria, najvy\u0161\u0161\u00ed v\u00fdskyt je v Severnej Amerike a z\u00e1padnej Eur\u00f3pe(4). Karcin\u00f3m endometria sa vyskytuje u star\u0161\u00edch \u017eien, priemerne okolo 70. roku \u017eivota, u \u017eien mlad\u0161\u00edch ako 40 rokov je tento karcin\u00f3m zriedkav\u00fd. V\u00fdskyt premal\u00edgnych a mal\u00edgnych por\u00fach endometria sa zvy\u0161uje v postmenopauz\u00e1lnom obdob\u00ed. Morfologicky ide o r\u00f4znorod\u00fa skupinu n\u00e1dorov s odli\u0161nou patogen\u00e9zou, spr\u00e1van\u00edm a progn\u00f3zou. Na z\u00e1klade klinickopatologick\u00fdch rysov boli tieto tumory trieden\u00e9 do dvoch skup\u00edn ako I. typ a II. typ. Typick\u00fdm morfologick\u00fdm predstavite\u013eom I. typu karcin\u00f3mov endometria je endometrioidn\u00fd karcin\u00f3m, ser\u00f3zny karcin\u00f3m pri II. type.<\/p>\n<p>Pacientky, ktor\u00e9 maj\u00fa endometri\u00e1lny karcin\u00f3m ako s\u00fa\u010das\u0165 LS, s\u00fa mlad\u0161ie \u2013 medi\u00e1n predstavuje 48. rok \u017eivota(5). Karcin\u00f3m endometria b\u00fdva asociovan\u00fd s I. typom(6), av\u0161ak relat\u00edvna frekvencia nonendometrioidn\u00fdch subtypov, ako je ser\u00f3zny a svetlobunkov\u00fd karcin\u00f3m, maj\u00fa vy\u0161\u0161\u00ed v\u00fdskyt pr\u00e1ve u pacientok s LS(5). U \u017eien s LS je po\u010diato\u010dn\u00e1 diagn\u00f3za karcin\u00f3mu endometria minim\u00e1lne tak\u00e1 pravdepodobn\u00e1, ako je riziko vzniku kolorekt\u00e1lneho karcin\u00f3mu. Uv\u00e1dza sa, \u017ee a\u017e u 26 % \u017eien, ktor\u00e9 pre\u017eili kolorekt\u00e1lny karcin\u00f3m ako s\u00fa\u010das\u0165 LS, sa rozvinie karcin\u00f3m endometria do 10 rokov od po\u010diato\u010dnej diagn\u00f3zy(7). Pacientky s mut\u00e1ciou MSH6 alebo MSH2 maj\u00fa vy\u0161\u0161ie riziko vzniku karcin\u00f3mu endometria s celo\u017eivotn\u00fdm rizikom a\u017e 44 %(7).<\/p>\n<p>&nbsp;<\/p>\n<h2>Genetick\u00e9 zmeny pri Lynchovom syndr\u00f3me<\/h2>\n<p>Genetick\u00fdm podkladom pre vznik Lynchovho syndr\u00f3mu je mut\u00e1cia niektor\u00e9ho z MMR prote\u00ednov. Medzi g\u00e9ny, k\u00f3duj\u00face tieto prote\u00edny patr\u00ed MSH2, MSH6, MLH1 a PMS2(8) alebo z\u00e1rodo\u010dn\u00e1 del\u00e9cia 3\u00b4 konca EPCAM (Epithelial Cell Adhesion Molecule), ktorej d\u00f4sledkom je epigenetick\u00fd silencing MSH2 g\u00e9nu(9). \u0160tyri z prote\u00ednov MMR tvoria dva funk\u010dn\u00e9 k\u013e\u00fa\u010de heterodim\u00e9ry pozost\u00e1vaj\u00face z MSH2\/MSH6 a MLH1\/PMS2. Mut\u00e1cia MSH2 a MSH6 sa nach\u00e1dza na chromoz\u00f3me 2p16, MLH1 na chromoz\u00f3me 3p21, PMS2 na chromoz\u00f3me 7p22(8). Po\u010das replik\u00e1cie DNA vznikaj\u00fa chyby, ktor\u00e9 s\u00fa za norm\u00e1lnych okolnost\u00ed n\u00e1sledne enz\u00fdmom DNA polymer\u00e1zou opravovan\u00e9. Prote\u00ednov\u00e9 produkty spom\u00ednan\u00fdch g\u00e9nov s\u00fa s\u00fa\u010das\u0165ou autorepara\u010dn\u00fdch mechanizmov v bunke. Tieto g\u00e9ny udr\u017euj\u00fa stabilitu gen\u00f3mu najm\u00e4 korekciou nespr\u00e1vne sp\u00e1rovan\u00fdch b\u00e1z, ktor\u00e9 sa generuj\u00fa po\u010das replik\u00e1cie DNA. Za fyziologick\u00fdch okolnost\u00ed vznikaj\u00fa z MMR g\u00e9nov multiprote\u00ednov\u00e9 komplexy, ktor\u00e9 maj\u00fa schopnos\u0165 rozl\u00ed\u0161i\u0165 a opravi\u0165 replika\u010dn\u00e9 chyby \u2013 tzv. mismatch, ktor\u00e9 vznikli pri naru\u0161enej synt\u00e9ze nov\u00e9ho vl\u00e1kna DNA. Poruchy MMR g\u00e9nov m\u00f4\u017eeme pozorova\u0165 pr\u00e1ve v mikrosatelitn\u00fdch repetit\u00edvnych sekvenci\u00e1ch DNA. Mikrosatelity s\u00fa kr\u00e1tke repetit\u00edvne sekvencie mo- no-, di-, tri- a tetranukleotidov vo\u013ene distribuovan\u00e9 v \u013eudskom gen\u00f3me a pr\u00e1ve poruchy v g\u00e9noch \u201emismatch\u201c repara\u010dn\u00e9ho syst\u00e9mu ved\u00fa k zmen\u00e1m v po\u010dte opakovan\u00ed t\u00fdchto sekvenci\u00ed. V\u00fdsledkom chybnej opravy je zmena v po\u010dte opakovan\u00ed mikrosatelitov, ke\u010f hovor\u00edme o mikrosatelitnej nestabilite (MSI)(10). MSI je \u010dasto sprievodn\u00fdm javom tumorov asociovan\u00fdch s LS.<\/p>\n<p>Ak s\u00fa zmutovan\u00e9 dve alebo viac z piatich mikrosatelitn\u00fdch sekvenci\u00ed v n\u00e1dorovej DNA, dan\u00fd tumor sa ozna\u010duje ako MSI-high (MSI-H). Ak bola zmutovan\u00e1 iba jedna z piatich mikrosatelitn\u00fdch sekvenci\u00ed v n\u00e1dorovej DNA, tak sa tumor ozna\u010duje ako MSI low (MSI-L). Ak nie je zmutovan\u00e1 \u017eiadna z piatich mikrosatelitn\u00fdch sekvenci\u00ed v n\u00e1dorovej DNA, dan\u00fd tumor sa naz\u00fdva mikrosatelitno stabiln\u00fd (MSS)(11). Pacienti s LS s\u00fa zvy\u010dajne nosite\u013emi z\u00e1rodo\u010dnej mut\u00e1cie v jednej alele g\u00e9nu MMR, druh\u00e1 alela je n\u00e1sledne inaktivovan\u00e1 mut\u00e1ciou, stratou heterozygozity alebo epigenetick\u00fdm silencingom.<\/p>\n<p>&nbsp;<\/p>\n<h2>Diagnostika Lynchovho syndr\u00f3mu<\/h2>\n<p>Pre jednoduch\u0161iu diagnostiku LS boli sformulovan\u00e9 Amsterdamsk\u00e9 krit\u00e9ri\u00e1, ktor\u00e9 v\u0161ak nezah\u0155\u0148ali v\u0161etky potrebn\u00e9 aspekty vzh\u013eadom na dok\u00e1zan\u00fa extrakolonick\u00fa propag\u00e1ciu LS, \u010do viedlo k \u00faprave v roku 1998(12). Nesk\u00f4r boli vypracovan\u00e9 Bethesda krit\u00e9ri\u00e1 zoh\u013ead\u0148uj\u00face stav mikrosatelitnej instability v danom n\u00e1dorovom tkanive(8). Diagn\u00f3za LS je stanoven\u00e1 na z\u00e1klade identifik\u00e1cie z\u00e1rodo\u010dn\u00e9ho heterozygotn\u00e9ho patog\u00e9nneho variantu v MSH2, MLH1, MSH6, PMS2 alebo del\u00e9cie EPCAM pri molekul\u00e1rnom genetickom testovan\u00ed(13).<\/p>\n<p>Testovanie mikrosatelitnej instability je senzit\u00edvna vy\u0161etrovacia met\u00f3da, ktor\u00e1 je schopn\u00e1 s vysokou pravdepodobnos\u0165ou odhali\u0165 poruchu mismatch repair syst\u00e9mu. Mikrosatelitn\u00e1 instabilita sa deteguje prostredn\u00edctvom polymer\u00e1zovej re\u0165azovej reakcie (PCR), kde sa vy\u0161etr\u00ed DNA z buniek zdrav\u00e9ho tkaniva a n\u00e1dorov\u00e9ho tkaniva pacienta, u ktor\u00e9ho je suspektn\u00fd LS. Pacienti, u ktor\u00fdch bola v n\u00e1dore zisten\u00e1 mikrosatelitn\u00e1 instabilita v najmenej dvoch mikrosatelitn\u00fdch sekvenci\u00e1ch, s\u00fa klasifikovan\u00ed ako MSI-H a s\u00fa pova\u017eovan\u00ed za vysokorizikov\u00e9 osoby pre rozvoj Lynchovho syndr\u00f3mu(14). Treba spomen\u00fa\u0165, \u017ee mikrosatelitn\u00e1 instabilita (MSI) je hypermutovate\u013en\u00fd fenotyp, ktor\u00fd obvykle vznik\u00e1 bu\u010f z\u00e1rodo\u010dnou mut\u00e1ciou v zlo\u017ek\u00e1ch MMR u pacientov s LS, alebo ako somatick\u00e1 hypermetyl\u00e1cia prom\u00f3tora MLH1 pri sporadick\u00fdch karcin\u00f3moch(15).<\/p>\n<p>&nbsp;<\/p>\n<h2>Imunohistoch\u00e9mia v prim\u00e1rnej selekcii potenci\u00e1lnych pr\u00edpadov s Lynchov\u00fdm syndr\u00f3mom<\/h2>\n<p>Testovanie MSI a imunohistoch\u00e9mia (IHC) s\u00fa komplement\u00e1rne vy\u0161etrenia. Strata expresie MMR prote\u00ednu IHC sa preuk\u00e1zala ako vysoko zhodn\u00e1 s testovan\u00edm mikrosatelitnej instability na b\u00e1ze DNA, pri\u010dom senzitivita je viac ako 90 % a \u0161pecificita je 100 %(14). Naj\u010dastej\u0161ie sa vy\u0161etruje strata expresie MLH1, MSH6, MSH2 a PMS2 mismatch repair prote\u00ednov. Pod\u013ea imunohistochemick\u00e9ho hodnotenia sa pri nepr\u00edtomnej expresii MLH1 a PMS2 ned\u00e1 spo\u013eahlivo ur\u010di\u0165 diagn\u00f3za LS. Pri absencii MSH2 a MSH6 prote\u00ednov alebo len absencii MSH6, pr\u00edpadne PMS2 prote\u00ednu je ve\u013emi pravdepodobn\u00e9, \u017ee pacient m\u00e1 Lynchov syndr\u00f3m. Ak s\u00fa, naopak, pr\u00edtomn\u00e9 prote\u00edny v\u0161etk\u00fdch 4 g\u00e9nov, t. j. MLH1, PMS2, MSH6 a MSH2, diagn\u00f3za LS je vyl\u00fa\u010den\u00e1. N\u00e1dory vykazuj\u00face stratu expresie MLH1 a PMS2 by mali by\u0165 \u010falej sk\u00faman\u00e9 na muta\u010dn\u00fd stav g\u00e9nu BRAF a zmeny prom\u00f3tora g\u00e9nu MLH1 na vyl\u00fa\u010denie sporadick\u00fdch pr\u00edpadov. Ak je v n\u00e1dore dok\u00e1zan\u00e1 MSI a z\u00e1rove\u0148 pr\u00edtomnos\u0165 mut\u00e1cie v g\u00e9ne BRAF alebo metyl\u00e1cie prom\u00f3tora MLH1, ide s vysokou pravdepodobnos\u0165ou o sporadick\u00fd typ karcin\u00f3mu(11).<\/p>\n<p>Pri podozren\u00ed na Lynchov syndr\u00f3m a dostupnosti n\u00e1dorov\u00e9ho tkaniva sa diagnostika za\u010d\u00edna imunohistochemick\u00fdm vy\u0161etren\u00edm MLH1, MSH6, MSH2 a PMS2 prote\u00ednov v n\u00e1dorovom tkanive a s\u00fa\u010dasne sa vykon\u00e1va anal\u00fdza mikrosatelitnej instability z DNA, ktor\u00e1 bola izolovan\u00e1 z n\u00e1dorov\u00e9ho tkaniva pacienta.<\/p>\n<p>Napriek zn\u00e1mej asoci\u00e1cii n\u00e1dorov endometria s LS nie s\u00fa v\u0161etky pr\u00edpady n\u00e1dorov endometria doposia\u013e \u0161tandardne geneticky testovan\u00e9. Diagnostika LS je ekonomicky a \u010dasovo n\u00e1ro\u010dn\u00e1, preto sa h\u013eadaj\u00fa postupy na jej zjednodu\u0161enie. Sekvenovanie z\u00e1rodo\u010dn\u00fdch mut\u00e1ci\u00ed sa pova\u017euje za zlat\u00fd \u0161tandard v diagnostike LS, v s\u00fa\u010dasnosti v\u0161ak st\u00e1le t\u00e1to met\u00f3da nie je v\u0161eobecne dostupn\u00e1 tak, aby mohla by\u0165 vyu\u017eit\u00e1 ako prim\u00e1rny skr\u00edningov\u00fd n\u00e1stroj(16). V kontraste s t\u00fdm je imunohistochemick\u00e9 testovanie jednoduch\u00e9, univerz\u00e1lne a lacn\u00e9, s 83 % senzitivitou a 89 % \u0161pecificitou, a to bez oh\u013eadu na to, o ktor\u00fd g\u00e9n MMR ide(16).<\/p>\n<p>&nbsp;<\/p>\n<h2>Metodika<\/h2>\n<p>S cie\u013eom overi\u0165 v\u00fdskyt straty expresie MMR prote\u00ednov sme hodnotili n\u00e1hodne vybran\u00fd bioptick\u00fd materi\u00e1l z rokov 2016 \u2013 2019 z oddelenia patol\u00f3gie Fakultnej nemocnice Nitra. Bioptick\u00fd materi\u00e1l pozost\u00e1val z tkan\u00edv z\u00edskan\u00fdch kyret\u00e1\u017eou pre neprimeran\u00e9 krv\u00e1canie s n\u00e1lezom endometrioidnej intraepitelovej neopl\u00e1zie (EIN) alebo hysterekt\u00f3miou pre n\u00e1dorov\u00e9 ochorenie maternice. Sk\u00faman\u00e9 vzorky poch\u00e1dzali od 46 pacientok, ktor\u00fdm bol diagnostikovan\u00fd karcin\u00f3m maternice v r\u00f4znom \u0161t\u00e1diu v\u00fdvoja. Pr\u00edpady zah\u0155\u0148ali:<\/p>\n<ul>\n<li>14 pacientok s EIN<\/li>\n<li>8 pacientok s EIN s prechodom do adenokarcin\u00f3mu<\/li>\n<li>15 pacientok s diagnostikovan\u00fdm endometrioidn\u00fdm adenokarcin\u00f3mom G1<\/li>\n<li>9 pacientok s diagnostikovan\u00fdm endometrioidn\u00fdm adenokarcin\u00f3mom G2<\/li>\n<\/ul>\n<p>V\u0161etky hodnoten\u00e9 tkaniv\u00e1 boli v \u00favodnej f\u00e1ze spracovan\u00e9 \u0161tandardn\u00fdm postupom, n\u00e1sledne fixovan\u00e9 4 % formaldehydom po\u010das 24 hod\u00edn, zaliate do paraf\u00ednu a narezan\u00e9 na 5 \u03bcm hrub\u00e9 rezy. N\u00e1sledne sme materi\u00e1l pripravili na imunohistochemick\u00fa anal\u00fdzu. Imunohistochemick\u00e9 farbenie na hodnoten\u00fd marker MSH6, MSH2, MLH1 a PMS2 prebiehalo v aparat\u00fare Imuno Autostainer (DAKO, Carpinteria, USA) pod\u013ea nasledovn\u00e9ho protokolu: tkaniv\u00e1 boli prepl\u00e1chnut\u00e9 pufrom dodan\u00fdm v\u00fdrobcom aparat\u00fary, revitalizovan\u00e9 v z\u00e1saditom pufri po\u010das 20 min\u00fat, prim\u00e1rna protil\u00e1tka (MSH6, MSH2, MLH1 a PMS2 monoklon\u00e1lna protil\u00e1tka) bola inkubovan\u00e1 60 min\u00fat, po prepl\u00e1chnut\u00ed pufrom boli prepar\u00e1ty inkubovan\u00e9 sekund\u00e1rnou protil\u00e1tkou (Histofine anti-mouse, anti-rabbit) po\u010das 30 min\u00fat. Po op\u00e4tovnom prepl\u00e1chnut\u00ed pufrom pou\u017eijeme na vizualiz\u00e1ciu syst\u00e9m diaminobenzid\u00ednu (DAKO, Carpinteria, USA) a nakoniec boli tkaniv\u00e1 dofarben\u00e9 hematoxyl\u00ednom. Imunohistochemicky pozit\u00edvne farbenie je definovan\u00e9 ako jednozna\u010dn\u00e1 nukle\u00e1rna expresia v n\u00e1dorov\u00fdch bunk\u00e1ch (<strong>ob-<\/strong><strong>r\u00e1zok<\/strong> <strong>1<\/strong>).<\/p>\n<p>&nbsp;<\/p>\n<h2>V\u00fdsledky<\/h2>\n<p>Na z\u00e1klade uveden\u00fdch diagnostick\u00fdch krit\u00e9ri\u00ed a imunohistochemickej anal\u00fdzy bola strata expresie niektor\u00e9ho MMR prote\u00ednu pr\u00edtomn\u00e1 u 23,91 % zo sk\u00faman\u00e9ho s\u00faboru pacientok (<strong>graf<\/strong><strong> 1<\/strong>). Dominovala najm\u00e4 strata expresie MLH1 (v 17 % pr\u00edpadov), expresia MSH2 a PMS2 nebola pr\u00edtomn\u00e1 v 13 % pr\u00edpadov. A\u017e na jednu vzorku v\u0161etky pr\u00edpady exprimovali MSH6 prote\u00edn (<strong>graf 1<\/strong>). Viacn\u00e1sobn\u00e1 strata expresie bola zachyten\u00e1 u 8 pacientok, \u010do tvor\u00ed 17,39 % pacientok. Strata expresie MMR prote\u00ednu nekorelovala s typom diagn\u00f3zy.<\/p>\n<p>&nbsp;<\/p>\n<h2>Diskusia<\/h2>\n<p>V na\u0161ej anal\u00fdze expresie MMR prote\u00ednov imunohistochemicky sa v 24 % pr\u00edpadov vyskytovala strata jedn\u00e9ho alebo viacer\u00fdch MMR prote\u00ednov. Strata expresie prote\u00ednu je definovan\u00e1 ako \u00fapln\u00e1 absencia jadrov\u00e9ho zafarbenia v n\u00e1dorov\u00fdch bunk\u00e1ch. V pr\u00edpade absencie expresie PMS2 a MLH1 prote\u00ednov test nevie s presnos\u0165ou ur\u010di\u0165, resp. vyl\u00fa\u010di\u0165 diagn\u00f3zy LS a je potrebn\u00e9 vykona\u0165 genetick\u00fa anal\u00fdzu. Preva\u017en\u00e1 v\u00e4\u010d\u0161ina diagn\u00f3z LS je d\u00f4sledkom mut\u00e1cie MLH1 alebo MSH2, preto\u017ee oba tieto g\u00e9ny s\u00fa esenci\u00e1lne pre tvorbu heteroduplexn\u00fdch dim\u00e9rov. Ak bola v\u00fdsledkom imunohistoch\u00e9mie strata expresie len u jedn\u00e9ho markera, v\u017edy je potrebn\u00e9 vy\u0161etri\u0165 aj metyla\u010dn\u00fd status na vyl\u00fa\u010denie diagn\u00f3zy LS.<\/p>\n<p>Imunohistoch\u00e9mia je relat\u00edvne lacn\u00e1, jednoduch\u00e1 met\u00f3da a m\u00e1 lep\u0161iu dostupnos\u0165 a r\u00fdchlej\u0161\u00ed \u010das spracovania v porovnan\u00ed s genetickou anal\u00fdzou. Ak by bola t\u00e1to met\u00f3da vyu\u017e\u00edvan\u00e1 ako rutinn\u00e9 vy\u0161etrenie tkaniva maternice, tak by sa mohol zv\u00fd\u0161i\u0165 z\u00e1chyt pacientok, ktor\u00e9 maj\u00fa mut\u00e1ciu MMR g\u00e9nov, e\u0161te pred rozvojom mal\u00edgneho ochorenia. Pacientky s LS maj\u00fa podobn\u00fa pravdepodobnos\u0165 rozvoja prvej malignity v endometriu aj v hrubom \u010dreve. Bolo by zauj\u00edmav\u00fdm zisten\u00edm, \u010di sa u niektor\u00fdch z na\u0161ich sledovan\u00fdch pacientok rozvinul aj kolorekt\u00e1lny karcin\u00f3m.<\/p>\n<p>Skor\u00e1 identifik\u00e1cia pacientov s LS je rozhoduj\u00faca pre klinick\u00fd mana\u017ement a progn\u00f3zu vr\u00e1tane skr\u00edningu najbli\u017e\u0161\u00edch \u010dlenov rodiny. Viacer\u00e9 \u0161t\u00fadie preuk\u00e1zali, \u017ee imunoterapia m\u00f4\u017ee ma\u0165 pr\u00ednos v lie\u010dbe pacientov s MMR mut\u00e1ciami bez oh\u013eadu na z\u00e1kladn\u00fa z\u00e1rodo\u010dn\u00fa mut\u00e1ciu.<\/p>\n<p>Ak by sa rutinn\u00e9 testovanie na pr\u00edtomnos\u0165 LS ka\u017ed\u00e9ho bioptick\u00e9ho tkaniva z maternice stalo zlat\u00fdm \u0161tandardom tak, ako je to pri kolorekt\u00e1lnom karcin\u00f3me, prispelo by to ku skor\u0161iemu zachyteniu pacientok s LS. Z\u00e1rove\u0148 by bolo pr\u00ednosn\u00e9 presn\u00e9 zis\u0165ovanie a identifik\u00e1cia genetick\u00fdch mut\u00e1ci\u00ed na lep\u0161ie porozumenie celkovej problematiky Lynchovho syndr\u00f3mu.<\/p>\n<p><strong><em>Po\u010fakovanie<\/em><\/strong><\/p>\n<p><em>\u201eT\u00e1to<\/em> <em>publik\u00e1cia<\/em> <em>vznikla<\/em> <em>v\u010faka<\/em> <em>podpore<\/em> <em>v<\/em> <em>r\u00e1mci<\/em> <em>Opera\u010dn\u00e9<\/em><em>ho programu Integrovan\u00e1 infra\u0161trukt\u00fara pre projekt: Cent<\/em><em>rum<\/em> <em>pre<\/em> <em>biomedic\u00ednsky<\/em> <em>v\u00fdskum<\/em> <em>\u2013<\/em> <em>BIOMEDIRES<\/em> <em>\u2013<\/em> <em>II.<\/em> <em>etapa, <\/em><em>k\u00f3d ITMS: 313011W428 a Dlhodob\u00fd strategick\u00fd v\u00fdskum a v\u00fdvoj zameran\u00fd na v\u00fdskyt Lynchovho syndr\u00f3mu v popul\u00e1cii SR a mo\u017enosti prevencie n\u00e1dorov spojen\u00fdch s t\u00fdmto syndr\u00f3mom spolufinancovan\u00fd zo zdrojov, k\u00f3d ITMS: 313011V578 spolufinancovan\u00fdch z Eur\u00f3pskeho fondu region\u00e1lneho rozvoja.\u201c<\/em><\/p>\n<p>&nbsp;<\/p>\n<p><strong>LITERAT\u00daRA<\/strong><\/p>\n<ol>\n<li>Hunter, J.E., et al. Universal screening for Lynch syndrome among patients with colorectal cancer: patient perspectives on screening and sharing results with at-risk Familial Cancer, 2017. 16(3): p. 377-387.<\/li>\n<li>Mills, A.M., et al. Lynch Syndrome Screening Should Be Considered for All Patients With Newly Diagnosed Endometrial American Journal of Surgical Pathology, 2014. 38(11): p. 1501-1509.<\/li>\n<li><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Van%20Lier%20MG%5BAuthor%5D\">Lier<\/a>, GF Van, <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Wagner%20A%5BAuthor%5D\">Wagner<\/a>, A., <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Van%20Leerdam%20ME%5BAuthor%5D\">Leerdam,<\/a> M.E. Van, et al. A review on the molecular diagnostics of Lynch syndrome: a central role for the pathology laboratory. Journal of cellular and molecular medicine, 2010. 14(1-2): p. 181-197.<\/li>\n<li>Yoon, G., et al. Stromal p16 expression is significantly increased in endometrial Oncotarget, 2017. 8(3): p. 4826-4836.<\/li>\n<li>Hanley, Z., G.G. Birdsong, and M.B. Mosunjac, Recent Developments in Surgical Pathology of the Uterine Corpus. Arch Pathol Lab Med, 2017. 141(4): p. 528-541.<\/li>\n<li>Niskakoski, et al. Converging endometrial and ovarian tumorigenesis in Lynch syndrome: Shared origin of synchronous carcinomas. Gynecologic Oncology, 2018. 150(1): p. 92-98.<\/li>\n<li>Cohen, A. and A. Leininger, The genetic basis of Lynch syndrome and its implications for clinical practice and risk management. Appl Clin Genet, 2014. 7: p. 147-58.<\/li>\n<li>Duraturo, et al. Genetics, diagnosis and treatment of Lynch syndrome: Old lessons and current challenges. Oncol Lett, 2019. 17(3): p. 3048-3054.<\/li>\n<li>Pai, R.K., et al., DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch Modern Pathology, 2018. 31(10): p. 1608-1618.<\/li>\n<li>Sehgal, et al. Lynch syndrome: an updated review. Genes (Basel), 2014. 5(3): p. 497-507.<\/li>\n<li>Umar, A., et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst, 96(4): p. 261-8.<\/li>\n<li>Vasen, F.A., et al. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch Syndrome) proposed by the International Collaborative Group n HNPCC. Gastroenterology, 1999. 116(6): p. 1453- 1456.<\/li>\n<li>Idos, and L. Valle, Lynch Syndrome, in GeneReviews((R)), M.P. Adam, et al. Editors. 1993: Seattle (WA).<\/li>\n<li>Kawakami, MSI testing and its role in the management of colorectal cancer. Current Treatment Options in Oncology 2015. 16(7): p. 30.<\/li>\n<li>Remo, M. Fassan, and G. Lanza, Immunohistochemical evaluation of mismatch repair proteins in colorectal carcinoma: the AIFEG\/GIPAD proposal. Pathologica, 2016. 108(3): p. 104-109.<\/li>\n<li>Wang, et al. The practice of universal screening for Lynch syndrome in newly diagnosed endometrial carcinoma. Health Sci Rep, 2018. 1(7): p. e43.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>*A rare case of autochthonous human dirofilariasis with the manifestation of pseudotumor of the epididymis caused by helminth Dirofilaria repens \u00davod Lynchov syndr\u00f3m, heredit\u00e1rne ochorenie s autozom\u00e1lne dominantn\u00fdm typom dedi\u010dnosti, vznik\u00e1 ako d\u00f4sledok z\u00e1rodo\u010dnej mut\u00e1cie v DNA mismatch repair gen\u00f3ch (MMR)(1). LS sa sp\u00e1ja s 30 \u2013 75 % rizikom vzniku karcin\u00f3mu hrub\u00e9ho \u010dreva u<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[297],"tags":[1877,763,1068],"class_list":["post-2450","post","type-post","status-publish","format-standard","hentry","category-pathology","tag-endometrium-en","tag-immunohistochemistry","tag-lynch-syndrome","typ_clanku-original-work"],"acf":{"abstrakt":"<p>Lynch syndrome (LS), or hereditary non-polyposis colorectal cancer (HNPCC), is an autosomal dominant disease in which mutations occur in genes for MMR proteins responsible for DNA repair during replication. Patients with Lynch syndrome are likely to develop colorectal cancer in both sexes, with an added risk of endometrial cancer in females. Diagnosis of Lynch syndrome is based on identifying a germline heterozygous pathogenic variant in MSH2, MLH1, MSH6, PMS2, or deletion of the EPCAM gene in molecular genetic testing. Immunohistochemical analysis of MMR proteins is a widely accepted routine screening method with relatively high sensitivity and specificity. In our series, we analyzed the expression of MMR proteins on endometrial cancer tissues. The analysis showed a loss of one or more MMR proteins was present in 24% of cases. Immunohistochemistry is a relatively inexpensive, simple and accessible method for the primary selection of potential cases with Lynch syndrome. If routine MMR protein expression testing of every biopsy tissue from the uterus were to become standard, as it is for colorectal cancer, it would contribute to earlier detection of patients with Lynch syndrome.<\/p>\n<p><strong>Keywords: <\/strong>Lynch syndrome, endometrium, immunohistochemistry<\/p>\n","casopis":[{"ID":2437,"post_author":"7","post_date":"2022-10-26 08:29:25","post_date_gmt":"2022-10-26 06:29:25","post_content":"<strong>newslab 1\/2022<\/strong>\r\n<ul>\r\n \t<li>Using immunohistochemistry to examine MMR protein expression in endometrial tumours is a suitable method for the primary selection of potential cases with Lynch syndrome<\/li>\r\n \t<li>Metabolomics: a\u00a0potential tool for an individual approach to depressive diseases<\/li>\r\n \t<li>The role of epigenetics in endometrial cancer<\/li>\r\n \t<li>Vaccine vulnerabilities: can we prevent them?\r\n\u2013 SARS-CoV-2 case study<\/li>\r\n<\/ul>","post_title":"newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-9","to_ping":"","pinged":"","post_modified":"2022-10-26 08:32:07","post_modified_gmt":"2022-10-26 06:32:07","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.newslab.sk\/casopis\/newslab-9\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"5-8","upload_clanok":{"ID":2443,"id":2443,"title":"NEWSLAB 1-2022_Miku\u0161-Kuracinov\u00e1 -patologia","filename":"NEWSLAB-1-2022_Mikus-Kuracinova-patologia.pdf","filesize":1107680,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2022\/10\/NEWSLAB-1-2022_Mikus-Kuracinova-patologia.pdf","link":"https:\/\/www.newslab.sk\/en\/vysetrenie-expresie-mmr-proteinov-v-nadoroch-endometria-imunohistochemicky-je-vhodny-sposob-primarnej-selekcie-potencialnych-pripadov-s-lynchovym-syndromom\/newslab-1-2022_mikus-kuracinova-patologia-2\/","alt":"","author":"7","description":"","caption":"","name":"newslab-1-2022_mikus-kuracinova-patologia-2","status":"inherit","uploaded_to":2450,"date":"2022-10-26 06:58:04","modified":"2022-10-26 06:58:04","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/2450","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=2450"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/2450\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=2450"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=2450"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=2450"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}