OBJECTIVETo evaluate the immunophenotype conversion of fibroblasts and its clinical significance in the process of breast tumor stromal remodeling.

METHODSCD34, FAP-α, p63 and a-SMA were detected by immunohistochemistry in 273 breast biopsies, including 60 normal breast tissues, 46 atypical ductal hyperplasia (ADH), 60 ductal carcinoma in situ (DCIS), 47 DCIS microinvasive carcinoma (DCIS-MI) and 60 invasive ductal carcinoma (IDC).

RESULTSThe positive expression rates of CD34, FAP-α and α-SMA in the stromal fibroblasts of normal breast tissues were 93.3%, 6.7% and 18.3%, respectively. Those in the stromal fibroblasts of ADH tissues were 95.7%, 4.3% and 10.9%, respectively. Those in the stromal fibroblasts of DCIS tissues were 95.0%, 8.3% and 15.0%, respectively. Those in the IDC tissues were 35.0%, 85.0% and 93.3%, respectively. The expressions of CD34, α-SMA and FAP-α in the stromal fibroblasts of normal, ASH and DCIS breast tissues did not show significant differences (χ(2) = 1.142, P = 0.896). The main immunophenotype of stromal fibroblasts in the tumor-host interface at the invasive front of ADH and DCIS lesions was CD34(+)α-SMA(+)FAP-α(+). There were statistically significant differences in the expression of CD34, α-SMA and FAP-α between IDC and ADH, DCIS and normal breast tissues (χ(2) = 8.351, P < 0.001). The immunophenotype of stromal fibroblasts in the IDC and DCIS-MI breast tissues was CD34(-) α-SMA(+) FAP-α(+).

CONCLUSIONSImmunophenotype conversion from CD34(+) α-SMA(-) FAP-α(-) to CD34(-) α-SMA(+)FAP-α(+) may be a sensitive indicator to judge whether DCIS has microinvasion. Detection of the immunophenotype conversion of stromal fibroblasts may be helpful to determine the presence of microinvasion, and to improve the diagnostic accuracy rate of DCIS.

Breast ; Breast Neoplasms ; immunology ; pathology ; Carcinoma in Situ ; Carcinoma, Ductal, Breast ; Carcinoma, Intraductal, Noninfiltrating ; Fibroblasts ; immunology ; Gelatinases ; metabolism ; Humans ; Hyperplasia ; Immunohistochemistry ; Immunophenotyping ; Membrane Proteins ; metabolism ; Serine Endopeptidases ; metabolism

Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; metabolism ; pathology ; therapy ; Carcinoma in Situ ; metabolism ; pathology ; therapy ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; therapy ; Female ; Humans ; Precision Medicine ; methods

OBJECTIVETo investigate the relationship between partial reversed cell polarity (PRCP) and lymphatic tumor spread in invasive ductal carcinoma (IDC), not othervise specified (NOS).

METHODSImmunohistochemistry (EnVision method) was used to examine the expression of epithelial membrane antigen (EMA) and the reversed cell polarity in 199 cases of IDC.

RESULTSOf the 199 cases, including five cases with micropapillary differentiation,30 cases with PRCP and 164 cases of IDC-NOS (without micropapillary differentiation and/or PRCP), lymphovascular invasion was seen in four (4/5), 13(43.3%) and 30 cases (18.3%) respectively; nodal metastasis was seen in four (4/5), 19 (63.3%) and 56 cases (34.1%) respectively. The rates of lymphovascular invasion and nodal metastasis were significantly higher in IDC with PRCP or IMPC than IDC-NOS (P = 0.00); there was however no significant difference between IDC with PRCP and IMPC for lymphovascular invasion and nodal metastasis (P = 0.18, P = 0.64).

CONCLUSIONSIDC with PRCP, similar to IMPC, is more likely to show lymphovascular invasion and nodal metastasis. Complete or partial reversal of cell polarity may play a significant role in lymphatic tumor spread.

Breast Neoplasms ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Papillary ; metabolism ; pathology ; Cell Polarity ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Mucin-1 ; metabolism ; Neoplasm Invasiveness

Adenocarcinoma, Mucinous ; pathology ; Adult ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma ; pathology ; Carcinoma in Situ ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Fibrocystic Breast Disease ; metabolism ; pathology ; surgery ; Humans ; Hyperplasia ; Lactalbumin ; metabolism ; S100 Proteins ; metabolism

OBJECTIVETo investigate the clinicopathological and immunohistochemical features, diagnosis and differential diagnosis of nipple adenoma of the breast.

METHODSMorphological observation and immunohistochemistry were applied to 18 cases of nipple adenoma with a review of the related literatures.

RESULTSThe neoplasms were localized at nipples or under the areola of breast, adherent to the epidermis, mainly composed of dilated ducts in a tubular appearance associated with fibrotic matrix. The glandular epithelium showed various type of proliferation, forming thick layers or complex structures such as papillae, micropapillae, tufts, fronds, arcades or bridges accompanying with solid or cribriform cell nests. The tumor cells were crowding, lack of an uniform morphology and polarity with intact myoepithelial cells around the ducts. By immunostaining, the glandular epithelium was diffusely positive for 34betaE12, patchily positive for CK5/6, and negative for p53 and c-erbB-2. The myoepithelium, positive for p63, smooth muscle actin and Calponin, was well preserved and outlining the ducts.

CONCLUSIONSNipple adenoma is an infrequent type of benign breast neoplasm, presenting as sclerosing papilloma, papillomatosis or florid sclerosing adenosis. It is easily confused with atypical ductal hyperplasia/low grade ductal carcinoma in situ, invasive ductal carcinoma or low grade adenosquamous carcinoma. A correct diagnosis is based on the peculiar location and morphology of the tumor, and immunohistochemistry is helpful in some cases.

Adenoma ; metabolism ; pathology ; surgery ; Adult ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Adenosquamous ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Humans ; Keratin-5 ; metabolism ; Keratins ; metabolism ; Middle Aged ; Nipples ; metabolism ; pathology ; surgery

OBJECTIVETo study the expression of fascin-1 protein in breast cancer and to evaluate its correlation with clinicopathologic features of the tumor.

METHODSImmunohistochemical EnVision method was performed to evaluate the expression of fascin-1 in 23 cases of normal breast tissues, 69 cases of benign breast lesions, 58 cases of usual ductal hyperplasia (UDH), 61 cases of ductal carcinoma in situ (DCIS) and 221 cases of breast cancer from March 2007 to December 2011.

RESULTSFascin-1 protein expression rates in normal breast tissues, benign breast lesions, UDH, DCIS and breast cancer were 100.0% (23/23), 89.9% (62/69), 13.8% (8/58), 19.7% (12/61), and 42.1% (93/221), respectively. Fascin-1 expression in normal breast tissues and benign breast lesions was significantly higher than those in UDH, DCIS and breast cancer (P < 0.01); Fascin-1 expression in breast cancer was significantly higher than those in UDH and DCIS (P < 0.01). There was a tendency of increased fascin-1 expression in DCIS compared to UDH, but the difference was not statistically significant (P > 0.05). Fascin-1 positive rates in patients with DCIS grade III (26.8%, 11/41) was significantly higher than that in patients with DCIS grade I-II (1/20, P < 0.05). Fascin-1 protein expression in breast cancer increased with increasing histologic grade and clinical stage (P < 0.01). Fascin-1 protein expression was also significantly higher in tumors with negative estrogen receptor (ER) and progestone receptor (PR) status and > 3 axillary lymph node metastases compared to tumors that were ER and PR positive and ≤ 3 axillary lymph node metastases (P < 0.01 and P < 0.05, respectively). Logistic regression analysis showed that fascin-1 expression correlated positively with high clinical stage (OR = 1.568, 95% CI = 1.029-2.387, P < 0.05) , but negatively with ER expression (OR = 0.149, 95% CI = 0.079-0.281, P < 0.01) .

CONCLUSIONSFascin-1 is highly expressed in normal breast tissues and benign breast lesions, suggesting that it may be a biological marker of mature mammary ductal epithelium. Fascin-1 protein expression shows a significantly increasing trend from UDH, DCIS to invasive breast cancer, suggesting that fascin-1 plays an important role in breast carcinogenesis and may be a potential target for therapy.

Axilla ; Breast ; metabolism ; pathology ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carrier Proteins ; metabolism ; Estrogen Receptor alpha ; metabolism ; Female ; Humans ; Hyperplasia ; metabolism ; Lymph Nodes ; metabolism ; Lymphatic Metastasis ; Microfilament Proteins ; metabolism ; Receptors, Estrogen ; metabolism

OBJECTIVETo investigate the relationship between positive expression of Her2 and abnormal expressions of beta-catenin and E-cadherin and its implications.

METHODSImmunohistochemistry was used to detect the expressions of Her2, beta-catenin and E-cadherin in 147 samples of human breast carcinoma. The expressions of beta-catenin and E-cadherin were also detected in 19 tissues adjacent to the carcinoma and 17 benign breast lesions as controls.

RESULTSIn breast carcinoma, positive Her2 expression was associated with lymph node metastasis, advanced clinical stage and negative expression of ER and PR (P<0.05). Abnormal beta-catenin expression was associated with positive lymph node status and high histological grade (P<0.01). Abnormality of E-cadherin expression was related to lymph node metastasis and advanced clinical stage (P<0.05). Abnormal beta-catenin expression was directly correlated with abnormal E-cadherin expression (P<0.01). Her2 positivity showed a direct correlation to abnormal beta-catenin expression (P<0.01), and they cooperated in promoting axillary lymph node metastasis in human breast carcinoma (P<0.01).

CONCLUSIONA direct correlation between positive Her2 expression and abnormal beta-catenin expression exists in human breast carcinoma, and positive Her2 expression may have functional interactions with abnormal activation of Wnt/beta-catenin signaling pathway.

Adult ; Aged ; Breast Neoplasms ; metabolism ; pathology ; Cadherins ; metabolism ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Receptor, ErbB-2 ; metabolism ; beta Catenin ; genetics ; metabolism

OBJECTIVETo investigate the expression of Twist, E-cadherin and N-cadherin in breast carcinoma tissue and to analyse their effects on the breast carcinoma differentiation, size, infiltration and metastasis of the breast carcinoma.

METHODSThe expression of Twist, E-cadherin and N-cadherin in 56 cases of breast invasive ductal carcinoma, 38 cases of invasive lobular carcinoma, 41 cases of carcinoma in situ and 10 cases of normal breast tissue was detected using immunohistochemistry.

RESULTS(1) The expression rate of Twist in three types of breast carcinoma was 46.4% (26/56), 79.0% (30/38) and 26.8% (11/41) respectively, and the expression of Twist in invasive lobular carcinoma was significantly higher than that in invasive ductal carcinoma and carcinoma in situ (P = 0.002, P = 0.000). The expression rate of E-cadherin in three types of breast carcinoma was 78.6% (44/56), 29.0% (11/38) and 80.5% (33/41) respectively, and the expression of E-cadherin in invasive ductal carcinoma and carcinoma in situ was significantly higher than that in invasive lobular carcinoma (P = 0.000, P = 0.000). The expression rate of N-cadherin in three types of breast carcinoma was 53.6% (30/56), 68.4% (26/38) and 31.7% (13/41) respectively, and the expression of N-cadherin in invasive ductal carcinoma and invasive lobular carcinoma was significantly higher than that in carcinoma in situ (P = 0.033, P = 0.001). (2) In all the 135 cases, the expression of Twist was not correlated with that of E-cadherin (P = 0.005, Spearman correlation coefficient = -0.239), however, there was a positive correlation between the expression of Twist and N-cadherin and statistically significant(P = 0.000, Spearman correlation coefficient = 0.319). (3) In the invasive ductal carcinoma, the expression of N-cadherin in poorly-differentiated carcinoma was significantly higher than that of the moderately-or well-differentiated ones (P = 0.004). (4) In the invasive lobular carcinoma, the expression of Twist in cases with lymph node metastasis was significantly higher than that of cases without metastasis (P = 0.037).

CONCLUSIONSTwist, E-cadherin and N-cadherin have different expression patterns in the three kinds of breast carcinoma. The positive expression of Twist was correlated to lymph node metastasis in invasive lobular carcinoma and the positive expression of N-cadherin was correlated to cell the tissue differentiation in invasive ductal carcinoma. Detection of the expression of these biomarkers may provide a valuable reference for the study of breast carcinoma progression, metastasis and for the judgment of the biological behavior of the carcinoma.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; metabolism ; pathology ; Cadherins ; metabolism ; Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Lobular ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Twist-Related Protein 1 ; metabolism

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

OBJECTIVETo study the significance of interleukin-1beta (IL-1beta) expression and microvascular density (MVD) in invasive micropapillary carcinoma (IMPC) of breast.

METHODSImmunohistochemical study for IL-1beta and CD34 was performed on 100 cases of IMPC and 97 cases of invasive ductal carcinoma (IDC). The relationship between IL-1beta expression, MVD and various pathologic parameters (estrogen and progesterone receptor status, Ki-67 proliferative index, histologic grade and lymph node metastasis) in IMPC was analyzed.

RESULTSThere was no significant difference in expression of IL-1beta between IMPC and IDC (P = 0.924). The expression of IL-1beta positively correlated with proliferative index (P = 0.023), histologic grade (P = 0.038) and lymph node metastasis (P = 0.008), and negatively correlated with estrogen receptor expression (P = 0.035). The MVD in IMPC was significantly higher than that in IDC (66.4 versus 60.0, P = 0.003). The mean MVD in node-positive IMPC was higher than that in node-negative IMPC (68.8 versus 54.4, P = 0.001). In IMPC, the MVD in histologic grade II and III tumors was much higher than that in histologic grade I tumors (68.3 versus 59.9, P = 0.025). It had no relationship with hormonal receptor status and proliferative index.

CONCLUSIONOverexpression of IL-1beta and high microvessel density may have important roles in tumor cell proliferation and lymph node metastasis in IMPC.

Breast Neoplasms ; metabolism ; pathology ; Carcinoma ; pathology ; Carcinoma, Ductal, Breast ; pathology ; Carcinoma, Papillary ; metabolism ; Female ; Humans ; Interleukin-1beta ; metabolism ; Lymph Nodes ; metabolism ; pathology ; Lymphatic Metastasis ; pathology ; Middle Aged ; Neoplasm Invasiveness ; physiopathology