| Abstract | Cilj istraživanja: Gubitak ekspresije CDX2 proteina je od ranije povezan s dMMR kod
bolesnika s kolorektalnim karcinomom (CRC). Međutim, postoji vrlo malo studija koje su
istražile povezanost gubitka ekspresije CDX2 proteina s gubitkom ekspresije svakog od MMR
proteina zasebno. Cilj je ovog istraživanja istražiti povezanost gubitka ekspresije CDX2
proteina kod oboljelih od CRC s gubitkom ekspresije MLH1, MSH2, MSH6 i PMS2 proteina.
Materijali i metode: Ovo je retrospektivna studija koja je obuhvatila 327 bolesnika koji su
operirani zbog CRC-a. Devet bolesnika (2,9 %) imalo je sinkrone CRC-e pa je ukupni uzorak
bio 336 CRC-a. U bazu podataka prikupljeni su podaci o histološkom tipu tumora,
diferencijaciji tumora, perineuralnoj, limfnoj i vaskularnoj invaziji, T i N stadiju tumora te
broju intratumorskih limfocita i limfocita oko tumora. Nakon imunohistokemijske analize u
bazu podataka su uneseni i podaci o ekspresiji CDX2, MLH1, MSH2, MSH6 i PMS2 proteina.
Rezultati: Gubitak ekspresije CDX2 proteina nađen je kod 19 od 336 CRC (5,9 %) i statistički
je značajno povezan sa smještajem karcinoma na cekumu i uzlaznom kolonu, djelomično
mucinoznim karcinomima, slabo diferenciranim karcinomima i s dMMR. Nađena je statistički
značajna povezanost gubitka ekspresije CDX2 proteina s gubitkom ekspresije MLH1 i PMS2
proteina. Uzimajući u obzir da MMR geni funkcioniraju u paru, daljnja analiza je rađena s
MLH1/PMS2 i MSH2/MSH6 heterodimerom. Analiza je pokazala da je gubitak ekspresije
CDX2 proteina statistički značajno povezan sa gubitkom funkcije MLH1/PMS2 heterodimera.
Stvoren je regresijski model za gubitak ekspresije CDX2 proteina i dMMR. Prediktori gubitka
ekspresije CDX2 proteina su slabo diferencirani karcinomi i disfunkcija MLH1/MSH2
heterodimera. Smještaj CRC-a na cekumu i uzlaznom kolonu te gubitak ekspresije CDX2
proteina pozitivni su prediktori za dMMR dok je smještaj karcinoma na rektumu negativan
prediktor za dMMR.
Zaključak: Ova je studija pokazala značajnu povezanost gubitka ekspresije CDX2 proteina s
gubitkom ekspresije MLH1 i PMS2 proteina kod bolesnika sa CRC-om. Regresijski model
pokazao je da su slaba diferenciranost karcinoma i disfunkcija MLH1/PMS2 heterodimera
potencijali prediktori za gubitak ekspresije CDX2 proteina. Ovo je prva studija koja je uključila
gubitak ekspresije CDX2 proteina u regresijski model za dMMR i pokazala da se gubitak
ekspresije CDX2 proteina može koristiti kao potencijali prediktor za dMMR. |
| Abstract (english) | Objectives: CDX2 expression loss is commonly associated with mismatch repair deficiency
(dMMR) in colorectal cancer (CRC). However, there are only a few studies that have attempted
to correlate CDX2 expression loss with specific MMR proteins. The aim of this study is to
explore the association between CDX2 expression loss and MLH1, MSH2, MHS6, PMS2
expression loss in CRC patients.
Materials and methods: This is a retrospective study of 327 patients who underwent surgery
due to CRC. Nine patients (2.9%) had two synchronous CRCs, thus making the total sample
336 CRCs. Histopathological data such as tumor type, tumor grade, perineural, lymphatic, and
vascular invasion, pT stage, pN stage, peritumoral and intratumoral lymphocytic infiltration
were collected and recorded in the database. After immunohistochemical analysis, CDX2
expression, MLH1, MSH2, MSH6, and PMS2 deficiency were also recorded.
Results: CDX2 expression loss was detected in 19 out of 336 CRCs (5.9%) and was associated
with ascending colon CRC, partially mucinous adenocarcinoma, poorly differentiated
carcinoma, and dMMR. Forty-four (13.1%) of the CRCs were dMMR. There was a statistically
significant association between CDX2 expression loss and MLH1 and PMS2 deficiency.
Considering that most expression phenotypes include pairs of MMR genes, MLH1/PMS2 and
MSH2/MSH6 were analyzed as heterodimers. Analysis of heterodimers showed a similar
result, namely, that MLH1/PMS2 heterodimer deficiency was significantly associated with
CDX2 expression loss. A regression model was constructed for CDX2 expression loss and for
dMMR. Poor tumor differentiation and MLH1/PMS2 heterodimer deficiency have been
identified as potential predictors for CDX2 expression loss. CRC in the ascending colon and
CDX2 expression loss have been identified as positive potential predictors of dMMR with
rectal cancer as a negative potential predictor of dMMR.
Conclusion: This study showed a significant association between CDX2 expression loss and
MLH1 and PMS2 deficiency in CRC. A regression model for CDX2 expression showed that
poor tumor differentiation and MLH1/PMS2 heterodimer deficiency are independent factors
for CDX2 expression loss. This is the first study which included CDX2 expression in a
regression model for dMMR and showed that CDX2 expression loss can be used as a predictive
factor for dMMR. |
