Izraženost i prognostičko značenje PD-L1 u HER2 pozitivnim karcinomima dojke

doctoral thesis

• Title (english): Expression and prognostic significance of PD-L1 in HER2 positive breast carcinomas
• Author: Melita Perić Balja
• Mentor: Davor Tomas (mentor)
• Committee member: Božo Krušlin (predsjednik povjerenstva)
• Committee member: Čedna Tomasović-Lončarić (član povjerenstva)
• Committee member: Lidija Beketić-Orešković (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2022-06-01, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Oncology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Clinical Cytology
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Do pojave ciljane anti-HER2 terapije, HER2 pozitivni karcinomi dojke (HER2+ KD) imali su najlošiju prognozu, a uvođenjem neoadjuvantne anti-HER2 terapije (NAT) dodatno je poboljšano preživljenje bolesnica. Unatoč uspjesima NAT, dio bolesnica pokazuje rezistenciju na ciljanu terapiju i za njih se traže drugi terapijski modaliteti.
Cilj našeg istraživanja je odrediti imunohistokemijsku izraženost PD-L1 na limfocitima infiltriranim u područje tumora (TIL) i tumorskim stanicama 122 bolesnice s HER2+ KD (62 luminalni podtip i 60 čisti HER2 podtip) koje nisu imale kompletan patološki odgovor na NAT. Naši rezultati pokazuju da HER2+ KD čistog HER2+ imunofenotipa imaju bolji odgovor na NAT od LumHER2+ (P=0,019). Pozitivan PD-L1 u TILovima zabilježen je u 40,2% svih uzoraka dok je u 7,4% slučajeva PD-L1 pozitivan u stanicama karcinoma. Čisti HER2+ podtip češće ima pozitivan PD-L1 u TIL (P=0,096) i u stanicama karcinoma (P=0,024) nego LumHER2+. Pozitivan PD-L1 u TIL ne korelira s kliničkopatološkim karaktersitikama KD, osim s višim Ki-67 u ostatnom tumoru (P=0,043). Izraženost PD-L1 u TIL nije u korelaciji s RCB niti s rizikom od povrata bolesti dok izraženost PD-L1 u karcinomu korelira s lošijom prognozom. LumHER2+ značajno rjeđe imaju progresiju bolesti od HER2+ podtipa (P=0,019). Najveći utjecaj na povrat bolesti ima pozitivni status limfnih čvorova (P=0,003), veći tumori pri dijagnozi (P=0,022) te lošiji odgovor na NAT (P=0,028). Naši rezultati upućuju da bi dio bolesnica koje nisu imale potpun odgovor na NAT bile kandidati za terapiju blokatorima PD-L1, posebice one s čistim HER2+ podtipom.

Abstract (english)

Prior to targeted therapy, HER2-positive breast cancers (HER2+ BC) had a poor prognosis, and further improvement in survival was achieved with the introduction of neoadjuvant anti-HER2 therapy (NAT). However, some patients still have resistance. Therefore, our goal was to determine the immunohistochemical expression of PD-L1 on tumor-infiltrated lymphocytes (TIL) of HER2+ BC who did not have a complete pathological response to NAT. Our results show that HER2+ BC of pure HER2+ immunophenotype (ER-negative) have a better response to NAT than LumHER2+ (P=0.019). PD-L1 in TILs was positive in 40.2% of all cases, and 7.4% of BC expressed PD-L1 in cancer cells. The expression of PD-L1 in TILs does not correlate with clinicopathological characteristics of BC, nor with the response to therapy or recurrence of the disease. PD-L1 positive cancer cells are more common in HER2+ than LumHER2+ (P = 0.024) and correlate with a poorer prognosis. LumHER2+ have better disease-free survival than HER2+ subtype (P=0,019). Positive status of lymph nodes (P=0.003), larger tumors at diagnosis (P=0.022) and poorer response to NAT (P=0.028) have the greatest impact on recurrence. We can conclude that therapy with anti-PD-L1 inhibitors could target PD-L1-positive BC without a complete response to NAT, especially those with pure HER2+ immunophenotype.

• Keywords: karcinomi dojke; anti-HER2 neoadjuvantna terapija; PD-L1 izraženost; DFS
• Keywords (english): breast cancer; anti-HER2 neoadjuvant chemotherapy; PD-L1 expression; DFS
• Language: croatian
• URN:NBN: urn:nbn:hr:105:228555
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 117 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-09-19 11:13:34