Folate Receptor Alpha Expression in Triple Negative Breast Cancer

Cilj istraživanja: Folatni receptor alfa (FRα) je protein koji je prekomjerno eksprimiran u različitim tumorima. Pokazao se kao potencijalna prognostička i terapeutska meta, ponajprije u karcinomima ovarija i pluća, no isto tako i u karcinomima dojke. Studije su pokazale da je njegova ekspresija viša u trostruko negativnim karcinomima (TNBC) u odnosu na druge fenotipove karcinoma dojke. Stoga je cilj ove studije bio ispitati ekspresiju FRα unutar kohorte pacijenata oboljelih od TNBC, a u korelaciji sa kliničko-patološkim obilježjima i prognostičkim čimbenicima. Materijali i metode: Učinjeno je imunohistokemijsko bojenje poliklonalnim protutijelom FRα na arhivskim parafinskim blokovima pacijenata s TNBC Kliničkog zavoda za patologiju i sudsku medicinu Kliničkog bolničkog centra Osijek. Kao pozitivan rezultat ocijenilo se membransko bojenje te se ekspresija izrazila pomoću H-score metode. Statističkim metodama korelirala se ekspresija FRα s kliničko-patološkim parametrima i ishodom, odnosno sveukupnim preživljenjem (OS) i preživljenjem bez povrata bolesti (BCFI). Rezultati: Većina ispitanica imala je pozitivnu ekspresiju FRα (85 %, 78/92). Dokazana je statistički značajna povezanost ekspresije s histološkim gradusom (Mann Whitney U test, P=0,03) i tipom tumora (P=0,02). Pearsonovim koeficijentom korelacije uočilo se da uz više vrijednosti proliferacijskog indeksa Ki-67, H-score poprima niže vrijednosti (r = -0,284, P = 0,006). Multivarijatnom regresijskom analizom (Cox regresija, Stepwise metoda) H-score se pokazao kao značajni prediktor koji utječe na vjerojatnosti pojave relapsa bolesti (OR=1,005, P = 0,04). Nije se dokazala statistički značajna povezanost s OS i BCFI. Zaključak: FRα je u velikoj mjeri eksprimiran u TNBC te se, s obzirom na povezanost sa pojedinim kliničko-patološkim parametrima, mogu izdvojiti skupine pacijenata koje bi bile potencijalna meta za nove terapijske mogućnosti u liječenju TNBC.Objectives: Folate receptor alpha (FRα) is a protein that is excessively expressed in various tumours. It is shown to be a potential prognostic and therapeutic target, primarily in ovarian and lung cancer, as well as in breast cancer. Studies have shown that its expression is higher in triple negative breast cancer (TNBC), compared to other breast cancer phenotypes, hence the aim of this study was to examine FRα expression in TNBC patient cohort, in correlation with clinicopathological parameters and prognostic factors. Material and methods: Immunohistochemistry was performed using polyclonal FRα antibody on archival paraffin blocks, from the Department of Pathology and Forensic Medicine, University Hospital Centre Osijek, of patients with TNBC. Membranous staining was deemed positive, and H-score was used to evaluate FRα expression. Statistical analysis correlating FRα expression with clinicopathologic parameters and clinical outcome, overall survival (OS) and disease-free survival (BCFI), were performed. Results: Most cases showed positive FRα expression (85%, 78/92). Statistically significant correlation of expression and histologic grade (Mann Whitney U test, P=0,03), as well as the type of tumour (P=0,02), was found. Using the Pearson coefficient of correlation, it was noticed that with higher Ki-67 proliferation index values, H-score has lower values (r = -0,284, P = 0,006). Multivariant regression analysis (Cox regression, Stepwise method) proved H-score to be a significant predictor that affects the probability of disease relapse. (OR=1,005, P = 0,04). No correlation between FRα expression and OS and BCFI was found. Conclusion: FRα is greatly expressed in TNBC, and given the correlation with clinicopathological parameters, groups of patients could be identified that would be potential targets for new therapeutic perspectives in the treatment of TNBC