Title Imunohistokemijska analiza izraženosti antigena skupine rak-testis u neinvazivnim duktalnim karcinomima dojke Title (english) Immunohistochemical analysis of cancer/testis antigens in noninvasive ductal breast cancer Author Ana Roguljić Mentor Antonio Juretić (mentor)Mentor Božena Šarčević (komentor)Committee member nije dostupno (član povjerenstva) Granter University of Zagreb Defense date and country 2019-11-29, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 61 - Medical sciences Abstract Rak-testis antigeni su velika porodica tumorskih antigena, koji su izraženi u različitim vrstama tumora, a u normalnom tkivu nalaze se samo u stanicama testisa, spermatognijama i spermatocitima (engl. cancer/testis antigens; C/T) i na stanicama tkiva posteljice (trofoblasti). Brojna istraživanja koja su se bavila analizom izraženosti rak-testis antigena u invazivnom karcinomu dojke pokazala su da je njihova izraženost znatno veća u visokog histološkog gradusa. No izraženost rak-testis antigena u duktalnom neinvazivnom karcinomu dojke (DCIS) nedovoljno je istražena. U ovom retrospektivnom istraživanju analizirana je izraženost rak-testis antigena iz skupine MAGE-A (MAGE-A1, MAGE-A10 i multi-MAGE-A) i NY-ESO-1 kod 83 bolesnice s dijagnozom duktalnog neinvazivnog karcinoma dojke. Sve analizirane bolesnice liječene su na Institutu za tumore (KBCSM) u razdoblju od 2007. - 2014. godine. Kod svih bolesnica je učinjen poštedni kirurški zahvat (lumpektomija, segmentektomija) te je kod svih provedena radioterapija, a endokrinu terapiju su primale one bolesnice koje su imale pozitivne ER i/ili PR receptore. Pacijentice su praćene između 1 - 8 godina (srednja vrijednost 5.02. godine). Imunohistokemijskom metodom analizirana je izraženost rak-testis antigena u materijalu, a uz to i njihov odnos s prediktivnim i prognostičkim čimbenicima duktalnog neinvazivnog karcinoma dojke (izraženost estrogenskih i progesteronskih receptora, gradus jezgre, veličina tumora, središnja nekroza i udaljenost od kirurškoga ruba). Također je analizirana i prisutnost tumor-infiltrirajućih limfocita u materijalu (TIL). Statistička analiza podataka pokazala je postojanje statistički signifikantne veze između izraženosti promatranih rak-testis antigena te patohistoloških prediktivnih i prognostičkih čimbenika za DCIS. Dodatna analiza izraženosti TIL-ova pokazala je statistički signifikantnu pozitivnu korelaciju s gradusom, centralnom nekrozom te negativnu statistički signifikantnu korelaciju s izraženosti ER i PR receptora, što je u skladu s dosadašnjim istraživanjima. Analizirana je i povezanost načina izraženosti promatranih rak-testis antigena u duktalnom neinvazivnom karcinomu dojke (bojenje citoplazme, bojenje jezgre, simultano bojenje jezgre i citoplazme) s patohistološkim i prediktivnim čimbenicima duktalnog neinvazivnog karcinoma dojke te lokalnim recidivom. Iz dobivenih rezultata može se zaključiti da je istodobno bojenje jezgre i citoplazme neovisan prediktor lokalnog povrata bolesti S obzirom na dobivene rezultate može se zaključiti da rak-testis antigeni nisu savršeni pokazatelji invazivnosti duktalnog neinvazivnog karcinoma dojke,
ali u kombinaciji s drugim prediktivnim i prognostičkim čimbenicima mogu biti putokaz u odabiru načina liječenja bolesnica s tom dijagnozom.
Abstract (english) Cancer/testis antigens (CTAs) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues, with the exception of the testes and placenta. Numerous immunohistochemical studies have reported associations between CTA expression and a negative estrogen receptor (ER) status in breast tumors and demonstrated that CTAs are frequently expressed in tumors with higher nuclear grade. The expression of CTAs has not been studied as extensively in ductal carcinoma in situ (DCIS) as it has been in invasive breast cancer. The present retrospective study included archived paraffin-embedded specimens from 83 patients diagnosed with DCIS in the period between January 2007 and December 2014. The follow-up time for local recurrence ranged between 1 and 8 years (mean, 5.02 years). Antigens from the melanoma-associated antigen gene (MAGE) family, namely multi-MAGE-A, MAGE-A1, MAGE-A10 and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen, were evaluated by immunostaining and their subcellular location was investigated. Presence of tumor-infiltrating lymphocytes (TILs) was evaluated on all sections, together with the histopathological variables of DCIS. Specific tested antigens exhibited associations with histopathological parameters for DCIS and all demonstrated statistically significant associations with nuclear staining, simultaneous cytoplasmic and nuclear staining, and local recurrence. Additional analysis of TILs indicated that they were significantly associated with tumor grade (P=0.023), central necrosis (P<0.001), ER (r=-0.322, p=0.003) and PR (r=-0.285, p=0.009). Overall, CTAs from the MAGE family (MAGE-A1, multi-MAGE-A and MAGE-A10) and NY-ESO-1 associate with histopathological predictive variables of DCIS. The expression of antigens NY-ESO-1 and MAGE-A10 could serve an important role in the treatment of patients with negative histopathological predictive variables, but further analysis is required. Simultaneous cytoplasmic and nuclear protein expression of MAGE-A family and NY-ESO-1 CTAs may represent an independent marker for local recurrence. Taken together, the present data suggest that CTAs are not perfect indicators of invasiveness for DCIS but could inform treatment strategies for patients when taken in combination with other histopathological predictive variables. However, this was a small study and further larger studies will be necessary to confirm the current findings.
Keywords
medicina
Keywords (english)
medicine
Language croatian URN:NBN urn:nbn:hr:105:947191 Study programme Title: Biomedicine and Health Sciences Type of resource Text Extent 86 str. File origin Born digital Access conditions Open access Terms of use Repository Dr Med - University of Zagreb School of Medicine Digital Repository Created on 2023-05-05 08:46:11
