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Role of matrix metalloproteinase (MMP)-2 and -9 and vascular endothelial growth factor C in lymph node metastasis of breast cancer.

Shao-qiu ZHENG ; Rong-quan HUANG ; Ya-jie ZHANG

Chinese Journal of Pathology.2010;39(4):240-244.

OBJECTIVETo study the expression of matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF)-C in breast cancer and their role in lymph node metastasis.

METHODSImmunohistochemical staining was used to detect the expression of VEGF-C, MMP-2, MMP-9 and LYVE-1 in 84 cases of breast cancer, including 52 cases with and 32 cases without lymph node metastases. The recombinant vector (pSIREN-VEGF-C) was transfected into human breast cancer cell MCF-7 by liposome, and the RNA expression of MMP-2, MMP-9 and VEGF-C in MCF-7 cells after transfection was detected by PCR.

RESULTSThe expressions of MMP-2, MMP-9 and VEGF-C were 98.1% (51/52), 88.5% (46/52), and 94.2% (49/52) respectively for the metastatic group, and 75.0% (24/32), 53.1% (17/32), and 65.6% (21/32) respectively for the non metastatic group, and there was significant difference between these groups (P < 0.05). The lymphatic vessel density between these two groups was also significantly different (P < 0.05). Increased expression of MMP-2, MMP-9 and VEGF-C was also associated with increased number of lymphatic vessels had also increased (P < 0.05). The expression of MMP-2, MMP-9 and VEGF-C in MCF-7 cells after gene transfection decreased significantly (P < 0.05).

CONCLUSIONMMP-2 and MMP-9 in conjunction with VEGF-C, promote lymphangiogenesis and lymph node metastasis of breast cancer.

Adult ; Aged ; Breast Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; surgery ; Carcinoma, Medullary ; genetics ; metabolism ; pathology ; surgery ; Cell Line, Tumor ; Female ; Humans ; Lymph Nodes ; metabolism ; pathology ; Lymphangiogenesis ; Lymphatic Metastasis ; Lymphatic Vessels ; metabolism ; pathology ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Middle Aged ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Recombinant Proteins ; genetics ; metabolism ; Transfection ; Vascular Endothelial Growth Factor C ; genetics ; metabolism ; Vesicular Transport Proteins ; metabolism

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Clinicopathologic features of 66 cases of anaplastic lymphoma kinase positive and negative systemic anaplastic large cell lymphoma: a comparative study.

Yan SHI ; Gang CHEN ; Xiao-ge ZHOU ; Li-ping GONG ; Ran YU ; Yuan-yuan ZHENG ; Jian-lan XIE ; Yan JIN

Chinese Journal of Pathology.2010;39(4):235-239.

OBJECTIVETo study the clinicopathologic features of 66 cases of primary systemic anaplastic large cell lymphoma (ALCL), with emphasis on the differences between ALK-positive and ALK-negative cases.

METHODSThe clinical data of 66 cases of ALCL was analyzed. The histologic features were reviewed. Immunohistochemical study for CD30, ALK protein, epithelial membrane antigen, CD2, CD3, granzyme B and TIA-1 was carried out. In-situ hybridization for small mRNA of Epstein-Barr virus (EBER) was also performed. The chromosomal abnormalities were studied by fluorescence in-situ hybridization (FISH). The differences between ALK-positive and ALK-negative cases were statistically analyzed.

RESULTSThere were 48 cases of ALK-positive ALCL and 18 cases of ALK-negative ALCL. The patients with ALK-positive ALCL were younger than those with ALK-negative ALCL (P < 0.05), with the median age being 18 years and 36 years, respectively. Fever, especially hyperpyrexia, was more commonly observed in ALK-positive ALCL patients than in ALK-negative ALCL patients (33 cases versus 4 cases, P < 0.05). The overall survival rate and median duration of survival in patients with ALK-positive ALCL were higher and longer than those in patients with ALK-negative ALCL (80% versus 71%; 21 months versus 12.5 months, P > 0.05). There were however no significant differences in histology between ALK-positive ALCL and ALK-negative ALCL. Histologically, most cases showed diffuse growth pattern. Nodular pattern was demonstrated in a minority of cases. "Hallmark" cells were seen in most of the ALCL cases. Focal necrosis and myxomatous stroma were identified in a few cases. Most ALK-positive cases belonged to the common variant (35 cases). A small number represented lymphohistiocytic variant (8 cases). Small cell variant and sarcomatoid subtype were found only in few cases (3 cases and 2 cases, respectively).On the other hand, common variant (17 cases) constituted the majority of ALK-negative ALCL. Lymphohistiocytic variant was seen in only 1 case. Immunohistochemical study showed that ALK-positive ALCL always expressed CD30 and epithelial membrane antigen. ALK-positive ALCL more often expressed epithelial membrane antigen (100% versus 72%; P < 0.05) but less so for T-cell markers (including CD2, CD3, CD43 and CD45RO). Cytotoxic molecules were more commonly expressed in ALK-positive ALCL (P > 0.05). EBER was negative in all cases studied. FISH showed that in ALK-positive ALCL, 1 case had normal ALK gene, 1 had deletion and multicopy and 2 had deletion. On the other hand, 1 case of ALK-negative ALCL had normal ALK gene.

CONCLUSIONSWhile there are no significant morphologic differences between ALK-positive ALCL and ALK-negative ALCL, the clinical features, immunophenotypes and genetic features of both groups vary. These differences are helpful in guiding the differential diagnosis.

Adolescent ; Adult ; Age Factors ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Gene Deletion ; Humans ; Ki-1 Antigen ; metabolism ; Lymphoma, Large-Cell, Anaplastic ; complications ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Malignant Hyperthermia ; etiology ; Middle Aged ; Mucin-1 ; metabolism ; Neoplasm Recurrence, Local ; Protein-Tyrosine Kinases ; genetics ; metabolism ; Receptor Protein-Tyrosine Kinases ; Survival Rate ; Young Adult

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Cutaneous anaplastic large cell lymphoma: clinicopathologic, immunohistochemical and prognostic study of 44 cases.

Yun-yi KONG ; Bo DAI ; Jin-cheng KONG ; Hong-fen LU ; Da-ren SHI

Chinese Journal of Pathology.2010;39(4):230-234.

OBJECTIVETo study the clinicopathologic features, immunophenotype and prognosis of primary cutaneous anaplastic large cell lymphoma (CALCL).

METHODSHistopathologic evaluation and immunohistochemical study by Envision method were carried out in 44 archival cases of CALCL. The clinical information and follow-up data were analyzed.

RESULTSThe patients presented with skin nodules, masses or plaques, sometimes associated with ulceration. The commonest sites of involvement were the extremities. Follow-up data were available in 39 patients. The overall survival rate was 87.2% (34/39). Disease relapses were detected in 46.2% (18/39) of the patients. Statistical analysis indicated that patients older than 50 years of age or with no less than two involved anatomic sites were more likely to have disease relapses (P < 0.05). Histologically, 31 cases were classified as common variant, 6 cases as small cell variant and 7 cases as neutrophil/eosinophil-rich variant. Immunohistochemical study showed that the rates of expression of CD30, CD45, CD45RO, CD43, CD3, cytotoxic protein and epithelial membrane antigen were 100% (44/44), 91.2% (31/34), 82.6% (19/23), 94.7% (18/19), 70.0% (28/40), 73.3% (22/30) and 31.8% (7/22), respectively. The CD4(+)/CD8(-), CD4(-)/CD8(+) and CD4(-)/CD8(-) immunophenotypes were found in 58.3% (21/36), 22.2% (8/36) and 19.4% (7/36) of the CALCL cases, respectively. Only one case (3.7%) expressed CD56.

CONCLUSIONSCALCL is a form of low-grade primary cutaneous T-cell lymphoma with a wide spectrum of clinicopathologic pattern. Special variants of CALCL should not be confused with other types of cutaneous lymphomas and inflammatory lesions. CALCL patients older than 50 years of age or with no less than two involved anatomic sites are more likely to have disease relapses.

Adult ; Age Factors ; Aged ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Immunophenotyping ; Ki-1 Antigen ; metabolism ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Lymphoma, Primary Cutaneous Anaplastic Large Cell ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Proportional Hazards Models ; Skin Neoplasms ; drug therapy ; metabolism ; pathology ; Survival Rate ; Young Adult

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Application of Warthin-Starry stain, immunohistochemistry and transmission electron microscopy in diagnosis of cat scratch disease.

Juan HUANG ; Lin DAI ; Song LEI ; Dian-ying LIAO ; Xiao-qing WANG ; Tian-you LUO ; Yu CHEN ; Zhen-biao HANG ; Gan-di LI ; Dan-dan DONG ; Gang XU ; Zheng-ce GU ; Ji-ling HAO ; Ping HUA ; Lei HE ; Fang-lei DUAN

Chinese Journal of Pathology.2010;39(4):225-229.

OBJECTIVETo evaluate the diagnostic utility of Warthin-Starry silver stain, immunohistochemistry and transmission electron microscopy in the detection of human Bartonella henselae infection and pathologic diagnosis of cat scratch disease (CSD).

METHODSThe paraffin-embedded lymph node tissues of 77 histologically-defined cases of cat scratch disease collected during the period from January, 1998 to December, 2008 were retrieved and studied using Warthin-Starry silver stain (WS stain) and mouse monoclonal antibody against Bartonella henselae (BhmAB stain). Five cases rich in bacteria were selected for transmission electron microscopy.

RESULTSUnder electron microscope, the organisms Bartonella henselae appeared polymorphic, round, elliptical, short rod or bacilliform shapes, ranged from 0.489 to 1.110 microm by 0.333 to 0.534 microm and often clustered together. Black short rod-shaped bacilli arranged in chains or clumps were demonstrated in 61.0% (47/77) of CSD by WS stain. The organisms were located outside the cells and lie mainly in the necrotic debris, especially near the nodal capsule. In 72.7% (56/77) of the cases, dot-like, granular as well as few linear positive signals were observed using BhmAB immunostain and showed similar localization. Positive results for both stains were identified in 59.7% (46/77) of the cases. When applying both stains together, Bartonella henselae was observed in 74.0% (57/77) of the case. The difference between the results obtained by WS stain and BhmAB immunostain was of statistical significance (P < 0.05).

CONCLUSIONSBartonella henselae is the causative pathogen of cat scratch disease. WS stain, BhmAB immunostain and transmission electron microscopy are helpful in confirming the histologic diagnosis. Immunostaining using BhmAB can be a better alternative than WS stain in demonstrating the organisms.

Adolescent ; Adult ; Aged ; Antibodies, Bacterial ; blood ; Bartonella henselae ; immunology ; isolation & purification ; ultrastructure ; Cat-Scratch Disease ; diagnosis ; microbiology ; pathology ; Child ; Child, Preschool ; Humans ; Immunohistochemistry ; methods ; Infant ; Lymph Nodes ; pathology ; ultrastructure ; Microscopy, Electron, Transmission ; Middle Aged ; Paraffin Embedding ; Staining and Labeling ; methods ; Young Adult

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Clinical significance and pathological evaluation of neoadjuvant chemotherapy in breast cancer.

Li-rong CHEN

Chinese Journal of Pathology.2010;39(4):218-221.

Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Agents, Hormonal ; therapeutic use ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; ultrastructure ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; ultrastructure ; Chemotherapy, Adjuvant ; Female ; Humans ; Neoadjuvant Therapy ; Nitriles ; therapeutic use ; Taxoids ; therapeutic use ; Trastuzumab ; Treatment Outcome ; Triazoles ; therapeutic use

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Tasks and challenges.

Jie CHEN

Chinese Journal of Pathology.2010;39(4):217-217.

Animals ; Biological Specimen Banks ; China ; Humans ; Immunohistochemistry ; standards ; Pathology ; standards ; trends ; Pathology, Clinical ; standards ; trends ; Quality Control ; Translational Medical Research

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Recent advance in von Hippel-Lindau syndrome-related and sporadic hemangioblastomas of central nervous system.

Jing ZHOU ; Nan-yun LI ; Xiao-jun ZHOU

Chinese Journal of Pathology.2010;39(3):212-215.

Antigens, CD34 ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; Central Nervous System Neoplasms ; metabolism ; pathology ; surgery ; ultrastructure ; Diagnosis, Differential ; Ependymoma ; metabolism ; pathology ; Hemangioblastoma ; metabolism ; pathology ; surgery ; ultrastructure ; Humans ; Meningeal Neoplasms ; metabolism ; pathology ; Meningioma ; metabolism ; pathology ; Mutation ; Neoplasm Recurrence, Local ; Prognosis ; Receptor, Epidermal Growth Factor ; metabolism ; Vimentin ; metabolism ; von Hippel-Lindau Disease ; genetics ; metabolism ; pathology ; surgery

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Recent advance in tuberous sclerosis-related genes and their expression.

Jing LIU ; Yue-shan PIAO ; De-hong LU

Chinese Journal of Pathology.2010;39(3):210-212.

Adenocarcinoma ; genetics ; metabolism ; Angiomyolipoma ; etiology ; Antibiotics, Antineoplastic ; therapeutic use ; Astrocytoma ; etiology ; Brain Neoplasms ; etiology ; Breast Neoplasms ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Kidney Neoplasms ; etiology ; Lung Neoplasms ; genetics ; metabolism ; Mutation ; Sirolimus ; therapeutic use ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; metabolism ; Tuberous Sclerosis ; complications ; drug therapy ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

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Neoplasms with perivascular epithelioid differentiation.

Qi-xing GONG ; Qin-he FAN

Chinese Journal of Pathology.2010;39(3):205-209.

Carcinoma, Renal Cell ; pathology ; Diagnosis, Differential ; Digestive System Neoplasms ; pathology ; Female ; Gastrointestinal Stromal Tumors ; pathology ; Humans ; Kidney Neoplasms ; pathology ; Leiomyoma ; pathology ; Male ; Melanoma ; pathology ; Perivascular Epithelioid Cell Neoplasms ; pathology ; Sarcoma, Clear Cell ; pathology ; Sarcoma, Endometrial Stromal ; pathology ; Skin Neoplasms ; pathology ; Soft Tissue Neoplasms ; pathology ; Uterine Neoplasms ; pathology

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Spindle cell tumors of central nervous system.

Qing LI

Chinese Journal of Pathology.2010;39(3):202-204.

Antigens, CD34 ; metabolism ; Astrocytoma ; metabolism ; pathology ; Carcinoma ; metabolism ; pathology ; Central Nervous System Neoplasms ; metabolism ; pathology ; Ependymoma ; metabolism ; pathology ; Fibroma ; metabolism ; pathology ; Ganglioglioma ; metabolism ; pathology ; Glial Fibrillary Acidic Protein ; metabolism ; Glioma ; metabolism ; pathology ; Gliosarcoma ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Neoplasms, Neuroepithelial ; metabolism ; pathology ; Solitary Fibrous Tumors ; metabolism ; pathology

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