Adolescent ; Adult ; Brain Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Male ; Meningeal Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Meningioma ; diagnosis ; metabolism ; pathology ; surgery ; Middle Aged ; Mucin-1 ; metabolism ; Neoplasm Recurrence, Local ; Reoperation ; Retrospective Studies ; Tomography, X-Ray Computed ; Vimentin ; metabolism ; Young Adult

OBJECTIVETo establish experimental models for tumor neovascularization and to apply quantitative digital imaging analysis in the study.

METHODSAn endothelial tube formation model was established by human umbilical vein endothelial cells (HUVECs). A vasculogenic mimicry model was established by SGC-7901 gastric cancer cell line. Fertilized eggs were used to establish a chorioallantoic membrane angiogenesis model. Using gene transfection experiment, IRX1 tumor suppressor gene was chosen as a therapeutic target. Image Pro Plus (IPP) analysis software was used for digital vascular images analysis with parameters including points, lines, angles and integral absorbance (IA) for the tubular formation or vasculogenic mimicry.

RESULTSDigital image analysis by IPP showed that HUVEC tubular formation was significantly inhibited in IRX1 transfectant, compared with controls. The tubular numbers in three groups were 12.80 +/- 3.83, 29.00 +/- 5.34 and 28.20 +/- 4.32 (P<0.01). The connection points of tubules in three groups were 13.20 +/- 2.59, 25.00 +/- 2.24 and 24.60 +/- 3.21 (P<0.01). The tubular lengths of three groups were (821.5 +/- 12.5), (930.9 +/- 13.5) and (948.4 +/- 18.1) microm (P=0.022). The IA values of PAS stain in three groups were 3606 +/- 363, 14 200 +/- 1251 and 15 043 +/- 1220 (P<0.01). In chick chorioallantoic membrane model, the angular numbers of tubules in three groups were 6.41 +/- 2.60, 10.27 +/- 2.65 and 9.18 +/- 1.99 (P<0.01).

CONCLUSIONSThe endothelial tube formation model, vasculogenic mimicry model and chorioallantoic membrane angiogenesis model are useful for gene therapy and drug screening with targeting neoplastic vascularization. Professional image analysis software may greatly facilitate the quantitative analysis of tumor neovascularization.

Animals ; Cell Line, Tumor ; Cells, Cultured ; Chorioallantoic Membrane ; blood supply ; Diagnostic Imaging ; methods ; Homeodomain Proteins ; genetics ; metabolism ; physiology ; Human Umbilical Vein Endothelial Cells ; Humans ; Neovascularization, Pathologic ; Neovascularization, Physiologic ; Software ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Transcription Factors ; genetics ; metabolism ; physiology ; Transfection

OBJECTIVETo study the clinicopathologic features, immunophenotypes and differential diagnoses of invasive carcinoma arising in breast microglandular adenosis (MGACA).

METHODSClinical and pathologic findings of 3 cases of MGACA were analyzed by histomorphology and immunohistochemical staining of CK7, S-100 protein, ER, PR, HER2, SMA, MSA, p63 and PAS. Literatures were reviewed.

RESULTS(1) Histologically, 3 tumors all showed a spectrum of glandular proliferations ranging from microglandular adenosis (MGA) to atypical microglandular adenosis (AMGA) to in situ carcinoma (DCIS) to invasive carcinoma. The invasive carcinoma component was ductal in case 1, and matrix-producing in case 2 and case 3. (2) All epithelial cells in MGA, AMGA, DCIS and MGACA were positive for CK7 and S-100 protein, but were negative for ER and HER2. PR was negative in case 1 and case 2 but was low positive in case 3. Myoepithelial cell differentiation was not demonstrated in MGA, AMGA, DCIS and MGACA by immunohistochemical staining for SMA, MSA or p63. PAS staining showed the presence of basement membrane in MGA, AMGA and DCIS, except MGACA.

CONCLUSIONSMGACA is an extremely rare tumor of the breast and has distinct morphological and immunohistochemical features. Further studies are needed to evaluate the clinical behavior of this rare neoplasm.

Adult ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Intraductal, Noninfiltrating ; drug therapy ; metabolism ; pathology ; surgery ; Cell Transformation, Neoplastic ; Diagnosis, Differential ; Disease Progression ; Female ; Fibrocystic Breast Disease ; drug therapy ; metabolism ; pathology ; surgery ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Keratin-7 ; metabolism ; Mastectomy, Modified Radical ; Middle Aged ; Precancerous Conditions ; drug therapy ; metabolism ; pathology ; surgery ; Receptors, Progesterone ; metabolism ; S100 Proteins ; metabolism

OBJECTIVETo investigate the relationship between the pathologic responses and histologic type, grade, the expression of ER, PR and HER2 and their changes in breast carcinoma before and after neoadjuvant chemotherapy (NAC).

METHODSTwo-hundred and nine cases of breast cancer with NAC were analyzed and clinical, pathologic data were evaluated based on the Miller and Payne ( MP) grading system. The expression of ER, PR and HER2 in the cancers before and after NAC were detected by immunohistochemistry (MaxVision method). SPSS 15.0 software was used to conduct statistical analysis.

RESULTS(1) Pathologic responses to the NAC were graded as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases); (2) The expression of ER in core needle biopsy had related negatively to the pathologic response (chi2 = 33.083, P = 0.001). However, the histologic type, grade, ER and PR status, and HER2 expression in surgically-removed specimens had not related to the pathologic response (P>0.05); (3) After NAC, the pathologic type and grade changed in 6. 8% (9/132) and 34.9% (30/86) of the cases, and the rates of changes in the expression of ER, PR and HER2 were 42.4% (75/177), 55.4% (98/177) and 26.6% (46/173) , respectively. Only the expression of HER2 had significant difference between before and after neoadjuvant chemotherapy (P = 0.049). The changes in other data had no relationship with the pathologic response (P>0.05).

CONCLUSIONSAnalysis of core needle biopsy can provide important information to predict the pathologic responses to the NAC. The pathologic appearance, grade, ER, PR and HER2 in breast carcinoma may change after NAC. It is necessary to examine the histologic type, grade and the expression of ER, PR and HER2 after NAC once more.

Adenocarcinoma, Mucinous ; drug therapy ; metabolism ; pathology ; surgery ; Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Lobular ; drug therapy ; metabolism ; pathology ; surgery ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo study the immunophenotype and gene rearrangement pattern of pulmonary lymphomatoid granulomatosis.

METHODSNine cases of pulmonary lymphomatoid granulomatosis, included 5 cases of open lung biopsy, 3 cases of lobectomy specimen and 1 case of autopsy, were retrospectively analyzed by immunohistochemistry, in-situ hybridization for Epstein-Barr virus-encoded RNA, immunoglobulin and T-cell receptor gene rearrangement studies.

RESULTSThe age of patients ranged from 3 to 59 years. The male-to-female ratio was 3: 6. Histologically, all cases showed lymphocytic infiltration surrounding the blood vessels and in the perivascular areas. Most of these lymphoid cells expressed T-cell marker CD3. There were also variable numbers of CD20-positive B cells. The staining for CD56 was negative. According to the WHO classification, there were 4 cases of grade I , 1 case of grade II and 4 cases of grade III lesions. Six cases had gene rearrangement studies performed and 3 of them demonstrated clonal immunoglobulin gene rearrangement (including 1 of the grade II and 2 of the grade III lesions). No T-cell receptor gene rearrangement was detected.

CONCLUSIONSPulmonary lymphomatoid granulomatosis may represent a heterogeneous group of lymphoproliferative disorders. Some of the cases show B-cell immunophenotype and clonal immunoglobulin gene rearrangement, especially the grade II and grade lesions. They are likely of lymphomatous nature.

Adult ; Antigens, CD20 ; metabolism ; CD3 Complex ; metabolism ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Humans ; Immunohistochemistry ; Lung Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Lymphomatoid Granulomatosis ; genetics ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Grading ; Pneumonectomy ; methods ; Retrospective Studies ; Young Adult

OBJECTIVESTo investigate the relationship between the expression of miR-218 and CDK6 in glioma cells, and their biological impacts on the tumor cell proliferation and apoptosis.

METHODSExpression levels of miR-218 as well as CDK6 and Ki-67 proteins were analyzed in 60 cases of gliomas with various grades and 10 control brain tissue samples by tissue microarray, locked oligonucleotide probe in situ hybridization and immunohistochemistry. Glioblastoma multiform cell line (U87MG) was transfected with miR-218 mimics (mimics group) and a control sequence (control group), followed by qRT-PCR detection of miR-218 and immunocytochemical stain of CDK6 and Ki-67, respectively. Single cell gel electrophoresis was used to detect the presence of apoptotic cell.

RESULTSThe miR-218 labeling indexes (LI) were statistically different (P<0.05) among all groups including control (22.45 +/- 0.59) and various glioma groups (grades I - II 4.00 +/- 1.07, grade III 1.87 +/- 1.06 and grade IV 0.94 +/- 0.78, respectively). The CDK6 LI of the four groups was 7.25 +/- 1.20, 16.71 +/- 0.80, 24.43 +/- 0.62 and 32.05 +/- 0.43, respectively. Significant differences existed between the control group and the glioma groups, and between grade IV and grades I - II glioma groups (P<0.01). Ki-67 positive cell densities of the above four groups (0.00 +/- 0.00, 9.30 +/- 3.48, 31.15 +/- 9.44 and 60.15 +/- 13.60) were significantly different from one and another (P<0.01). The expression of miR-218 negatively correlated with CDK-6 LI (r = -0.480, P<0. 01) and Ki-67 positive cell density (r = - 0.534, P<0.01), while the latter two positively correlated with each other (r = 0.530, P<0.01). U87MG transfection experiment showed that the miR-218 level of the mimics group was significantly higher than that of the control group (P<0.01). CDK6 and Ki-67 LI of the mimics group (14.74 +/- 1.19 and 30.88 +/- 3.31) were significantly lower than those of the control group (79.06 +/- 2.07 and 64.94 +/- 3.96, P<0.01), whilst its apoptotic index (AI) (68.44 +/- 7.05) was significantly higher than that of the control group (13.04 +/- 0.97, P<0.01).

CONCLUSIONSThe expression level of miR-218 is an important reference indicator for the assessment of the grade of gliomas. An aberrant decrease of its expression may lead to an increase of the CDK6 expression and proliferative activity of giloma cells. Introducing exogenous miR-218 may effectively down-regulate the CDK6 expression, inhibit cell proliferation and induce apoptosis of malignant giloma cells. These findings imply that miR-218 may serve as a therapeutic agent against malignant glioma.

Adolescent ; Adult ; Apoptosis ; Astrocytoma ; metabolism ; pathology ; Brain Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Child ; Cyclin-Dependent Kinase 6 ; metabolism ; Ependymoma ; metabolism ; pathology ; Female ; Glioblastoma ; metabolism ; pathology ; Glioma ; metabolism ; pathology ; Humans ; Ki-67 Antigen ; metabolism ; Male ; MicroRNAs ; metabolism ; Middle Aged ; Neoplasm Grading ; Oligodendroglioma ; metabolism ; pathology ; Transfection ; Young Adult

OBJECTIVETo study the incidence of 53BP1 gene mutations in prostatic adenocarcinoma and benign prostatic hypertrophy, and to analyze the relationship between 53BP1 mutations and prostatic adenocarcinoma.

METHODSGenomic DNA extraction, PCR amplification and gene sequencing were used to detect the occurrence of 53BP1 gene mutations in 50 cases of prostatic adenocarcinoma. Ten cases of benign prostatic hypertrophy were included as controls.

RESULTSAmongst the 50 cases of prostatic adenocarcinoma studied, 15 showed genetic alterations of 53BP1, including 4 cases with single nucleotide polymorphism. The mutation rate was 24.0% (12/50). Seven of the 53BP1 mutations detected represented missense mutations and none of them were situated in functionally important domains. The other 4 were synonymous mutations, in which c. 4760G > T was situated in Tudor domain. There was no obvious correlation between 53BP1 gene mutations and the various clinicopathologic parameters of prostate adenocarcinoma (P>0.05).

CONCLUSIONCertain percentage of prostatic adenocarcinoma harbors 53BP1 mutations which may be involved in the carcinogenesis.

Adenocarcinoma ; genetics ; pathology ; Aged ; Exons ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Middle Aged ; Mutation ; Mutation Rate ; Mutation, Missense ; Polymorphism, Single Nucleotide ; Prostatic Hyperplasia ; genetics ; Prostatic Neoplasms ; genetics ; pathology ; Tumor Suppressor p53-Binding Protein 1

OBJECTIVETo investigate the clinicopathological features, histogenesis and prognosis of mucinous tubular and spindle cell carcinoma (MTSCC).

METHODSFive MTSCCs were studied with histochemical, immunohistochemical staining, electron microscopy, and review of the related literatures.

RESULTSFour cases of MTSCC were females and one was male. Three patients presented with flank discomfort and two were incidentally found with health examination. In gross examination, the tumors were circumscribed. The cut surface was solid, gray-white, yellow or red. Necrosis was present in one case of high-grade MTSCC. Microscopically, low-grade MTSCC was mainly consisted of tubular, spindle cell and mucinous stroma with relatively bland morphology, and mitoses were rare. While in the high-grade area of one case, the cells were spindle or polymorphic with severe atypia and high mitotic activity, without mucinous stroma and tubular structure. Mucin was positive for Alcian blue. The neoplastic cells were positive for vimentin (5/5), CKpan (5/5), CK7 (5/5), CK19 (5/5), 34betaE12 (1/5), EMA (5/5), E-cadherin (3/5), CD10 (1/5), P504S (5/5), and CAM5.2 (5/5). The Ki-67 index was low (< or = 5%) in the low-grade component, while it was high (15%) in the high-grade component. Ultrastructural study showed short microvilli along glandular lumens. The nuclear membrane was focally invaginated. Four cases were followed up for 3 to 52 months, and recurrence and metastasis were not found.

CONCLUSIONSMTSCC occurs predominantly in females and it is a rare kidney neoplasm. Most of MTSCCs are low-grade and the prognosis is relatively good. However, the patients of high-grade MTSCC should be closely followed up.

Adenocarcinoma ; metabolism ; pathology ; surgery ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; surgery ; Adult ; Carcinoma ; metabolism ; pathology ; surgery ; Carcinoma, Medullary ; pathology ; Carcinoma, Renal Cell ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Humans ; Keratins ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Leiomyosarcoma ; metabolism ; pathology ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Nephrectomy ; Racemases and Epimerases ; metabolism ; Vimentin ; metabolism

OBJECTIVETo investigate the clinical and pathological features of the mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney.

METHODSSeven cases of MTSCC were analyzed by gross examination and light microscopy. Immunostaining was performed to detect the expression of CD10, CK7, CK18, CK19, Villin, EMA, P504S and vimentin. The literature on this tumor was reviewed to discuss the histological features of MTSCC and its clinical behavior.

RESULTSThree of 7 cases were male and the other 4 were female. The mean age of the patients was 48.2 years old, with a range from 39 to 61 years. All the patients presented no symptom and their tumors were found by health examination. Tumors averaged 5.5 cm in greatest dimension (range from 4.0 cm to 9.0 cm). The tumors were well-circumscribed without capsules, and the cut surfaces were solid and soft with white-tan color. By light microscopy, tumors were composed of tightly packed, small, elongated tubules with transitions to spindle cell components. Five cases had mucinous stroma. Clear cell clusters, focal sarcomatoid differentiation, papillations and foamy macrophages were seen in several cases. Immunohistochemically, all 7 cases showed positive for CK7, five of 5 cases positive for EMA, CK18 and P504S, four of 5 cases positive for CK19, but heterogeneous for CD10, villin and vimentin expression. No evidence of local recurrence or distant metastases was identified in the 5 patients with follow-up information.

CONCLUSIONSThe mucinous tubular and spindle cell carcinoma is a low-grade and polymorphic neoplasm. The morphology of these tumors may not be uniform with a wide histological spectrum. The tumors can be tubular predominant or spindle cells predominant with scant to abundant mucinous stroma, which coupled with the presence of other unusual features such as clear cells, papillations, foamy macrophages, necrosis and sarcomatoid differentiation. Immunohistochemically, MTSCC can express the markers from the proximal convoluted tubules to collecting tubules.

Adenocarcinoma ; metabolism ; pathology ; surgery ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; surgery ; Adenoma ; pathology ; Adult ; Carcinoma ; metabolism ; pathology ; surgery ; Carcinoma, Renal Cell ; pathology ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Keratin-18 ; metabolism ; Keratin-7 ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Nephrectomy ; Prognosis ; Racemases and Epimerases ; metabolism

Aneuploidy ; Gene Rearrangement ; Glutathione S-Transferase pi ; metabolism ; Humans ; Male ; Methylation ; Neoplasm Grading ; Neoplasm Staging ; Neoplasms, Multiple Primary ; genetics ; metabolism ; pathology ; surgery ; Oncogene Proteins, Fusion ; genetics ; Prostate-Specific Antigen ; metabolism ; Prostatic Intraepithelial Neoplasia ; genetics ; pathology ; Prostatic Neoplasms ; genetics ; metabolism ; pathology ; surgery