TITLE:
Prognostic and Clinicopathological Value of the Expression of FOXC2 & YKL-40 in Carcinoma of the Breast, an Immunohistochemical Study
AUTHORS:
Enas M. Fouad, Abla S. Mahmoud, Rham Z. Ahmed, Basant Sh El Shafaay, Ramadan Mahmoud, Gamal Osman, Mohamed Farouk Amin, Loay M. Gertallah, Manar A. Bessar
KEYWORDS:
Carcinoma of the Breast, FOXC2, YKL-40, Prognosis, Immunohistochemistry
JOURNAL NAME:
Advances in Breast Cancer Research,
Vol.7 No.3,
June
6,
2018
ABSTRACT: Background: Breast cancer is considered the commonest and the most fatal female
cancer worldwide. There is to an urgent need for discovering recent therapies
to identify patient prognosis and improve treatment strategies. Fork-head Box
C2 (FOXC2) is a transcription factor which is a key regulator of cancer stem
cells (CSC) properties and epithelial mesenchymal transition (EMT) e.g. cancer
initiation, metastatic capacity, and resistance to chemotherapy. FOXC2 roles in
CSCs properties and EMT regulation in breast cancer needs detailed studies.
YKL-40 is known as chitinase-3-like-1 belongs to a family of mammalian proteins
that have an amino acid sequence which is similar to the 18-glycosyl hydrolase
bacterial chitinases group. Recent studies have found aberrant YKL-40 elevated
expression in cancer of various organs, so it may be used as a recent
prognostic biomarker for patients with breast cancer. Former researchers have
assessed the expression of FOXC2 & YKL-40 separately in cancer patients and
relations to prognosis of patients; however, no studies assessed them together
in breast cancer patients and the previous results were inconclusive.
Accordingly, our study aimed at evaluation of immunohistochemical expressions
of FOXC2 & YKL-40 in carcinoma of the breast in a trial to clarify the
relation among their expressions, clinicopathological parameters and recurrence
of the disease after successive therapy and patients’ prognosis. Methods: we
have evaluated expressions of FOXC2 & YKL-40 in sections from 50 paraffin
blocks of carcinoma of the breast using immunohistochemistry. We followed up
our patients for 3 years for assessment of recurrence of the disease after
successive therapy and survival rates. We analyzed the relationship between
their combined expression clinicopathological and prognostic parameters. Results: high FOXC2 expression was associated with older age of the patient (p = 0.002),
negative ER (p = 0.009), & PR (p = 0.008), positive HER2neu (p = 0.02),
aggressive molecular subtype, higher grade of the tumor (p = 0.03), high
incidence of distant metastasis (p = 0.011), high incidence of lymph node
metastasis, higher KI labeling index, advanced stage, (p expression was positively correlated with older age of the
patient (p = 0.002), negative ER (p = 0.03), & PR (p = 0.04), positive
HER2neu (p = 0.02), higher grade of the tumor (p = 0.003), high incidence of
distant metastasis (p = 0.04), higher KI labeling index, aggressive molecular
subtype, advanced stage, high incidence of lymph node metastasis (p Conclusion: Higher expression levels of FOXC2 & YKL-40
are markers of poor prognosis in breast cancer.