| Abstract | Ciljevi istraživanja: Glavni su ciljevi istraživanja bili su odrediti udio trostruko negativnih
karcinoma dojke s pozitivnim PD-L1 statusom, korelirati PD-L1 status s ostalim ispitivanim
kliničko-patološkim karakteristikama tumora te utvrditi postojanje promjene PD-L1 statusa u
različitim vrstama patohistoloških uzoraka.
Ispitanici i postupci: U istraživanje je uključeno 112 ispitanika, kojima je na Zavodu za
patologiju, sudsku medicinu i citologiju, KBC-a Split u razdoblju od 2019. do 2022. godine
određen PD-L1 status. Uvidom u patohistološke nalaze izdvojeni su podatci o PD-L1 statusu i
korelirani s ostalim dostupnim kliničko-patološkim podatcima (vrsta uzorka, dob, spol,
histološki tip tumora, histološki gradus, veličina tumora, lokalizacija, lateralizacija, vaskularna
invazija, zahvaćanje limfnih čvorova, Ki-67 proliferacijski indeks).
Rezultati: U istraživanoj skupini koja uključuje ukupno 112 ispitanika udio trostruko
negativnih karcinoma dojke sa pozitivnim PD-L1 statusom iznosio je 56%. U ispitivanoj
skupini bilo je značajno više ženskih ispitanika u odnosu na muške (P<0,001), sa srednjom
vrijednošću dobi od 65±13 godina. Srednja vrijednost Ki-67 proliferacijskog indeksa iznosila
je 50±24. Obzirom na vrstu uzorka na kojima je rađena analiza PD-L1 statusa statistički su
značajno predominirale iglene biopsije (49,2%) u odnosu na ostale vrste uzoraka (P<0,001).
Uspoređujući gradus tumora na kojima je rađena analiza PD-L1 statusa, bilo je statistički
značajno više karcinoma gradusa III (62,5%) (P<0,001). Nije pronađena statistički značajna
razlika u lateralizaciji, te je gotovo podjednak broj tumora bio dijagnosticiran u lijevoj (44,4%)
i desnoj dojci (50,6%) (P=496). Gledajući lokalizaciju tumora, bilo je statistički značajno više
uzoraka s tumorima smještenim u gornjem lateralnom kvadrantu (61,5%) u odnosu na ostale
kvadrante dojke (P<0,001). Zabilježeno je statistički značajno više tumora bez prisutne
vaskularne invazije (83,9%) (P<0,00) i bez infiltracije limfnih čvorova (75%) (P=0.009).
Promatrajući razliku ispitivanih varijabli u odnosu na PD-L1 status, nađena je značajna razlika
u odnosu na gradus tumora i Ki-67 proliferacijski indeks pri čemu je u grupi TNBC s pozitivnim
PD-L1 statusom bilo dvostruko više tumora histološkog gradusa III (P=0,001), a proliferacijski
indeks Ki-67 bio je 1,5 puta veći u odnosu na grupu TNBC s negativnim PD-L1 statusom
(P=0,009). Nije pronađena statistički značajna razlika u odnosu na dob bolesnica, veličinu
tumora, histološki tip tumora, vaskularnu invaziju kao ni zahvaćanje limfnih čvorova. Promjena
u PD-L1 statusu zabilježena je kod ukupno 6 bolesnica nakon što je testiranje ponovljeno na
dodatnim uzorcima.
Zaključak: Pozitivan PD-L1 ICS prisutan je u oko 40-50 % trostruko negativnih karcinoma
dojke, što nudi mogućnost primjene ciljane imunoterapije inhibitorima kontrolnih točaka u ovoj
skupini tumora sa vrlo ograničenim terapijskim opcijama. Budući da je imuni okoliš podložan
dinamičkim promjenama uz mogućnost promjene PD-L1 statusa, za pacijentice sa negativnim
PD-L1 statusom korisno je testiranje ponoviti i na drugim dostupnim uzorcima. |
| Abstract (english) | Objectives and background: The main objectives of the research were to determine the
proportion of triple-negative breast cancers with a positive PD-L1 status, to correlate the PDL1 status with other investigated clinico-pathological characteristics and to determine the
existence of changes in the PD-L1 status in different types of pathohistological samples.
Patients and methods: 112 patients were included in the research, for whome PD-L1 status
was determined at the Department of Pathology, Forensic Medicine and Cytology, Universitiy
Hospitalof Split in the period from January 2019 to December 2022. By examining the
pathohistological findings, data on PD-L1 status were extracted and correlated with other
available clinico-pathological data (specimen type, age, sex, histological type of tumor,
histological grade, tumor size, localization, lateralization, vascular invasion, involvement of
lymph nodes, Ki-67 proliferation index).
Results: In the research group, which included a total of 112 patients, the proportion of triplenegative breast cancers with a positive PD-L1 status was 56%. In the examined group, there
were significantly more female compared to male patients (P<0.001), with a mean age of 65±13
years. The mean value of the Ki-67 proliferation index was 50±24. Considering the type of
sample on which the analysis of PD-L1 status was performed, needle biopsies (49.2%)
predominated significantly compared to other types of samples (P<0.001). Comparing the
grades of tumors on which PD-L1 status analysis was performed, there were significantly more
grade III tumors (62.5%) (P<0.001). No statistically significant difference in lateralization was
found and an almost equal number of tumors were diagnosed in the left (44.4%) and right breast
(50.6%) (P=496). Looking at the tumor localization, there were significantly more samples with
tumors located in the upper lateral quadrant (61.5%) compared to other quadrants of the breast
(P<0.001). A statistically significant number of tumors without vascular invasion (83.9%)
(P<0.00) and without lymph node infiltration (75%) (P=0.009) were recorded. Observing the
difference of the examined variables in relation to PD-L1 status, a significant difference was
found in relation to tumor grade and Ki-67 proliferation index, whereby in the TNBC group
with positive PD-L1 status there were twice as many tumors of histological grade III (P=0.001
), and the Ki-67 proliferation index was 1.5 times higher compared to the TNBC group with
negative PD-L1 status (P=0.009). No statistically significant difference was found in relation to patient age, tumor size, tumor
histological type, vascular invasion, and lymph node involvement. A change in PD-L1 status
was recorded in 6 patients after the testing was repeated on additional samples..
Conclusion: Positive PD-L1 ICS is present in about 40-50% of triple-negative breast cancers,
which offers the possibility of using targeted immunotherapy with checkpoint inhibitors in this
group of tumors with very limited therapeutic options. Since the immune environment is
subjected to dynamic changes with the possibility of changing the PD-L1 status, it is beneficial
for patients with a negative PD-L1 status to repeat the testing on other available samples. |
