title: Immunohistochemical co-expression status of cytokeratin 5/6, androgen receptor, and p53 as prognostic factors of adjuvant chemotherapy for triple negative breast cancer.
abstract: Triple negative breast cancer (TNBC) is immunohistochemically characterised by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2). TNBC is known for its poor prognosis and high recurrence probability. There is no effective targeted treatment for TNBC, but only adjuvant chemotherapies. There are two TNBC subtypes, basal-like and non-basal-like, which are defined based on positive cytokeratin (CK) 5/6 and/or epidermal growth factor receptor (EGFR) expression. In particular, CK5/6 expression is reported to correlate with TNBC recurrence. TNBC lacks ER-α expression, but some TNBCs are known to express the androgen receptor (AR). Moreover, although p53 accumulation is detected in various malignant tumors, its influence on adjuvant chemotherapy for patients with TNBC remains unclear. The aim of this study was to assess the combined immunohistochemical expression of CK 5/6, AR, and p53 as a potential prognostic marker of adjuvant chemotherapy for patients with TNBC. The expression of CK5/6, AR, and p53 in formalin-fixed and paraffin-embedded (FFPE) surgical sections from 52 patients with TNBC was analysed by immunohistochemistry (IHC) and the co-expression patterns in individual cells were investigated by immunofluorescent (IF) staining. Low AR expression was correlated with high clinical stage (P < 0.05) and low nuclear grade (P < 0.05). The expression of CK5/6 and p53 did not correlate with clinicopathological features. Patients who needed adjuvant chemotherapy presented the worst prognosis. In particular, when the IHC expression pattern was CK5/6 (-), AR (-), and p53 (+), the disease free survival (DFS) and overall survival (OS) were the worst. On the other hand, patients with AR (+) and p53 (-) TNBC presented a good prognosis. The analysis of the co-expression status of these three markers showed that no cells presented both AR and CK5/6 expression. Furthermore, TP53 mRNA expression was higher in patients with AR-negative TNBC (P < 0.05) and in patients with the worst prognosis (P < 0.05) than in the other patients. These results suggested that, in patients with CK5/6-negative TNBC, AR expression correlated with good prognosis, but p53 accumulation correlated with poor prognosis. The present IHC markers allowed us to predict the post-surgery prognosis of patients with TNBC. In conclusion, TNBCs are heterogeneous. Patients with the CK5/6 (-), AR (-), and p53 (+) TNBC subtype, evaluated by IHC, presented the worst prognosis. These IHC markers will be helpful to follow patients with TNBC.
authors.affiliation: Department of Breast Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Tetsuyo
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Department of Pathology, Nihon University School of Medicine, 30-1 Ohyaguchi-kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan. nakanishi.youko@nihon-u.ac.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Department of Pathology, Nihon University School of Medicine, 30-1 Ohyaguchi-kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Hirotani
authors.affiliation: Department of Pathology, Nihon University School of Medicine, 30-1 Ohyaguchi-kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Fumi
authors.initials: F
authors.lastname: Fuchinoue
authors.affiliation: Department of Breast Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Enomoto
authors.affiliation: Department of Breast Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sakurai
authors.affiliation: Department of Breast Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Sadao
authors.initials: S
authors.lastname: Amano
authors.affiliation: Department of Pathology, Nihon University School of Medicine, 30-1 Ohyaguchi-kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Norimichi
authors.initials: N
authors.lastname: Nemoto
mesh_terms: D000328:Adult; D017024:Chemotherapy, Adjuvant; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053555:Keratin-5 / Q000378:metabolism*; D053553:Keratin-6 / Q000378:metabolism*; D011379:Prognosis; D011944:Receptors, Androgen / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C410798:AR protein, human; D053555:Keratin-5; D053553:Keratin-6; D011944:Receptors, Androgen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: AR; Adjuvant chemotherapy; CK5/6; Prognosis; TNBC; p53