To evaluate the prognostic significance of bcl-2, we investigated the correlation of bcl-2 expression with the established indicators of prognosis and tumor behavior in breast cancer. This study included a patient group of 91 histologically diagnosed female breast carcinomas. To determine the bcl-2 immunoreactivity, we used a monoclonal antibody directed against the bcl-2 protein by immunohistochemistry from paraffin-embedded tissue in a series of 91 women with breast cancer. Interpretable DNA histograms were obtained from 84 patients. The median age at diagnosis was 45.5 years and the median follow-up time was 30.5 months. Forty-eight (52.7%) cancers showed the bcl-2 immunoreactivity in the cytoplasm. The nonneoplastic portion of ductal epithelial cells and normal lymphocytes were usually stained with bcl-2 antibody. Estrogen receptors (ER)(p < 0.001) and progesterone receptors (PR) (p < 0.001) showed strong positive correlation with bcl-2 immunoreactivity. The histologic grade (p < 0.05) and nuclear grade (p < 0.01) also showed positive relationships with bcl-2 positivity but tumor size (p > 0.05) and DNA ploidy (p > 0.05) were not related with it. The bcl-2 positive patients showed longer survival (p < 0.05) compared to bcl-2 negative tumors in univariate analysis (Kaplan-Meier life table analysis). Using multivariate analysis with Cox regression, bcl-2 (p > 0.05), nuclear grade (p > 0.05), ER status (p > 0.1) and PR status(p > 0.1) were not reliable indicators for overall survival except histologic grade (p < 0.05). Our results suggest that bcl-2 expression may be related to hormonal regulation and tumor differentiation in breast carcinoma. Larger patient study groups with a longer follow-up period will be helpful to clarify the prognostic significance of bcl-2.
Breast Neoplasms/pathology* ; Breast Neoplasms/metabolism* ; Carcinoma in Situ/pathology* ; Carcinoma in Situ/metabolism* ; Carcinoma, Infiltrating Duct/pathology* ; Carcinoma, Infiltrating Duct/metabolism* ; Female ; Human ; Middle Age ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism

Breast Neoplasms ; pathology ; Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; Carcinoma, Papillary ; metabolism ; pathology ; Collagen Type IV ; metabolism ; Female ; Humans ; Neoplasm Invasiveness ; pathology

Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Endometrioid ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo investigate the differential expressions of nucleolin in invasive cervical squamous cell carcinoma, cervical intraepithelial neoplasms (CIN) and normal cervical epithelial tissues and explore the role of nucleolin in the carcinogenesis and progression of cervical squamous cell carcinoma.

METHODSFifty specimens of invasive cervical squamous cell carcinoma, 65 specimens of CIN, and 60 adjacent normal cervical epithelial tissue specimens were examined immunohistochemically for nucleolin expression. The correlation of nucleolin expression levels with histological grades of invasive cervical squamous cell carcinoma and CIN were analyzed.

RESULTSThe specimens of invasive cervical squamous cell carcinoma showed a significantly higher positivity rate for nucleolin expression than CIN and normal cervical epithelial tissues, and the rate in CIN tissues was significantly higher than that in normal cervical epithelial tissues (P<0.01). The expression level of nucleolin was significantly higher in invasive cervical squamous cell carcinoma than in CIN and normal cervical epithelia tissues, and higher in CIN than in normal cervical epithelia tissues, whose immunostaining scores were 7.6±0.3, 6.1±0.2, and 3.0±0.2, respectively (P<0.01). The mean nucleolin immunostaining score was significantly higher in poorly and moderately differentiated than in highly differentiated cervical squamous cell carcinoma (7.9 vs 7.1, P<0.01), and higher in high grade CIN than in low grade CIN tissues (6.0 vs 4.0, P<0.01).

CONCLUSIONSOverexpression of nucleolin plays an important role during carcinogenesis of cervical squamous cell carcinoma and is positively correlated with tumor progression of CIN and cervical squamous cell carcinoma.

Carcinogenesis ; Carcinoma in Situ ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; Disease Progression ; Female ; Humans ; Phosphoproteins ; metabolism ; RNA-Binding Proteins ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology

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

OBJECTIVETo investigate in situ mRNA expression of HER2 oncogene in breast cancers with equivocal immunohistochemical results, and to explore the potential feasibility of RNAscope technique in evaluating HER2 status in breast cancers.

METHODSSixty-nine FFPE samples of invasive ductal breast cancer with equivocal HER2 immunohistochemistry results (IHC 2+) were collected from surgical excisions from Peking Union Medical College Hospital between June 2010 and June 2013. HER2 status and in situ mRNA expression were tested by fluorescence in situ hybridization (FISH) and RNAscope respectively using tissue microarray constructed from tumor paraffin blocks. The results of HER2 mRNA expression were scored 0 to 4 (from low to high levels) according to mRNA expression in 100 cancer cells. HER2 mRNA expression was evaluated in two groups of patients, with positive and negative FISH results.

RESULTSTwenty-three of the 69 samples were FISH positive, including 16 samples that were scored 4 by RNAscope (70%, 16/23), 6 samples were scored 3 (26%, 6/23) and one sample was scored 2 (4%, 1/23). High in situ mRNA expression (score 4 or 3) were observed in 96% of HER2 FISH positive samples. All of samples that were scored 4 by RNAscope were FISH positive. Forty-six samples were FISH negative, including 17 samples that were scored 3 by RNAscope (37%, 17/46), 25 samples were scored 2 (54%, 25/46), and 4 samples were scored 1 (9%, 4/46).

CONCLUSIONSBreast cancer with HER2 IHC 2+ could be further classified according to in situ mRNA expression status. Among them, RNAscope score of 4 could be one of the interpretation criteria for re-testing IHC 2+ samples. In situ detection of HER2 mRNA may be an additional candidate method of confirmation for HER2 gene amplification or protein overexpression, and has potential clinical utility.

Beijing ; Carcinoma, Ductal, Breast ; diagnosis ; metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; RNA, Messenger ; metabolism ; Receptor, ErbB-2 ; 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 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 evaluate the application of the immunohistochemistry (IHC) and the fluorescence in situ hybridization (FISH) in detecting the amplification and the expression of HER-2 gene in the breast cancer patients.

METHODSSixty-six cases of paraffin-embeded breast cancer samples with overexpression, low or no expression of HER-2 gene as detected by IHC were analyzed for HER-2 gene amplification using FISH.

RESULTSAmong the 42 samples with HER-2 gene overexpression (3+/2+) detected by IHC, 31 showed positive HER-2 gene amplification and 11 showed negative HER-2 gene amplification in FISH. In the 24 samples with low or no HER-2 gene expression (1+/-) detected by IHC, no HER-2 gene amplification was detected by FISH. The results of the two testing methods showed a good consistency with the kappa coefficient of 0.672 (P<0.001). We also found that the 17 chromosome polysomy in 42% of the samples and the incidence of 17 polysomy was significantly higher in the HER-2 gene overexpression (3+/2+) group than in low or no HER-2 gene expression (1+/-) group (chi(2)=4.688, P=0.03).

CONCLUSIONIHC can be used as a screening method for detecting HER-2 gene amplification, and FISH should be performed in cases of HER-2 gene overexpression (3+/2+) as detected by IHC.

Breast Neoplasms ; genetics ; metabolism ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Receptor, ErbB-2 ; analysis ; genetics