INTRODUCTIONThis study aimed to analyse the concordance rate, sensitivity, specificity, positive predictive value (PPV) and negative predictive value of core needle biopsy (CNB) and subsequent surgical specimen (SS) in assessing levels of oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2/neu). It also evaluated the revised American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for ER/PgR positivity.

METHODSWe analysed the breast cancer database of KK Women's and Children's Hospital, Singapore, from 1 June 2005 to 30 December 2012. Invasive breast cancer patients who had CNB and subsequent SS were included.

RESULTSA total of 560 patients were included. The concordance of ER, PgR and HER2/neu positivity between CNB and SS was 96.1%, 89.1% and 96.8%, respectively. When the 'ER ≥ 10% positive' group was compared with the 'ER ≥ 1% positive' group, specificity increased from 79.7% to 92.5% and PPV increased from 93.9% to 97.5%. When the 'PgR ≥ 10% positive' group was compared with the 'PgR ≥ 1% positive' group, specificity increased from 84.2% to 89.3% and PPV improved from 89.7% to 92.9%. The revised ASCO/CAP guidelines decreased discordant results by > 50% for ER and by 18.2% for PgR.

CONCLUSIONCNB has high concordance with SS in the evaluation of the molecular profile of invasive breast cancer. Thus, molecular evaluation does not need to be repeated with SS except for ER-, PgR- and HER2/neu-negative CNB results. The revised ASCO/CAP guidelines resulted in more precise ER and PgR status on CNB.

Automation ; Biopsy, Large-Core Needle ; Breast Neoplasms ; diagnosis ; pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Predictive Value of Tests ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Sensitivity and Specificity ; Singapore

OBJECTIVETo investigate the expression of p16INK4a protein in breast cancer and analyze its clinical significance.

METHODSA total of 132 surgical specimens of primary breast cancer obtained between 2014 and 2015 were examined for expressions of ER, PR, CK5/6, Her-2 and p16INK4a proteins using immunohistochemistry.

RESULTSThe breast cancer samples were classified into 5 molecular subtypes, namely Luminal A (58 cases), Luminal B (32 cases), Her-2-positive (21 cases), basal-like (12 cases) and normal-like (9 cases) types. p16INK4a expression was negative in 7/132 (5.30%) cases, weakly positive in 15/132 (11.36%) cases, positive in 40/132 (30.30%) cases, and strongly positive in 70/132 (53.03%) cases. When categorizing negative and weakly positive cases into negative group and the positive and strongly positive cases into positive group, the total negative and positive expression rates of p16INK4a were 16.67% (22/132) and 83.33% (110/132) in the carcinoma tissues. Statistical analysis showed the expression intensity of p16INK4a differed significantly between the age groups (P<0.05) but was not significantly correlated with ER, PR, Her-2, molecular subtypes or metastasis of the tumors.

CONCLUSIONThe compensatory high expression of p16INK4a is the main mechanism of cell cycle deregulation in invasive breast cancer and can be an important specific molecular marker for invasive breast cancer.

Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; classification ; diagnosis ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Female ; Humans ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo investigate the expression of long non-coding RNA HOTAIR in the plasma of breast cancer patients and its value in the diagnosis of breast cancer.

METHODSHOTAIR levels were measured in 24 tumor tissues and 70 plasma samples from breast cancer patients using quantitative real-time PCR. The correlations of plasma HOTAIR level with the clinicopathological features of the patients were analyzed. A multivariate logistic regression model was established to analyze the value of plasma HOTAIR in comparison with plasma CA153 and CEA levels for breast cancer diagnosis. We further detected HOTAIR levels in the plasma and breast cancer tissues of 24 patients before and after operation and investigated their correlation.

RESULTSBreast cancer patients had increased expressions of HOTAIR in the tumor tissues and plasma, and plasma HOTAIR level was significantly correlated with estrogen receptor (ER) level (P=0.004) and lymph node metastasis (P=0.010). Receiver operating characteristic (ROC) curve and the multivariable logistic regression model showed that the area under ROC curve (AUC) of plasma HOTAIR was 0.82 (P<0.001) for breast cancer diagnosis with a diagnostic sensitivity and a specificity of 73.3% and 93.3%, respectively. The diagnostic power and specificity of plasma HOTAIR was much higher than those of CA153 (AUC=0.66, P=0.030) and CEA (AUC=0.52, P=0.001), and the combination of the 3 markers further enhanced the diagnostic power (AUC=0.84) and specificity (96.7%). Plasma HOTAIR level was significantly reduced in the patients after the operation (P<0.0001) and showed a moderate correlation with its expression in tumor tissues (r=0.62, P<0.0001).

CONCLUSIONPlasma HOTAIR may serve as a potential biomarker for breast cancer diagnosis.

Biomarkers, Tumor ; blood ; Breast Neoplasms ; blood ; diagnosis ; Carcinoembryonic Antigen ; blood ; Female ; Humans ; Logistic Models ; Lymphatic Metastasis ; Mucin-1 ; blood ; Prognosis ; RNA, Long Noncoding ; blood ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Receptors, Estrogen ; metabolism ; Sensitivity and Specificity

OBJECTIVETo investigate neuroendocrine differentiation and Wilms' tumor protein-1 (WT-1) expression in breast mucinous carcinoma and their clinicopathological significance.

METHODSThe clinicopathological data of 65 patients with breast mucinous carcinoma, including 31 cases of mixed mucinous carcinoma, 23 cases of hypocellular pure mucinous carcinoma and 11 cases of hypercellular pure mucinous carcinoma, admitted in Taizhou Hospital from January 2010 to June 2015 were retrospectively reviewed. The expression of neuroendocrine markers and WT-1 was detected by immunohistochemistry staining in all cases.

RESULTSThe mixed mucinous carcinomas and hypercelluar pure mucinous carcinomas had higher incidence of axillary lymph node metastasis and human epidermal recepter 2 (HER-2) positive than hypocellular pure mucinous carcinoma (all (P<0.01). However, the difference was not significant between mixed mucinous carcinomas and hypercellular pure mucinous carcinomas (all P>0.05). The expression of neuroendocrine marker was stronger in hypercellular mucinous carcinoma than that in mixed mucinous carcinoma and hypocellular mucinous carcinoma (all (P<0.05), but the difference was not statistically significant between mixed mucinous carcinoma and hypocellular pure mucinous carcinoma (P>0.05). The expression of WT-1 was weaker in mixed mucinous carcinoma than that in hypercellular and hypocellular pure mucinous carcinoma(all (P<0.05), but the difference was not statistically significant between hypercellular and hypocellular pure mucinous carcinoma (P>0.05). The mucinous carcinomas with lymph node metastasis had lower expression of neuroendocrine markers than those without lymph node metastasis ((P<0.01). The expression of WT-1 in breast mucinous carcinoma with lymph node metastasis trended lower than that in those without lymph node metastasis, but the difference was not statistically significant (P>0.05).

CONCLUSIONHypercellular pure mucinous breast carcinoma has higher rates of lymph node metastasis and HER-2 amplification than hypocellular pure mucinous carcinoma, the sub-classification of breast pure mucinous carcinoma should be considered. Neuroendocrine differentiation and WT-1 expression may be helpful in distinguishing the subtypes of breast mucinous carcinoma. Breast mucinous carcinoma with neuroendocrine differentiation trends to have less lymph node metastasis.

Adenocarcinoma, Mucinous ; classification ; diagnosis ; pathology ; Axilla ; Breast Neoplasms ; classification ; diagnosis ; pathology ; Female ; Humans ; Immunohistochemistry ; Incidence ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Neuroendocrine Tumors ; diagnosis ; pathology ; Receptor, ErbB-2 ; metabolism ; Retrospective Studies ; WT1 Proteins ; metabolism

Adult ; Breast Neoplasms ; diagnosis ; metabolism ; surgery ; Female ; Humans ; Nipples ; pathology ; surgery ; Ultrasonography ; methods

OBJECTIVE: To evaluate the sonographic features of invasive apocrine carcinoma (IAC) of the breast. MATERIALS AND METHODS: This study included five pathologically proven cases of IAC, and their sonographic features were retrospectively analyzed according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon. RESULTS: All five lesions involved the left breast and were seen as irregularly shaped masses. All lesions, except one, had a parallel orientation to the chest wall. All five lesions showed noncircumscribed margins and heterogeneous echotexture; however, they showed various posterior features. One lesion had edema as an associated feature. Sonographic assessments were classified as BI-RADS category 4 in all five cases. CONCLUSION: Invasive apocrine carcinoma sonographic findings are difficult to differentiate from those of invasive ductal carcinoma of no special type.
Aged ; Apocrine Glands/pathology/ultrasonography ; Breast Neoplasms/*diagnosis/pathology/ultrasonography ; Carcinoma/*diagnosis/pathology/ultrasonography ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Positron-Emission Tomography ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tomography, X-Ray Computed ; Tumor Suppressor Protein p53/metabolism

OBJECTIVETo investigate the expression of high-molecular-weight keratins CK5/6, CK14, estrogen receptor (ER) and progesterone receptor (PR) in differential diagnosis of simple ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH) and low-grade ductal carcinoma in situ (low-grade DCIS) .

METHODSThe clinicopathological data of twenty cases of atypical ductal epithelial hyperplasia (ADH) with focal cancerization changed into low-grade DCIS diagnosed at Tianjin Medical University Cancer Institute and Hospital between January 2013 and February 2014 were reviewed and analyzed. The expressions of CK5/6, CK14, ER and PR were detected by immunohistochemistry.

RESULTSPositive expressions of CK5/6 and CK14 were seen in UDH showing a mosaic pattern, while negative expression in ADH and low-grade DCIS. In addition, CK5/6 and CK14 were positively expressed in the myoepithelial cells of UDH, ADH and low-grade DCIS. Positive expressions of ER and PR were observed in UDH, ADH and low-grade DCIS. But they presented diffuse and homogeneous strong positive expression in ADH and variable positive expression in UDH.

CONCLUSIONIn the intraductal proliferative lesions of the breast, the use of combined detection of the expression of CK5/6, CK14, ER and PR is of practical significance in the differential diagnosis of UDH, ADH and low-grade DCIS.

Breast ; metabolism ; pathology ; Breast Neoplasms ; diagnosis ; metabolism ; Carcinoma, Ductal, Breast ; diagnosis ; metabolism ; Carcinoma, Intraductal, Noninfiltrating ; diagnosis ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia ; diagnosis ; metabolism ; Immunohistochemistry ; Keratin-14 ; metabolism ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo explore the relationship between a proliferation-inducing ligand (APRIL) expression in primary tumor foci of breast cancer and the patients' prognosis.

METHODSParaffin sections of surgical specimens were retrospectively collected from 130 stage I-III breast cancer patients who received surgery between January 2000 and December 2002 in our hospital. Immunohistochemistry was used to assess APRIL expression intensity in the tumor cells and density of interstitial APRIL-positive cells, and their association was analyzed with the density of interstitial CD4⁺ and CD8⁺ cells and with the histopathologic features, overall survival (OS), and disease-free survival (DFS) of the patients.

RESULTSAPRIL positive staining was found in the cytoplasm of the tumor cells, interstitial cells, and the extracellular matrix. APRIL intensity in the tumor cells was positively correlated with the density of interstitial APRIL-positive cells (P=0.009) and Ki67 (P=0.003). The density of interstitial APRIL-positive cells was positively correlated with the density of interstitial CD4⁺ cells (P<0.001) and CD8⁺ cells (P<0.001). In hormone receptor negative patients (ER- and PR-), multivariate COX regression identified the density of interstitial APRIL-positive cells as a positive prognostic factor for DFS (HR=0.313, 95% CI=0.107-0.920, P=0.035). CONCLUSIONSl APRIL is widely expressed in the interstitial immune cells in breast cancer. APRIL staining intensity in the tumor cells is positively correlated with tumor proliferation, indicating that the immune cells might promote tumor proliferation by secreting APRIL. A greater density of interstitial APRIL-positive cells is associated with a good prognosis in hormone receptor-negative patients.

Breast Neoplasms ; diagnosis ; metabolism ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Cell Transformation, Neoplastic ; Cytoplasm ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Prognosis ; Retrospective Studies ; Tumor Necrosis Factor Ligand Superfamily Member 13 ; metabolism

OBJECTIVETo investigate the expressions of FOXC1 and matrix metalloproteinase 7 (MMP-7) in different molecular subtypes of breast cancer and their association with clinicopathological characteristics of the disease.

METHODSBased on immunohistochemical results of ER, PR, HER2, CK5/6, CK14 and EGFR, 105 breast cancer patients were classified as 4 subtypes: luminal, HER2 positive, basal-like subtype (BLs) and normal breast-like subtype (NBLs). The association of FOXC1 and MMP-7 expressions with clinicopathological parameters in different molecular subtypes was analyzed.

RESULTSOut of 105 patients with breast cancer, the subtypes of luminal, HER2 positive, BLs and NBLs accounted for 52.4% (55/105), 16.2% (17/105), 17.1%(18/105) and 14.3% (15/105), respectively. Patients with luminal and/or NBLs subtypes had significantly higher 5-year survival rate than those with HER2 positive and/or BLs did (log-rank=22.161, P<0.01). The overall positive expression rate of FOXC1 was 26.7% (28/105) and the expression was higher in BLs patients than that in other subgroups (χ²=30.108, P<0.01). The expression of FOXC1 was correlated with histological grade, tumor size, distant metastasis and 5-year survival rate of breast cancer. The overall positive expression rate of MMP-7 was 67.6% (71/105) and the expression of MMP-7 was also higher in BLs patients than that in other molecular subtypes (χ²=11.328, P<0.05). The positive expression of MMP-7 was correlated with metastasis in ipsilateral axillary lymph nodes, distant metastasis and 5-year survival rate of the patients. FOXC1 was correlated with MMP-7 (r=0.325, P<0.01).

CONCLUSIONPatients with luminal and/or NBLs breast cancer have more favorable prognosis than those with HER2 positive and/or BLs subtypes. The expressions of FOXC1 and MMP-7 are closely correlated with the clinicopathological features of breast cancer patients.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; classification ; diagnosis ; pathology ; Female ; Forkhead Transcription Factors ; metabolism ; Humans ; Matrix Metalloproteinase 7 ; metabolism ; Middle Aged ; Prognosis

OBJECTIVETo evaluate the association between high sensitivity C-reactive protein (hsCRP) and breast cancer incidence among the non-diabetic females in a large-scale cohort study in Kailuan group.

METHODSThe Kailuan cohort was established on May 1, 2006. Baseline information on demography, lifestyle, medical history, and anthropometry, i.e., body height and weight, were collected during the baseline interview, and breast cancer incidence, mortality and other related outcome information were obtained by follow-up every two years and the related health condition database information were collected every year. Multivariable Cox proportional-hazards regression model was used to calculate the hazard ratios (HRs) and 95%CI (confidence interval) between the level of hsCRP at baseline interview and breast cancer incidence adjusted for age group, body mass index (BMI), marital status (married and single) and tobacco smoking (smokers and non-smokers) when appropriate.

RESULTSBy Dec 31, 2011, a total of 17 402 females were enrolled in the cohort. There were 85 286 person-years of follow-up with a mean follow-up period of (58.81 ± 4.52) months. A total of 75 incident breast cancer cases were collected. Subjects with the highest level (>3 mg/L) of hsCRP at baseline interview were associated with a significantly increased risk of breast cancer (adjusted HR = 1.80, 95%CI = 1.03-3.15) compared with those with the lowest level (<1 mg/L).

CONCLUSIONSElevated levels of hsCRP at baseline interview may be associated with an increased risk of breast cancer among non-diabetic females. Further follow-up and etiological exploration will help to evaluate the association between the hsCRP level and the risk of breast cancer more reliably.

Body Mass Index ; Breast Neoplasms ; diagnosis ; epidemiology ; metabolism ; C-Reactive Protein ; metabolism ; Cohort Studies ; Diabetes Mellitus ; Female ; Humans ; Incidence ; Middle Aged ; Proportional Hazards Models ; Prospective Studies ; Risk ; Risk Factors ; Smoking