| Abstract | Ciljevi: Osnovni ciljevi ovog istraživanja bili su utvrditi razinu izražaja HER2 receptora u
kolorektalnim karcinomima te utvrditi povezanost izražaja HER2 receptora sa kliničko-patološkim
karakteristikama tumora.
Materijali i metode: U istraživanje je uključeno 144 bolesnika s kolorektalnim karcinomom za
koje je u razdoblju od 1. siječnja 2019. godine do 31. prosinca 2022. godine na Kliničkom zavodu
za patologiju, sudsku medicinu i citologiju KBC-a Split imunohistokemijski određen HER2 status.
Uvidom u medicinsku dokumentaciju dobiveni su ostali kliničko-patološki podaci (dob, spol,
lokalizacija tumora, veličina tumora, histološki tip, histološki gradus, limfokapilarna invazija,
ekstamuralna vaskularna invazija, tumorsko pupanje, perineuralna invazija, postojanje tumorskih
depozita, status limfnih čvorova, klinički stadij bolesti). Za usporedbu ispitivanih varijabli korišten
je χ2-test.
Rezultati: Medijan životne dobi ispitanika iznosio je 67 godina (raspon 32-83 godine). Muškaraca
je statistički bilo značajno više u odnosu na žene (P=0,015). Sigmoidni kolon je bio statistički
značajno najčešća lokalizacija tumora (P<0,0001). Najviše tumora je bilo dijagnosticirano u IIIB
ili IIIC TNM stadiju bolesti što je bilo statistički značajno (P<0,0001). Postojala je statistički
značajna razlika u HER2 statusu (P<0,0001), većina tumora, njih 140 (97,2%) je bila HER2
negativna, a HER2 pozitivnih je bilo 4 (2,8%). U dva HER2 pozitivna bolesnika tumor je bio
lokaliziran u transverzalnom kolonu, dok je u preostala dva tumor bio lokaliziran u distalnom
kolonu. Svi su bili dijagnosticirani u IV. stadiju bolesti, a najčešće sijelo metastaza bila su pluća
(75%). Kod jednog bolesnika (25%) s HER2 pozitivnim kolorektalnim karcinomom su detektirane
mutacije KRAS gena, dok je kod preostalih bolesnika (75%) KRAS bio divlji tip. Svi bolesnici su
imali NRAS/BRAF divlji tip tumora i bili su mikrosatelitski stabilni.
Zaključci: Unatoč tome što je HER2 pozitivnost prisutna u <5% slučajeva, određivanje HER2
statusa preporučuje se za sve bolesnike s metastatskim kolorektalnim karcinomom, osobito kod
tumora s RAS/BRAF divljim tipom te u onih kojima je bolest progredirala uz raniju terapiju. Rana
identifikacija ovih bolesnika omogućuje odabir prikladnih terapijskih opcija i identifikaciju
bolesnika koji mogu imati koristi od anti-HER2 terapije. Trenutno je u tijeku veći broj kliničkih
studija s različitim HER2- ciljajućim lijekovima koje za sada pokazuju obećavajuće rezultate. |
| Abstract (english) | Objectives: The main aim of this study was to establish immunohistochemical expression of
HER2 in colorectal cancer and to identify relations with other clinicopathological characteristics.
Patients and methods: The study included 144 patients diagnosed with colorectal cancer for
whom HER2 status was immunohistochemically determined at the Clinical Department of
Pathology, Forensic Medicine and Cytology of the University Hospital of Split from January 1,
2019 to December 31, 2022. Other clinicopathological data (age, gender, tumor localization, tumor
size, histological type, histological grade, lymphovascular invasion, extramural vascular invasion,
tumor budding, perineural invasion, tumor deposits, lymph node status, clinical stage) were
obtained by reviewing the medical documentation. For comparison of the examined variables χ2-
test was used.
Results: The median age of the participants was 67 years (range 32-83 years). There was a
statistically significant higher propotrion of males compared to females (P=0.015). The most
common tumor localization was the sigmoid colon, which was statistically significant (P<0,0001).
The majority of patients were in TMM stage IIIB and IIIC, which was statistically significant.
There was a statistically significant difference in HER2 status (P<0.0001), with the majority of
tumors, 140 (97.2%) being HER2 negative, and 4 (2.8%) being HER2 positive. In two HER2
positive patients, the tumor was localized in the transverse colon, while in the remaining two, the
tumor was localized in the distal colon. All patients were diagnosed at stage IV of the disease, and
the lung was the most common metastatic site. In one patient (25%) with HER2 positive colorectal
cancer KRAS gene mutations were detected, while the remaining patients (75%) had wild-type
KRAS. All patients had wild-type NRAS/BRAF tumors and were microsatellite stable.
Conclusions: Despite HER2 positivity being present in less than 5% of cases, HER2 testing is
recommended for all patients with metastatic colorectal cancer, particulary those whose disease
has progressed on prior therapy and those who have tumors with RAS/BRAF wild-type. Early
identification of these patients enables the selection of appropriate therapeutic options and
identification of patients who may benefit from anti-HER-targeted therapy. Few trials on HER2-
targeted therapies in colorectal cancer are currently in process and have shown promising results. |
