PURPOSE: The aims of this study were to compare the expression of sarcosine metabolism-related proteins between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and to determine the implications of these results. MATERIALS AND METHODS: Tissue microarrays were constructed, containing 30 samples from normal breast tissue, 114 samples from patients with ILC, and 692 samples from patients with IDC. Immunohistochemical staining was performed to examine the expression of sarcosine metabolism-related proteins [glycine N-methyltransferase, sarcosine dehydrogenase, and l-pipecolic acid oxidase (PIPOX)]. RESULTS: The sarcosine metabolic phenotype differed between ILC and IDC (p<0.001). In IDC, sarcosine metabolic phenotype was distributed as null type (61.7%)>low sarcosine type (30.4%)>high sarcosine type (5.0%)>intermediate type (2.9%). However, in ILC, the sarcosine metabolic phenotype was distributed as low sarcosine type (61.4%)>null type (32.5%)>intermediate type (5.3%)>high sarcosine type (0.9%). PIPOX showed higher expression in ILC than in IDC (p<0.001) and correlated with androgen receptor (AR) positivity (p=0.001) in ILC. CONCLUSION: Expression of sarcosine metabolism-related proteins differed between ILC and IDC. Low sarcosine type was the majority sarcosine metabolic phenotype of ILC. PIPOX expression was predominant in ILC and correlated with AR positivity.
Adult ; Breast/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/*metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Phenotype ; Proportional Hazards Models ; Regression Analysis ; Retrospective Studies ; Sarcosine/genetics/*metabolism ; Tissue Array Analysis

OBJECTIVETo investigate the clinicopathologic features, clinical progress and prognosis of the basal-like subtype of invasive lobular carcinoma (ILC) of the breast.

METHODSFour cases of ILC were analyzed by detailed histopathologic observation and immunohistochemical staining for E-cadherin, p120 catenin, ER, PR, HER2, CK5/6, EGFR, p63, p53, Ki-67 using MaxVision method. The follow-up and clinical data were analyzed.

RESULTSMorphologically, one case was mixed ILC and three cases were pleomorphic ILC. The tumor cells were negative for E-cadherin except one case with focal membrane positivity, and all showed p120 catenin cytoplasmic positivity except one case with focal membrane positivity. All cases were negative for ER, PR and HER2 (triple negative), and positive for EGFR and CK5/6. Two cases were positive for p63. The cases were partly and weakly positive for p53, and the Ki-67 positive rate was between 30% and 75%. Follow-up data showed that two cases developed chest wall metastases, and in one case, there was progression to liver and abdominal metastases.

CONCLUSIONSILC of the breast are ER, PR and HER2 "triple negative", CK5/6 and EGFR positive, indicative of basal-like characteristics. Basal-like subtype of ILC are peculiarly prone to metastasis and poor response to chemotherapy, suggesting that it is associated with poor prognosis.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Cadherins ; metabolism ; Carcinoma, Lobular ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Catenins ; metabolism ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Ki-67 Antigen ; metabolism ; Liver Neoplasms ; secondary ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Thoracic Neoplasms ; secondary ; Thoracic Wall ; Tumor Suppressor Protein p53 ; metabolism

Adult ; Breast Neoplasms ; metabolism ; pathology ; secondary ; Carcinoid Tumor ; metabolism ; pathology ; surgery ; Carcinoma, Adenoid Cystic ; pathology ; Carcinoma, Lobular ; metabolism ; pathology ; secondary ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; surgery ; Chromogranin A ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Hysterectomy ; Keratins ; metabolism ; Neoplasms, Multiple Primary ; metabolism ; pathology ; surgery ; Ovarian Neoplasms ; metabolism ; pathology ; Sex Cord-Gonadal Stromal Tumors ; metabolism ; pathology ; Synaptophysin ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; surgery

Adenocarcinoma, Mucinous ; drug therapy ; metabolism ; pathology ; surgery ; Adult ; Aged ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Lobular ; drug therapy ; metabolism ; pathology ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; MCF-7 Cells ; metabolism ; Mastectomy, Modified Radical ; Membrane Proteins ; metabolism ; Middle Aged ; Receptor, ErbB-2 ; metabolism ; Sphingosine N-Acyltransferase ; metabolism ; Survival Rate ; Tumor Suppressor Proteins ; metabolism

OBJECTIVETo study the clinical and morphological features as well as immunophenotype of tubulolobular carcinoma of the breast (TLC).

METHODSEight cases of TLC were retrieved from 97 cases of invasive lobular carcinoma between January 2005 and March 2010 in the Peking Union Medical College Hospital. The clinical features and pathologic findings were studied and immunohistochemistry was performed for the expression of ER, PR, HER2, p53, E-cadherin, CK34βE12 and CK8.

RESULTSAmong the breast cancer patients, the incidence of TLC was about 1.0% (8/880). The mean age of the patients was 59 years, with a range of 45 to 79 years. All patients were asymptomatic, with incidental finding of a mass in the breast on health examination. Common findings on sonography included a hypoechoic nodule with irregular shape and spiculated margin. Histologically, the small uniform tumor cells were arranged in a mixed pattern showing single cells, single-cell files or cords, small round to angulated tubules, and infiltrating lobular or targetoid patterns around ducts that were specific for classical invasive lobular carcinoma. Low or intermediate grade intraepithelial neoplasms which had similar cellular morphology with the invasive tumor often appeared in the periphery, including ductal carcinoma in situ, lobular carcinoma in situ and intraductal papillary carcinoma. Immunohistochemistry of the tumor cells showed intense reactivity to ER (7/8) and PR (8/8), but no reactivity to HER2 or p53. Both the tubules and single-cell file or cords expressed E-cadherin (7/8), CK34βE12 (5/8), and CK8 (8/8) with a uniform staining pattern. All patients underwent modified radical mastectomy and 2/8 patients had metastatic carcinoma in the axillary lymph nodes. Seven patients were followed up for 28 to 75 months and remained well, including one patient that had a new breast mass 60 months after surgery, but had no treatment up to now.

CONCLUSIONSTLC is a rare variant of invasive breast cancer and reveals mixed histologic features of both tubular and lobular carcinoma with common expression of E-cadherin, CK8 and CK34βE12. A better understanding of TLC would enable pathological diagnosis to be made reasonably and accurately.

Aged ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Cadherins ; metabolism ; Carcinoma in Situ ; metabolism ; pathology ; surgery ; Carcinoma, Lobular ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Keratin-8 ; metabolism ; Keratins ; metabolism ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Treatment Outcome

OBJECTIVETo study the changes of expression of Survivin mRNA, BCRP mRNA and HER-2 mRNA in breast cancer after TE regimen neoadjuvant chemotherapy, and to find biological markers to predict the efficiency of TE regimen neoadjuvant chemotherapy.

METHODSThe gene expressions were detected by RT-PCR from 56 breast cancer patients before and after TE regimen neoadjuvant chemotherapy (docetaxel and epirubicin). The relationships between these gene expressions and chemotherapy responses were analyzed.

RESULTSThe overall response rate to neoadjuvant chemotherapy was 71.4%, including 8.9% (5/56) with complete response and 62.5% (35/56) with partial response. Pathological complete response was found in 4 cases (7.1%). Stable disease and progression of disease were 23.2% (13/56) and 5.4% (3/56), respectively. The expression of Survivin mRNA after neoadjuvant chemotherapy was 35.7% (20/56), significantly lower than 60.7% (34/56) before neoadjuvant chemotherapy (P = 0.008). The expression of BCRP mRNA after neoadjuvant chemotherapy was 19.6%, significantly lower than 37.5% before neoadjuvant chemotherapy (P = 0.036). The positive rate of HER-2 mRNA expression was 41.1% before the chemotherapy, and reduced to 21.4% after the chemotherapy (P = 0.025). The effective rates of the single positive expression of Survivin mRNA or BCRP mRNA were both lower than that of negative expression (P < 0.05). The level of HER-2 mRNA expression alone was not significantly associated with the effective rate of chemotherapy (P = 0.144). When the expression of all Survivin mRNA, BCRP mRNA and HER-2 mRNA were negative, the effective rate of neoadjuvant chemotherapy was higher than that in patients with positive expression (P = 0.003). The level of Survivin mRNA expression was not significantly associated with BCRP mRNA and HER-2 mRNA (P > 0.05).

CONCLUSIONThe expression of Survivin in combination with BCRP and HER-2 is associated with clinical response to TE neoadjuvant chemotherapy in breast cancer, and can be used as predictive biomarkers for chemosensitivity of TE regimen neoadjuvant chemotherapy for breast cancer.

ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; genetics ; metabolism ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; surgery ; Carcinoma, Lobular ; drug therapy ; metabolism ; surgery ; Disease Progression ; Epirubicin ; administration & dosage ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; metabolism ; Mastectomy, Radical ; methods ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Proteins ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Receptor, ErbB-2 ; genetics ; metabolism ; Remission Induction ; Taxoids ; administration & dosage

OBJECTIVETo investigate the effect of Syk on the VEGF-C expression in breast cancer.

METHODSImmunohistochemical EnVision method was used to detect the protein expression of Syk, NFκB and VEGF-C in breast carcinoma; and the relationship between protein expression of Syk, NFκB, VEGF-C and lymph node metastasis was analysed. MDA-MB-231 cells were transfected with pcDNA3.1(-)-Syk, and the effect of Syk gene on the VEGF-C and NFκB expression was determined.

RESULTSIn the lymph node metastatic group, a lower expression rate of Syk and higher expression rate of VEGF-C and NFκB were detected as compared to the non-metastatic group. The expression of Syk was negatively associated with NFκB (r = -0.448, P = 0.002) and VEGF-C (r = -0.620, P = 0.000) expression, and VEGF-C was associated with the nuclear expression of NFκB (r = 0.310, P = 0.036). Compared with the non-transfected cells, the pcDNA3.1(-)-Syk transfected MDA-MB-231 cells showed significantly lower transcriptional level of VEGF-C mRNA, expression level of VEGF-C protein and NFκB activity (P < 0.05).

CONCLUSIONSSyk may play an important role in the lymph node metastasis of breast cancer. It may down-regulate the expression of VEGF-C by inhibiting the activity of NFκB, which thus suppresses lymph node metastasis of breast cancer.

Adult ; Aged ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Carcinoma, Lobular ; genetics ; metabolism ; pathology ; Carcinoma, Medullary ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Female ; Genetic Vectors ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; physiology ; Lymphatic Metastasis ; Middle Aged ; NF-kappa B ; metabolism ; Plasmids ; Protein-Tyrosine Kinases ; genetics ; metabolism ; physiology ; RNA, Messenger ; metabolism ; Syk Kinase ; Transfection ; Vascular Endothelial Growth Factor C ; genetics ; metabolism

OBJECTIVETo investigate expressions of E-cadherin (E-cad), p120catenin (p120), 34βE12 in invasive lobular carcinomas of the breast and their roles of diagnoses.

METHODSThe 81 cases of ILC, including 67 cases of pure type and 14 cases of ductal-lobular mixed type, which had been diagnosed in our department were collected and immunohistochemistry of E-cad, p120 and 34βE12 were performed. All the cases were diagnosed again according to morphology and immunophenotypes (MaxVision method), and difference of diagnoses and expressions of the three indexes were analysed.

RESULTSSixty four of 81 cases were permantly diagnosed of ILC. In the 61 cases of pure type, 54 cases displayed E-cad negative and p120 cytoplastic positive, 1 case displayed E-cad negative and p120 atypical positive, 3 cases displayed E-cad membrane positive and p120 cytoplastic positive, and 3 cases displayed both atypical positive. Fifty two of 61 cases displayed 34βE12 positive. The 3 cases of mixed type displayed p120 cytoplastic positive, and 2 cases displayed E-cad negative and 1 case displayed atypical positive. All the 3 cases displayed 34βE12 positive.

CONCLUSIONSThe diagnosis of ILC is one of the most difficult problems in breast pathology, and combination of E-cad and p120 immunostaining is an effective method for assistance. It needs further studies for invasive ductal carcinomas with morphological features of lobular carcinomas.

Adult ; Aged ; Breast Neoplasms ; diagnosis ; metabolism ; pathology ; Cadherins ; metabolism ; Carcinoma, Ductal, Breast ; diagnosis ; metabolism ; pathology ; Carcinoma, Lobular ; diagnosis ; metabolism ; pathology ; Catenins ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Keratins ; metabolism ; Middle Aged ; Retrospective Studies

PURPOSE: Our study is performed to find out clinicopathlogic and immunohistochemical (IHC) characteristics of triple negative invasive lobular carcinoma (ILC), as has been demonstrated in their invasive ductal counterparts. MATERIALS AND METHODS: Retrospective analysis of variable clinicopathlogic parameters and IHC stains for androgen receptor, estrogen receptor, progesterone receptor, p53, c-kit, galectin-3, cytokeratin 5 (CK5), CK5/6, vimentin, E-cadherin, epidermal growth factor receptor, and HER2 were performed in 117 cases of ILC. RESULTS: Eight cases (6.8%) were triple negative carcinoma (TNC), which showed higher incidence of high histologic grade than non-TNC (p = 0.019). Galectin-3 was expressed with higher incidence in tumor cells of TNC (62.5%) than those of non-TNC (7.3%) (p = 0.000). In contrast, galectin-3 was expressed with higher incidence in stromal cells of non-TNC (53.2%) than those of TNC (12.5%) (p = 0.029). CK5 and CK5/6 were not expressed in all ILCs. CONCLUSION: TNC in ILC showed distinct clinicopathologic and IHC characteristics such as higher histologic grade and increased expression of galectin-3, compared to non-TNC in ILC. TNC in ILC was less frequent and did not show CK5 and CK5/6 expression when compared to TNC in invasive ductal carcinoma.
Adult ; Breast Neoplasms/*metabolism ; Cadherins/metabolism ; Carcinoma, Lobular/*metabolism ; Female ; Galectin 3/metabolism ; Humans ; Immunohistochemistry/*methods ; Keratin-5/metabolism ; Keratin-6/metabolism ; Middle Aged ; Proto-Oncogene Proteins c-kit/metabolism ; Receptor, Epidermal Growth Factor/metabolism ; Receptors, Androgen ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Vimentin/metabolism

OBJECTIVEThe phosphatidylinositol-3-kinase (PI3K)-AKT signaling pathway is considered to play an important role in tumorigenesis. Frequent somatic mutations in the PI3K subunit p110a (PIK3CA) occur in a variety of cancer types. The purpose of this study was to determine the relationship between PIK3CA mutation in breast cancer and pathological features and outcome of patients.

METHODSThe PIK3CA mutations in exons 7, 9, 20 were screened in 250 primary breast cancers using PCR and fluorescent (F)-SSCP, and the results were analyzed according to their cliniopathological data.

RESULTSThe frequency of PIK3CA mutations among the 250 cases was 35.2% (88/250), point mutations in exon 7 were found in 8 (3.2%) cases,40 (16.0%) cases in exon 9 and 47 (18.8%) cases in exon 20. No significant correlation between PIK3CA mutation and age, histological type, differentiation, and lymph node metastasis was observed. Mutations were associated with larger tumor size (P = 0.004) and positive estrogen receptor status (P = 0.008). Patients with PIK3CA mutations showed a significantly worse survival (P = 0.004), particularly in those with positive estrogen receptor expression or non-amplified HER-2 (both P = 0.002).

CONCLUSIONSPIK3CA mutations may play an important role in the carcinogenesis and development of breast cancer. The association with large tumor size, ER+ and poor survival indicates that PIK3CA mutation could be an independent factor for tumor malignant phenotype and prognosis.

Adenocarcinoma ; genetics ; metabolism ; pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Carcinoma, Lobular ; genetics ; metabolism ; pathology ; Carcinoma, Medullary ; genetics ; metabolism ; pathology ; Class I Phosphatidylinositol 3-Kinases ; Exons ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Point Mutation ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Survival Rate ; Tumor Burden ; Young Adult