Prognostički značaj serumske koncentracije HER2/ECD u bolesnica s lokaliziranim tumorima dojke

Badžek, Saša (2012) Prognostički značaj serumske koncentracije HER2/ECD u bolesnica s lokaliziranim tumorima dojke. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Scope of the problem HER2 overexpression is well established risk factor of worse prognosis in metastatic and early breast cancer. HER2 positivity can be determined from tumor tissue by immunohistochemical staining or by fluorescent in situ hybridization, or from serum by measuring concentration of HER2 receptor extracellular domain (HER2/ECD). HER2/ECD correlates well with worse prognosis in metastatic and locally advanced (stage III) disease if serum concentration is >15 ng/ml, but there is no consistent data for patients with early breast cancer. Study design and results 41 patients with stage I and II breast cancer and 52 healthy controls were included into the study. HER2/ECD was determined before surgery and correlated with HER2/neu overexpression, Ki67, hormone receptor status and disease stage, and compared with value in healthy controls. Mean serum HER2/ECD concentration in patients was 8.62 ng/ml and 5.78 ng/ml in controls, and the difference was statistically significant (p=0.000061). The best diagnostic cut-off value was 7.7 ng/ml, with 76.92% sensitivity and 72.92% specificity. Positive predictive value of the test was 69.77% and negative predictive value was 79.55%, with 74.71% of patients correctly classified. Serum HER2/ECD correlated with hormone receptors status, and no correlation with histological overexpression has been observed. Conclusion Serum HER2/ECD concentration of ≥7.7 ng/ml has possible diagnostic value in stage I and II breast cancer. It should not be used as a determinant of HER2 positivity. Prognostic significance of HER2/ECD in early breast cancer, its correlation with hormone receptor status, and interconnection between hormone receptors and HER2 receptor signaling should be further analyzed, since it may have therapeutic implications.

Abstract in Croatian

Prikaz problema Pojačana ekspresija HER2 receptora je dobro poznat rizični čimbenik lošije prognoze u bolesnica s metastatskim i lokaliziranim rakom dojke. HER2 pozitivnost se može odrediti iz tumorskog tkiva imunohistokemijskim bojenjem ili fluorescentnom in situ hibridizacijom, ili iz seruma mjerenjem koncentracije vanstanične domene HER2 receptora. Serumska koncentracija HER2/ECD dobro korelira s lošijom prognozom u bolesnica s metastatskom i lokalno uznapredovalom bolešću (klinički stadij III) ukoliko je izmjerena koncentracija iznad 15 ng/ml, ali ne postoje konzistetntni podaci za bolesnice s lokaliziranim tumorima kliničkog stadija I i II. Dizajn istraživanja i rezultati U istraživanje je uključena 41 bolesnica s rakom dojke kliničkog stadija I i II, te 52 zdrave žene odgovarajućih demografskih osobina. Serumska koncentracija HER2/ECD određena je prije kirurškog zahvata i korelirana s histološkom izraženošću HER2/neu, proliferacijskim indeksom Ki67, statusom hormonskih receptora i kliničkim stadijem bolesti, te uspoređena sa serumskom koncentracijom u zdravih kontrola. Srednja koncentracija HER2/ECD u bolesnica bila je 8,62 ng/ml, u kontrola 5,78 ng/ml, a razlika je bila statistički značajna (p=0,000061). Kao najbolja „cut-off“ vrijednost izračunata je koncentracija od 7,7 ng/ml, s osjetljivošću od 76,92% i specifičnošću od 72,92%. Pozitivna prediktivna vrijednost testa bila je 69,77%, a negativna prediktivna vrijednost testa 79,55%, sa 74,71% ispravno svrstanih bolesnica. Serumska koncentracija HER2/ECD pozitivno je korelirala sa statusom hormonskih receptora, dok nije uočena korelacija s histološkom ekspresijom HER2/neu. Zaključak Serumska koncentracija HER2/ECD od ≥7,7 ng/ml možda ima vrijednost u dijagnostici raka dojke kliničkog stadija I i II. Zaseban je loš prognostički čimbenik kod bolesnica s lokaliziranim rakom dojke i ne treba se koristiti kao mjerilo histološke HER2 pozitivnosti. Potrebno je dodatno istražiti korelaciju s ekspresijom hormonskih receptora, kao i povezanost unutarstanične signalizacije hormonskih i HER2 receptora, obzirom da može imati terapijske implikacije.

Item Type: Thesis (PhD)
Mentors:
Mentor
Lesko Kelović, Vesna
Departments: Izvan medicinskog fakulteta
Depositing User: dr.med. Helena Markulin
University: Sveučilište u Zagrebu
Institution: Medicinski fakultet
Number of Pages: 82
Status: Unpublished
Creators:
CreatorsEmail
Badžek, SašaUNSPECIFIED
Date: 12 March 2012
Date Deposited: 27 May 2014 11:12
Last Modified: 27 May 2014 11:12
Subjects: WP Gynecology > WP 800-910 Breast > WP 840-870 Breast Diseases. Neoplasms
Related URLs:
    URI: http://medlib.mef.hr/id/eprint/2111

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