BACKGROUND: Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and its specific tissue inhibitor - tissue inhibitor of metalloproteinases-1 (TIMP-1) may play an important role in the pathogenesis and spread of cancer. We investigated the plasma levels of M-CSF, MMP-9, and TIMP-1 in comparison with a commonly accepted tumor marker CA 15-3 in breast cancer patients and in control groups. METHODS: The cohort included 110 breast cancer patients in groups at stages I-IV. The control group consisted of 50 healthy volunteers and 50 benign tumor patients. Plasma levels of M-CSF, MMP-9, and TIMP-1 were determined by using ELISA, while CA 15-3 concentrations were determined by using chemiluminescent microparticle immunoassay (CMIA). RESULTS: The results showed significant differences in concentrations of the analyzed parameters and in levels of CA 15-3 between the groups of breast cancer patients and the two control groups. Diagnosis using these markers was equal to that using CA 15-3 in terms of sensitivity, predictive values of positive and negativetest results (PPV, NPV) and area under the ROC curve (AUC) in the studied groups. The diagnostic specificities of MMP-9, TIMP-1, M-CSF, and CA 15-3 showed equally high values (95%). The combined use of all tested parameters with CA 15-3 resulted in increased sensitivity, NPV, and AUC, especially in the combination of M-CSF with tumor markers (76%, 64%, and 0.8653). CONCLUSIONS: These findings suggest the tested parameters are useful in the diagnosis of breast cancer patients (except stage I), when combined with CA 15-3.
Adult ; Aged ; Area Under Curve ; Biomarkers, Tumor/*blood ; Breast Neoplasms/*diagnosis/genetics/pathology ; Case-Control Studies ; Female ; Humans ; Macrophage Colony-Stimulating Factor/*blood ; Matrix Metalloproteinase 9/*blood ; Middle Aged ; Mucin-1/blood ; Neoplasm Staging ; Poland ; ROC Curve ; Sensitivity and Specificity ; Tissue Inhibitor of Metalloproteinase-1/*blood

Pain perception is influenced by multiple factors. The single nucleotide polymorphisms (SNPs) of some genes were found associated with pain perception. This study aimed to examine the association of the genotypes of ABCB1 C3435T, OPRM1 A118G and COMT V108/158M (valine 108/158 methionine) with pain perception in cancer patients. We genotyped 146 cancer pain patients and 139 cancer patients without pain for ABCB1 C3435T (rs1045642), OPRM1 A118G (rs1799971) and COMT V108/158M (rs4680) by the fluorescent dye-terminator cycle sequencing method, and compared the genotype distribution between groups with different pain intensities by chi-square test and pain scores between groups with different genotypes by non-parametric test. The results showed that in these cancer patients, the frequency of variant T allele of ABCB1 C3435T was 40.5%; that of G allele of OPRM1 A118G was 38.5% and that of A allele of COMT V108/158M was 23.3%. No significant difference in the genotype distribution of ABCB1 C3435T (rs1045642) and OPRM1 A118G (rs1799971) was observed between cancer pain group and control group (P=0.364 and 0.578); however, significant difference occurred in the genotype distribution of COMT V108/158M (rs4680) between the two groups (P=0.001). And the difference could not be explained by any other confounding factors. Moreover, we found that the genotypes of COMT V108/158M and ABCB1 C3435T were associated with the intensities of pain in cancer patients. In conclusion, our results indicate that the SNPs of COMT V108/158M and ABCB1 C3435T significantly influence the pain perception in Chinese cancer patients.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Breast Neoplasms ; complications ; diagnosis ; genetics ; pathology ; Catechol O-Methyltransferase ; genetics ; Female ; Gastrointestinal Neoplasms ; complications ; diagnosis ; genetics ; pathology ; Gene Expression ; Gene Frequency ; Genital Neoplasms, Female ; complications ; diagnosis ; genetics ; pathology ; Genital Neoplasms, Male ; complications ; diagnosis ; genetics ; pathology ; Genotype ; Humans ; Lung Neoplasms ; complications ; diagnosis ; genetics ; pathology ; Male ; Middle Aged ; Pain ; complications ; diagnosis ; genetics ; pathology ; Pain Measurement ; Pain Perception ; Polymorphism, Single Nucleotide ; Receptors, Opioid, mu ; genetics

Breast Neoplasms ; diagnosis ; genetics ; pathology ; Carcinoma, Ductal, Breast ; diagnosis ; genetics ; pathology ; Centromere ; genetics ; Chromosomes, Human, Pair 17 ; genetics ; Early Detection of Cancer ; methods ; Female ; Gene Amplification ; Gene Dosage ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization ; standards ; Receptor, ErbB-2 ; genetics

BACKGROUND: Therapy-related myeloid neoplasms (t-MN) occur as late complications of cytotoxic therapy. This study reviewed clinical and cytogenetic characteristics of patients with t-MN at a single institution in Korea. METHODS: The study subjects included 39 consecutive patients diagnosed with t-MN. Each subject's clinical history of previous diseases, treatments, and laboratory data was reviewed, including cytogenetics. The primary diagnosis was hematologic malignancy in 14 patients and solid tumor in 25 patients. RESULTS: Therapy-related acute myeloid leukemia (t-AML, 66.7%) was found to be more common than therapy-related myelodysplastic syndrome (t-MDS). Primary hematologic malignancies that were commonly implicated included mature B-cell neoplasm and acute leukemia. Breast cancer was the most common primary solid tumor. The mean time interval from cytotoxic therapy initiation to t-MN detection was 49 months. Chromosomal aberrations were observed in 35 patients, and loss of chromosome 5, 7, or both accounted for 41% of all cases. Balanced rearrangements occurred in 13 patients; these patients showed shorter latency intervals (mean, 38 months) than patients with loss of chromosome 5 or 7 (mean, 61 months). CONCLUSIONS: In this study, we determined the clinical and cytogenetic characteristics of Korean patients with t-MN. Although our results were generally consistent with those of previous reports, we found that t-MN resulting from de novo leukemia was common and that t-AML was more common than t-MDS at presentation. Multi-institutional studies involving a larger number of patients and additional parameters are required to investigate the epidemiology, genetic predisposition, and survival rate of t-MN in Korea.
Adolescent ; Adult ; Aged ; Antineoplastic Agents/*adverse effects/therapeutic use ; Asian Continental Ancestry Group ; Bone Marrow/pathology ; Breast Neoplasms/drug therapy/pathology/radiotherapy ; Child ; Child, Preschool ; Chromosome Aberrations ; Chromosomes, Human, Pair 5 ; Chromosomes, Human, Pair 7 ; Female ; Hematologic Neoplasms/drug therapy/pathology/radiotherapy ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute/*diagnosis/etiology/genetics ; Male ; Middle Aged ; Myelodysplastic Syndromes/*diagnosis/etiology/genetics ; Neoplasms, Second Primary/*diagnosis/etiology/genetics ; Republic of Korea ; Young Adult

To verify the reliability of targeted detecting HER2 positive cancer cells and clinical pathological tissue specimens with a recombinant anti HER2 single chain antibody in single chain Fv fragment (scFv) format, we have constructed the fusion variable regions of the ScFv specific for HER2/neu. labeled a green-fluorescent protein(GFP). The humanized recombinant Anti HER2 ScFv-GFP gene was inserted into pFast Bac HT A, and expressed in insect cells sf9. Then the recombinant fusion protein Anti HER2 ScFv-GFP was properly purified with Ni2+-NTA affinity chromatography from the infected sf9 cells used to test the specificity of the fusion antibody for HER2 positive cancer cells. Firstly, the purified antibody incubated with HER2 positive breast cancer cells SKBR3, BT474 and HER2 negative breast cancer cells MCF7 for 12 h/24 h/48 h at 37 degrees C, in order to confirm targeted detecting HER2 positive breast cancer cells by Laser Confocal Microscopy. Furthermore, the same clinical pathological tissue samples were assessed by immunohistochemistry (IHC) and the fusion antibody Anti HER2 ScFv-GFP in the meanwhile. The data obtained indicated that the recombinant eukaryotic expression plasmid pFast Bac HT A/Anti HER2 ScFv-GFP was constructed successfully In addition, obvious green fluorescent was observed in insect cells sf9. When the purified fusion antibody was incubated with different cancer cells, much more green fluorescent was observed on the surface of the HER2 positive cancer cells SKBR3 and BT474. In contrast, no green fluorescent on the surface of the HER2 negative cancer cells MCF7 was detected. The concentration of the purified fusion antibody was 115.5 microg/mL, of which protein relative molecular weight was 60 kDa. The analysis showed the purity was about 97% and the titer was about 1:64. The detection results of IHC and fusion antibody testing indicated the conformity. In summary, the study showed that the new fusion antibody Anti HER2 ScFv-GFP can test HER2 positive cancer cells, indicating a potential candidate method for clinical HER2 positive specimens detection.
Animals ; Breast Neoplasms ; diagnosis ; pathology ; Female ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; Humans ; MCF-7 Cells ; Receptor, ErbB-2 ; analysis ; Recombinant Fusion Proteins ; genetics ; Sf9 Cells ; Single-Chain Antibodies ; genetics

Breast cancer is the most common cancer in women worldwide. It is necessary to identify biomarkers for early detection, to make accurate prognoses, and to monitor for any recurrence of the cancer. In order to identify potential breast cancer biomarkers, we analyzed the plasma samples of women diagnosed with breast cancer and age-matched normal healthy women by mTRAQ-based stable isotope-labeling mass spectrometry. We identified and quantified 204 proteins including thrombospondin-1 (THBS1) and bromodomain and WD repeat-containing protein 3 (BRWD3) which were increased by more than 5-fold in breast cancer plasma. The plasma levels of the two proteins were evaluated by Western blot assay to confirm for their diagnostic value as serum markers. A 1.8-fold increase in BRWD3 was observed while comparing the plasma levels of breast cancer patients (n = 54) with age-matched normal healthy controls (n = 30), and the area under the receiver operating characteristic curve (AUC) was 0.917. THBS1 was detected in pooled breast cancer plasma at the ratio similar to mTRAQ ratio (> 5-fold). The AUC value for THBS1 was 0.875. The increase of THBS1 was more prominent in estrogen receptor negative and progesterone receptor negative patients than receptor-positive patients. Our results are evidence of the diagnostic value of THBS1 in detecting breast cancer. Based on our findings, we suggest a proteomic method for protein identification and quantification lead to effective biomarker discovery.
Adult ; Breast Neoplasms/*diagnosis/genetics/pathology ; Early Detection of Cancer ; Female ; Gene Expression Profiling ; Humans ; Middle Aged ; Pathology, Molecular/methods ; Predictive Value of Tests ; Prognosis ; *Proteomics ; Thrombospondin 1/*blood ; Transcription Factors/*blood ; Tumor Markers, Biological/*blood

Clinicopathological characteristics and prognostic factors of mucinous carcinoma (MC) were compared with invasive ductal carcinoma-not otherwise specified (IDC-NOS). Clinicopathological characteristics and survivals of 104 MC patients were retrospectively reviewed and compared with those of 3,936 IDC-NOS. The median age at diagnosis was 45 yr in MC and 47 yr in IDC-NOS, respectively. The sensitivity of mammography and sonography for pure MC were 76.5% and 94.7%, respectively. MC showed favorable characteristics including less involvement of lymph node, lower stage, more expression of estrogen receptors, less HER-2 overexpression and differentiated grade, and better 10-yr disease-free survival (DFS) and overall survival (OS) (86.1% and 86.3%, respectively) than IDC-NOS (74.7% and 74.9%, respectively). Ten-year DFS of pure and mixed type was 90.2% and 68.8%, respectively. Nodal status and stage were statistically significant factors for survival. MC in Koreans showed similar features to Western populations except for a younger age of onset than in IDC-NOS. Since only pure MC showed better prognosis than IDC-NOS, it is important to differentiate mixed MC from pure MC. Middle-aged Korean women presenting breast symptoms should be examined carefully and evaluated with an appropriate diagnostic work-up because some patients present radiologically benign-like lesions.
Adenocarcinoma, Mucinous/diagnosis/genetics/*pathology ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/classification/diagnosis/genetics/*pathology ; Carcinoma, Ductal/diagnosis/genetics/*pathology ; Disease-Free Survival ; Female ; Genes, erbB-2 ; Humans ; Korea ; Lymphatic Metastasis ; Mammography ; Middle Aged ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; Survival Rate ; Young Adult

To evaluate the relationship between p27Kip1 low expression in breast cancer and its prognostic implication in breast carcinoma patients. Methods All data that were associated with the study of the relationship between p27Kip1 and the prognosis for breast cancer was pooled from Cochrane library, PubMed, Embase and Medlinebase. The outcome was measured using the risk ratio (RR). Data pooling was performed by RevMan 4. 2. Results 6457 patients from 20 studies were included in this meta-analysis. RR estimate of overall survival (OS) for patients with low level p27Kip1 was 2.07 [1.66,2.60] (P<0.01). For disease free survival (DFS), the pooled RR was 1.27 [1.10,1.47] (P<0.05). The combined RR estimate of relapse free survival (RFS) for patients with low level of p27Kip1 was 1.49 [0.92, 2.42] (P >0.05). In patients with lymph node negative breast carcinoma, the combined RR for OS and RFS were 1.98 [1.34,2.91] (P <0.01) and 1.28 [0.45,3.65] (P > 0.05), respectively. Among the patients with lymph node positive breast carcinoma, the combined RR for OS and RFS was 1.92 [1.31, 2.82] (P=0.0009) and 1.35 [0.96,1.89] (P>0.05) respectively. Conclusions Low level of p27Kip1 appears to be an independent prognostic factor to OS and DFS of breast cancer patients but not to RFS. Additional studies with large patient number and widely accepted practical methods are required to derive the precise prognostic significance of p27Kip1 expression in breast cancer patients.
Biomarkers, Tumor ; analysis ; Breast Neoplasms ; diagnosis ; genetics ; metabolism ; pathology ; Carcinoma ; diagnosis ; genetics ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; genetics ; metabolism ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Lymphatic Metastasis ; diagnosis ; physiopathology ; Neoplasm Staging ; methods ; Prognosis

OBJECTIVETo summarize the morphological features of basal-like subtype of invasive breast carcinoma (BLSIBC), and to look for diagnostic clues for its recognition.

METHODSImmunohistochemistry was performed in 109 cases of invasive ductal carcinoma, with CK5/6, CK14, CK8/ 18, 34betaE12, calponin, p63, CD10, ER, PR and c-erbB-2 monoclonal antibodies. Five subtypes were classified according to immunophenotypes: luminal A subtype (ER+/HER2-), luminal B subtype (ER+/ HER2+), normal breast-like subtype (ER/HER2-), HER2-overexpressing subtype and BLSIBC which was identified with at least one kind of basal-like cytokeratins or markers of myoepithelium and ER/HER2. The microscopic features of basal-like subtype were also analyzed.

RESULTSThe number of luminal A case was 48 (44.0%), luminal B 15 (13.8%), HER2 over-expressing 15 (13.6%), normal breast-like 10 (9.1%), basal-like subtype 19 (17.4%). Besides, the other two cases expressed c-erbB-2 or/and ER plus markers for myoepithelium, thus were excluded from all the five mentioned subtypes. Of the 19 basal-like subtype, CK5/6 was expressed in 16 cases, CK8/18 in 17 cases, CK14 in 11 cases, 34betaE12 in 18 cases, p63 in 5 cases, CD10 in 6 cases, and calponin in 1 case. The diameter of the BLSIBC cases was 1.2-7 cm (averagely 3.9 cm) , and in 6 cases, the tumor diameter was >5 cm. Only one case displayed extensive in situ component, 9 cases were grade 2, and 9 cases were grade 3. Compared to non basal subtype, there were significantly more high grade cases (P <0.01). The morphological features of basal-like subtype were summarized as the followings: pushing margin (13 cases), lymphocytic tissue hyperplasia (18 cases), nest or sheet arrangement (18 cases), nucleus grade 3 and scattered giant or bizarre nuclei (17 cases), syncytial growth (7 cases), and comedo-like necrosis (17 cases). The frequency of these features were significantly more common than non basal subtype (P <0.01).

CONCLUSIONThe morphologic diagnostic features of BLSIBC are pushing margins, lymphocyte infiltration, comedo-like necrosis, gigantic cell and syncytial growth.

Biomarkers, Tumor ; analysis ; Breast Neoplasms ; diagnosis ; pathology ; Carcinoma, Basal Cell ; pathology ; Female ; Genes, erbB-2 ; physiology ; Humans ; Immunohistochemistry ; Keratin-5 ; analysis ; Magnetic Resonance Imaging ; Male ; Mammography ; instrumentation ; methods ; Neoplasm Invasiveness ; physiopathology ; Prognosis ; Receptor, Epidermal Growth Factor ; genetics ; Receptor, ErbB-2 ; analysis ; genetics ; Receptors, Estrogen ; analysis ; Receptors, Progesterone ; analysis ; Ultrasonography ; methods

Breast Neoplasms ; diagnosis ; genetics ; pathology ; Clinical Laboratory Techniques ; adverse effects ; trends ; Diagnostic Errors ; Female ; Genes, BRCA2 ; physiology ; Humans