OBJECTIVETo evaluate the expression of cytokeratins in intraductal proliferative lesions of breast, including usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), ductal carcinoma-in-situ (DCIS) and its role in differential diagnosis.

METHODSNinety two cases of paraffin-embedded lesional breast tissue, 30 cases of frozen samples, cell cultures of hyperplastic ductal cells and 2 invasive ductal carcinoma cell lines (T47D and MCF-7) were used for this study. Immunohistochemistry was performed using EnVision method for 34betaE12, CK8 and CK14.

RESULTSThe percentage of 34betaE12-positivity in paraffin-embedded samples of UDH, ADH, DCIS and invasive ductal carcinoma (IDC) was found to be 95.2%, 33.3%, 19.2% and 12.5% respectively. In frozen tissues, all UDH cases and 55% of IDC cases expressed 34betaE12. The primary UDH cell cultures and T47D cell line were also 34betaE12-positive, whereas MCF7 cell line showed negative staining. The expression rate of CK8 and CK14 in UDH was also different from that in ADH and DCIS.

CONCLUSIONS34betaE12 can be useful in differential diagnosis of intraductal proliferative lesions of the breast. However application of this cytokeratin stain in intraoperative frozen sections is relatively limited. The expression patterns of CK8 and CK14 are also helpful in the differential diagnosis of similar lesions.

Breast ; chemistry ; pathology ; Breast Neoplasms ; chemistry ; diagnosis ; pathology ; Carcinoma, Ductal, Breast ; chemistry ; diagnosis ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; chemistry ; diagnosis ; Cell Line, Tumor ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia ; Keratins ; analysis ; Precancerous Conditions ; chemistry ; pathology

We have studied the patterns of P-glycoprotein expression before and after 3 cycles of induction chemotherapy (5-fluorouracil, adriamycin and cyclophosphamide) using immunohistochemically stained paraffin-embedded specimen of 28 patients with locally advanced breast cancer. The frequency of P-glycoprotein expression in untreated breast cancer turned out to be very low: only one out of 28 untreated, biopsy specimen at the time of diagnosis was positive. The frequency of P-glycoprotein expression was markedly increased from 9.1% before chemotherapy to 63.6% after induction chemotherapy (p = 0.006). After 3 cycles of induction chemotherapy, 25 patients had obtained clinical response to chemotherapy (4, CR; 21, PR). Eleven out of 25 tumors (44%) showing clinical response and all three tumors (100%) with minimal response have expressed P-glycoprotein. One out of 6 patients (16.7%) with microscopic residual tumor seen in mastectomy specimen expressed P-glycoprotein, whereas 13 of 22 patients (59.1%) with gross residual tumor showed the presence of P-glycoprotein (p = 0.08). The frequency of intrinsic P-glycoprotein expression in untreated breast cancer was quite low, but approximately half of the patients do acquire P-glycoprotein expression during the cycles of induction chemotherapy. Therefore, the results suggest that the immunohistochemical detection of P-glycoprotein on residual tumor cells after induction chemotherapy can predict acquired drug resistance in breast cancer.
Adult ; Aged ; Breast Neoplasms/chemistry/*drug therapy/pathology ; Breast Neoplasms/chemistry/*drug therapy/pathology ; Drug Resistance ; Drug Resistance ; Female ; Human ; Immunohistochemistry ; Membrane Glycoproteins/*analysis ; Middle Age ; P-Glycoprotein

OBJECTIVETo evaluate the standards of HER2 immunohistochemistry (IHC) interpretation in invasive micropapillary carcinoma of the breast (IMPC).

METHODSHER2 expression in 60 cases of IMPC was evaluated by IHC and fluorescence in situ hybridization (FISH) using TMA-based techniques. The characteristics between cases with HER2 IHC and HER2 gene amplification results were compared.

RESULTSUsing 2007 American Society of Clinical Oncology/College of American Pathologist (ASCO/CAP) criteria, among the 52 cases that were successfully stained by IHC, 40 were HER2 IHC negative and 12 were equivocal (2+). Fifteen cases of HER2 IHC 0 were negative for amplification by FISH. Twenty-five cases with IHC 1+ were tested by FISH; and of these, one showed HER2 amplification, 2 were equivocal, and the others were not amplified. All cases of IHC 2+ showed HER2 amplification by FISH. IHC staining of HER2 was located at cell-cell membrane or basolateral membrane of micropapillary structure, but not in the cytoplasmic membrane facing the stroma in all 13 cases which were HER2 amplified, including 12 showing very strong staining and one showing moderate staining. Among the 37 non amplified HER2 cases, 22 showed IHC staining at cell-cell membrane or basolateral membrane (including 15 weak staining and 7 moderate staining).

CONCLUSIONSHER2 IHC detection in IMPC is characterized by staining at cell-cell membrane or basolateral membrane of the micropapillary structure, and absence of staining in the cytoplasmic membrane. It is suggested that interpretation of HER2 IHC staining should be based on membrane staining intensity, but not the completeness of the membrane staining in IMPC. It is suggested to determine the HER2 gene amplification status by using FISH when IHC staining shows moderate or strong intensity.

Adenocarcinoma, Papillary ; chemistry ; pathology ; Breast Neoplasms ; chemistry ; pathology ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Receptor, ErbB-2 ; analysis

OBJECTIVETo assess the clinicopathological features of atypical cystic duct (ACD) as a precancerous lesion of the breast.

METHODSWhole mammary gland serial sections were performed on 200 cases of breast cancer without pre-operative biopsy (prior operation, fine needle aspiration or needle biopsy were routinely performed in each case). The clinicopathological findings and immunohistochemical features of ACD were investigated.

RESULTSForty-four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P=0.001). A number of ACD lesions displayed a histological transition to adjacent ductal carcinoma in-situ. In 16 of 44 (36%) patients with ACD, carcinoma cells stained positive for p53. In 12 of these 16 cases (75%), ACD cells also stained positive for p53 protein (P=0.001). Myoepithelial cells of ACD appeared attenuated and stained strongly for alpha-smooth muscle actin. There was no correlation between the ACD-present group and the ACD-absent group in tumor size, nodal metastasis, and immunostaining patterns of estrogen receptor (ER), progesterone receptor (PR), p53, c-erbB-2 and Ki-67 labeling index of cancerous tissues. All 44 ACD lesions showed a negative staining of c-erbB-2, regardless of the staining result in their corresponding carcinomas. The mean Ki-67 labeling index of ACD lesions was low.

CONCLUSIONSACD is frequently associated with breast cancer. It may represent a precancerous mammary lesion, supported by the frequent histological continuum between ACD and malignancy, and simultaneous p53 over-expression present in both ACD and its corresponding breast carcinoma.

Biomarkers, Tumor ; analysis ; Breast Neoplasms ; chemistry ; pathology ; surgery ; Carcinoma in Situ ; chemistry ; pathology ; surgery ; Carcinoma, Ductal, Breast ; chemistry ; pathology ; surgery ; Female ; Humans ; Precancerous Conditions ; chemistry ; pathology ; surgery ; Receptors, Estrogen ; analysis ; Receptors, Progesterone ; analysis

Breast Neoplasms ; chemistry ; pathology ; Carcinoma, Ductal, Breast ; chemistry ; pathology ; Electrophoresis, Polyacrylamide Gel ; methods ; Female ; Fluorescent Dyes ; Gelatin ; metabolism ; Humans ; Matrix Metalloproteinase 2 ; analysis

As a common malignant tumor, breast cancer has seriously affected women's physical and psychological health even threatened their lives. Breast cancer has even begun to show a gradual trend of high incidence in some places in the world. As a kind of common pathological assist diagnosis technique, immunohistochemical technique plays an important role in the diagnosis of breast cancer. Usually, Pathologists isolate positive cells from the stained specimen which were processed by immunohistochemical technique and calculate the ratio of positive cells which is a core indicator of breast cancer in diagnosis. In this paper, we present a new algorithm which was based on modified watershed algorithm and concavity points searching to identify the positive cells and segment the clustered cells automatically, and then realize automatic counting. By comparison of the results of our experiments with those of other methods, our method can exactly segment the clustered cells without losing any geometrical cell features and give the exact number of separating cells.
Algorithms ; Breast Neoplasms ; pathology ; Cell Separation ; Epithelial Cells ; chemistry ; pathology ; Female ; Humans ; Image Processing, Computer-Assisted ; Immunohistochemistry ; methods

OBJECTIVEIn order to explore the correlation between the centrosome aberration and oncogenesis of the breast carcinoma, the expression of alpha-tubulin and gamma-tubulin proteins in breast precancerous lesions, ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC) was investigated.

METHODSQuantitative immunofluorescence analysis was performed for measuring centrosome proteins by FITC-labeled monoclonal anti-alpha and anti-gamma-tubulin antibodies in 90 cases with precancerous lesions, DCIS and IDC of the breast, respectively. Normal breast tissue from 30 cases were taken as control group.

RESULTSThe average of positive (FITC-labeled) cells were 3.2, 11.6, 14.8, 23.1 (alpha-tubulin) and 3.3, 10.7, 14.5, 24.5 (gamma-tubulin) in four groups, respectively. There were significant differences of alpha-tubulin or gamma-tubulin expression among those groups (P = 0.000), respectively. The highest expression quantity was in IDC group and the lowest was in normal breast tissue. Their expression was significantly associated with cellular proliferation and differentiation.

CONCLUSIONThere is over-expression of the centrosome tubulin protein in the precancerous stage of the breast. The centrosome aberration may play an important role during the crucial early step of oncogenesis and it may promote the cellular cancerization or transformation into malignancy. Quantitative immuno-fluorescence analysis and immunohistochemistry can be complementary each other.

Breast ; chemistry ; pathology ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; Cell Differentiation ; Cell Proliferation ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Precancerous Conditions ; metabolism ; pathology ; Tubulin ; analysis

Antigens, CD20 ; analysis ; Biopsy, Needle ; Breast Neoplasms ; chemistry ; pathology ; Female ; Humans ; Lymphoma, B-Cell, Marginal Zone ; chemistry ; pathology ; Middle Aged ; Nipples ; pathology

Breast Neoplasms ; chemistry ; diagnosis ; pathology ; Carcinoma, Ductal, Breast ; chemistry ; diagnosis ; pathology ; Carcinoma, Papillary ; chemistry ; diagnosis ; pathology ; Diagnosis, Differential ; Female ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2 ; analysis ; Receptors, Estrogen ; analysis

INTRODUCTIONThe specificity of conventional magnetic resonance (MR) imaging is lower than its high sensitivity. Diffusion-weighted imaging (DWI), based on alterations in the microscopic motion of water molecules, promises improved specificity for breast MR imaging. In this study, we aimed to determine the diagnostic potential of DWI to differentiate between benign and malignant breast lesions and normal breast tissue.

METHODSDynamic contrast-enhanced breast MR imaging and DWI were applied to 108 women. Apparent diffusion coefficient (ADC) values were obtained for normal breast tissue (n = 183), benign lesions (n = 66) and malignant lesions (n = 58). The results were compared with the patients' final diagnoses.

RESULTSMean ADC values for benign and malignant breast lesions were 1.04 × 10-3 ± 0.29 × 10-3 mm2/s and 2.00 × 10-3 ± 0.55 × 10-3 mm2/s, respectively (p = 0.001, Student's t-test), while that for normal breast tissue was 1.78 × 10-3 ± 0.33 × 10-3 mm2/s. With a cut-off value of 1.46 × 10-3 mm2/s for ADC in receiver operating characteristic analysis, 95% sensitivity and 85% specificity were achieved for differentiating between benign and malignant lesions.

CONCLUSIONDWI of the breast can help differentiate benign and malignant breast lesions from normal breast tissue. DWI, which can be easily introduced into standard breast MR imaging protocols without increasing imaging times, promises to increase the accuracy of breast MR imaging without contrast media. However, its clinical value will depend on the standardisation of b-values and other technical parameters in larger future study series.

Adult ; Aged ; Breast ; pathology ; Breast Neoplasms ; diagnosis ; pathology ; Diffusion ; Diffusion Magnetic Resonance Imaging ; methods ; Female ; Humans ; Middle Aged ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity ; Water ; chemistry ; Young Adult