ABSTRACT
BACKGROUND: FOXA1 expression is a good prognostic marker for endocrine therapy in hormone-positive breast cancer. We retrospectively examined breast cancer patients with luminal human epidermal growth factor receptor 2 (HER2)-negative tumours, as defined by immunohistochemistry, who received neo-adjuvant chemotherapy (NAC) and investigated the relationship between treatment effects and FOXA1 expression. METHODS: Biopsy specimens from 103 luminal HER2-negative tumours were immunohistochemically examined. FOXA1 effects on chemo-sensitivity were also investigated employing in vitro experiments. RESULTS: FOXA1 and Ki67 expressions independently predicted a pathological complete response (pCR). Knockdown of FOXA1 by siRNA boosted the chemo-effect in oestrogen receptor-positive cells. The Cox hazards model revealed a pCR to be the strongest factor predicting a good patient outcome. CONCLUSIONS: Our present study showed low FOXA1 expression to be associated with a good response to NAC in luminal HER2-negative breast cancer. Improved outcomes of these patients suggest that NAC should be recommended to patients with low FOXA1 tumours.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Gene Expression , Hepatocyte Nuclear Factor 3-alpha/metabolism , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Bridged-Ring Compounds/administration & dosage , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/mortality , Cell Line, Tumor , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Disease-Free Survival , Docetaxel , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Gene Knockdown Techniques , Hepatocyte Nuclear Factor 3-alpha/genetics , Humans , Kaplan-Meier Estimate , Ki-67 Antigen/metabolism , Middle Aged , Neoadjuvant Therapy , Proportional Hazards Models , Receptor, ErbB-2/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Taxoids/administration & dosage , Treatment Outcome , Young AdultABSTRACT
AIMS: To determine the relationship between lymphatic invasion detected by D2-40 immunostaining and nodal metastasis in squamous cell carcinoma (SCC) of the cervix. METHODS AND RESULTS: Seventy-five cases of FIGO stage IB to IIB SCC of the cervix, treated by radical hysterectomy and lymph node dissection, were examined. Immunohistochemistry for D2-40 was performed. Overestimation of lymphatic invasion on conventional histological examination was demonstrated by assessment of D2-40 immunoreactivity in 22 cases. A significant difference in lymphatic invasion detected by D2-40 immunostaining was found between the metastatic group (30 cases) and the non-metastatic group (45 cases) (P < 0.001). A grading system (grade 0-2) of lymphatic invasion according to D2-40 immunostaining was devised. Subsequently, the frequency of nodal metastasis significantly increased in accordance with the grade of lymphatic invasion (P < 0.001) and in eight cases with grade 2, seven cases (87.5%) had nodal metastasis. CONCLUSIONS: In cervical SCC, a grading system for lymphatic invasion according to D2-40 immunostaining is useful for the prediction of nodal metastasis and grade 2 lymphatic invasion is a strong predictor of nodal metastasis.
