BACKGROUND: In multiple lung cancers (MLCs), distinction between intrapulmonary metastases and multiple primary tumors is important for staging and prognosis. In this study, we have investigated histopathologic prognostic factors of patients with MLCs. METHODS: Histologic subtype, size differences, lobar location, lymphovascular invasion (LVI), size of the largest tumor, nodal status, number of tumors, morphology of tumor periphery, and immunohistochemical profiles using eight antibodies, were analyzed in 65 patients with MLCs. RESULTS: There was no significant difference in the survivals of patients with multiple primary tumors and intrapulmonary metastases, as determined by the Martini-Melamed criteria (p=0.654). Risk grouping by four histologic parameters, LVI, margin morphology, size differences, and lobar locations of paired tumors were prognostic. The patients with one or two of aforementioned parameters had significantly longer survival than those with three or four parameters (p=0.017). In patients with largest mass (< or =5 cm), the risk grouping was found to be an independent prognostic factor (p=0.022). However, differences in immunohistochemical staining were not related to patients' survival. CONCLUSIONS: A risk grouping of MLC patients by using combinations of histologic parameters can be a useful tool in evaluating the survival of patients with MLCs, and may indicate clonal relationship between multiple tumors.
Antibodies ; Humans ; Lung ; Lung Neoplasms ; Neoplasm Metastasis ; Prognosis

Vitiligo is a disease in which melanocytes are selectively destroyed. The disease is thought to be an autoimmune process being there are antibodies to pigment cells in the sera of patients and animals with vitiligo. In the present study, sera from vitiligo patients were examined for reactivity with the human melanoma cell line, SK-Mel-28, by Western blot analysis of solubilized membrane antigens of these cells to identify the pigment cell antigens defined by antibodies in the patients with vitiligo. Antibody reactivity to human melanoma cells (SK-Mel-28) was investigated in 14 patients with vitiligo, and 16 with normal control individuals. Antibodies to the 116-113, 60, 40 KD antigens were associated with vitiligo being present in 79%, 86%, and 43% respectively of the patients with vitiligo, but in only 6%, 38% and 6% of the normal controls. In contrast, antibodies to the 160-155, 78 and 64 KD antigens were equally common in vitiligo and in normal individuals. The results suggest that autoreactivity to pigment cells occurs more commonly in patients with vitiligo than in the normal control and high autoreactivity to pigment cells in the vitiligo sera might be an impertinent epiphemenon to destroyed pigment cell.
Antibodies, Neoplasm/*blood ; Antigens, Neoplasm/immunology ; Autoantibodies/blood ; Blotting, Western ; Human ; Melanoma/*immunology ; Vitiligo/*immunology

Angiopoietin2( ANGPT2 ) plays an important role in tumor angiopoiesis. ANGPT2 antagonises ANGPT1 resulting in an effect on the stability of blood vessels, which promotes tumor growth, invasion, proliferation as well as relating to tumor vascular density. A lot of researches published papers about anti-ANGPT2 for the treatment of tumor, and have made some progresses. In this review, the role of ANGPT2 in the pathogenesis of acute myelogenous leukemia (AML), including its effects on proliferation of leukemia cells, bone marrow angiopoiesis, tumor invasion and metastasis are briefly summarised in order to provide the basis for targeted ANGPT2 in treatment of AML.
Angiopoietin-1 ; immunology ; Antibodies ; immunology ; Bone Marrow ; Humans ; Leukemia, Myeloid, Acute ; immunology ; Neoplasm Invasiveness ; Neoplasm Metastasis

Monoclonal antibodies (MoAbs) have different mechanism and adverse effects compared with cytotoxic agents. The introduction of MoAbs has improved the treatment potency to malignant lymphoma without decreasing the quality of life. However, there are many questions to be answered: What is the profound mechanism of MoAbs? How about their long-term adverse effects? What is the best medication pattern in different disease types?
Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Murine-Derived ; Antibodies, Neoplasm ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Drug Delivery Systems ; methods ; Drug Design ; Humans ; Lymphoma ; therapy ; Radioimmunotherapy ; Rituximab

BACKGROUND: One of the most important prognostic factors in colorectal cancer is lymph node metastasis, which predicts a reduced survival time. Although lymph node metastases were not detected by a conventional hematoxylin-eosin stain technique, 20 to 30 percent of patients fail long-term survival on account of a local or systemic recurrence. Recurrent disease in these patients is believed to develop from occult tumor in lymph nodes. PURPOSE: The authors have conducted an immunohistochemical study with two different antibodies against cytokeratin to identify occult micrometastases in lymph nodes which were diagnosed as tumor negative by conventional histopathology. METHODS: Paraffin blocks of sixty-five patients with colorectal cancer (T2/3, N0, M0) after a curative resection between January 1991 and December 1993 at Kyung-Hee University Hospital were stained with avidin-biotin-peroxidase complex technique using two monoclonal antibodies (anti-cytokeratin AE1/AE3 and anti-cytokeratin No. 20, DAKO, Hamburg, Germany). To assess the clinical correlation between micrometastasis in lymph node and patients survial, 5-year disease-free survival rates were calculated by Kaplan-Meier method and the significance of the differences was estimated by the log-rank test. P values <0.05 were taken to be significant. RESULTS: Of the sixty-five patients with 1133 lymph nodes, tumor cells detected by anti-cytokeratin AE1/AE3 and anti-cytokeratin No. 20, were 2.4 percent (27/1133) and 3.4 percent (38/1133), respectively. Micrometastases were detected in twenty-six patients (40.0 percent). The histologic stage of four cytokeratin positive cases was upstaged from T2, N0, M0 to T2, N1/2, M0, and twenty-two of T3, N0, M0 to T3, N1/2, M0. Cytokeratin-positive cases showed statistically significant recurrence rate (42.3 percent) compared to that of cytokeratin -negative cases (17.9 percent)(x2 test, p=0.032). With the median follow-up of 62 months, 5-year disease-free survival rates of the micrometastses negative and positive cases were 81.7 percent and 61.3 percent, respectively (p=0.0438). CONCLUSIONS: In conclusion, immunohistochemical technique to identify the occult micrometastases in lymph nodes overlooked in conventional histopathology is a useful staging method to anticipate a recurrence and a prognosis more precisely.
Antibodies ; Antibodies, Monoclonal ; Colorectal Neoplasms* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Keratins ; Lymph Nodes ; Neoplasm Metastasis ; Neoplasm Micrometastasis* ; Paraffin ; Prognosis ; Recurrence

Matrix metalloproteinase(MMP) is the proteolytic enzyme of the extracellular matrix. MMPs play a role in the invasion and metastasis of malignant tumor, but it is not known whether the expression of MMPs in squamous cell carcinoma of the tongue is related to the prognostic factors of this tumor. In this study, 32 paraffin-embedded tumor specimens were examined immunohistochemically using monoclonal antibodies of MMP-2, MMP-3, MMP-10 and MMP-13. The possible relationships between the expressions of the MMPs and TNM staging, the differentiation of tumor cells, size of tumor mass and lymph node metastasis were anlaysed statistically. The results were as follows. 1. The expression of MMP-2 increased according to TNM staging (P < 0.05) and lymph node metastasis (P < 0.05) and the expression of MMP-2 was not affected by the differentiation of tumor cells or tumor size. 2. The expression of MMP-3 increased with increasing tumor size (P < 0.05). However it was not related to TNM staging, the differentiation of tumor cells or lymph node metastasis. 3. The expression of MMP-10 was unrelated to TNM staging, differentiation of tumor cells, lymph node metastasis or tumor size. 4. The expression of MMP-13 increased as tumor size increased (P < 0.05). However it was not related to TNM staging, the differentiation of tumor cells or lymph node metastasis. We concluded that the expression patterns of MMP-2, MMP-3, and MMP-13 may play a role in the diagnosis, treatment plan and prognostic evaluation of malignant tumors of the tongue.
Antibodies, Monoclonal ; Carcinoma, Squamous Cell* ; Diagnosis ; Extracellular Matrix ; Lymph Nodes ; Matrix Metalloproteinases ; Neoplasm Metastasis ; Neoplasm Staging ; Tongue*

Mortality associated with human breast carcinoma is almost entirely due to subsequent cancer metastasis, but the molecular basis of this metastasis is not well established. The nm23 gene was originally identified by differential hybridization between two murine melanoma cell sublines which have low and high metastatic potential, and located in chromosome 17q22. This gene has been known to be involved in the metastasis of several cancers and its down-regulation usually associated with metastasis or disease progression in breast cancer. Tumor angiogenesis, the process leading to the formation of new vessels, plays a central role in tumor progression and distant metastasis. It is implicated in the phenomenon of dormant micrometastasis. This study was designed to determine the prognostic value of expression of the nm23 protein and tumor angiogenesis in breast cancer. Also, these two factors were compared with established clinicopathological prognostic factors and hormone receptors. 118 paraffin embedded surgical specimens of breast cancer were obtained from March, 1988 to February, 1994 and were selected for study. The expression of nm23 protein was studied by using immunohistochemical staining with anti-nm23/nuclear diphosphate kinase A. Tumor angiogenesis was quantified under light microscope by counting of the tumor microvessels(MVC) which were highlighted with anti-CD31 antibodies. The patient were allocated into two groups by mean number of MVC, one group was less 42 and the other was over 42. All the patients were female. The nm23 protein expression was positive in 74(63%) cases and was negative in 44(37%) cases. There was a significant correlation between nm23 protein expression and histologic grade(p=0.023). Positive expression of nm23 protein was correlated with positive estrogen(p=0.031) and progesterone receptors(p=0.001). Also Positive expression of nm23 protein was correlated with longer disease free survival(p=0.0026) and overall survival(p=0.0048). The group of MVC<42 showed better survival in overall(p=0.0195) and disease free survival(p=0.0014) than the other group of MVC>42. But the MVC and established clinicopathological prognostic factors did not show any correlation, neither with hormone status. When the nm23 protein and angiogenesis were considered together, 50 cases of negative nm23 protein and MVC<42 showed the best survival in overall(p=0.0111) and disease free survival(p=0.0114) among the four groups of each combination. In conclusion, the expression of nm23 protein and tumor angiogenesis can be used as new prognostic factors in conjunction with established other prognostic factors.
Antibodies ; Breast Neoplasms* ; Breast* ; Disease Progression ; Down-Regulation ; Female ; Humans ; Melanoma ; Mortality ; Neoplasm Metastasis ; Neoplasm Micrometastasis ; Paraffin ; Phosphotransferases ; Progesterone

Although causative factors are not completely defined, carcinogenesis of colorectal cancer is attributed to multiple genetic alterations. The abnormal expressions of oncogenes are regarded to be responsible for the production of malignant phenotype, subsequent invasion and metastasis. From 63 surgically resectable colorectal adenocarcinoma patients, expression of oncogenes in colorectal cancer tissue was evaluated with immunohistochemical staining methods using monoclonal antibodies to products of the oncogenes. To evaluate the possibility of oncogenes as a prognostic factor, we studied the relationship between the expression of oncogenes and the clinicopathologic findings which are well known prognostic factors. Rates of expression in colorectal cancer tissue were 27% for c-myc, 74.6% for c-Ha-ras and 77.8% for c-erbB-2 oncogenes. The positive rate of c-erbB-2 oncogene was higher in the well differentiated group than in the poorly differentiated group. The rates of expression of c-myc and c-Ha-ras oncogenes were significantly correlated each other. Expression of these oncogenes in colorectal cancer were not correlated with the pathologic stage, location of cancer, DNA ploidy pattern and histologic differentiation except between c-erbB-2 and histologic differentiation. In conclusion, there seems to be a possibility that c-erbB-2 could be used as a prognostic factor of colorectal cancer. However, further and more intensive study seems to be required.
Adenocarcinoma ; Antibodies, Monoclonal ; Carcinogenesis ; Colorectal Neoplasms* ; DNA ; Humans ; Neoplasm Metastasis ; Oncogenes* ; Phenotype ; Ploidies

Dysregulated receptor tyrosine kinase signaling in human cancer cells leads to tumor progression, invasion and metastasis. The receptor tyrosine kinase cMET is frequently overexpressed in cancer tissue, and activation of cMET signaling is related to drug resistance and the processes of carcinogenesis, invasion and metastasis. For that reason, cMET and its ligand, hepatocyte growth factor (HGF), are considered prime targets for the development of anticancer drugs. At least eight anti-cMET and four anti-HGF antibodies have been tested or are being tested in clinical trials. However, to date none of these HGF/cMET inhibitors have shown significant efficacy in clinical trials. Furthermore, no receptor tyrosine kinase inhibitors primarily targeting cMET have been approved. Given that neutralization of HGF or cMET does not cause significant adverse effects, inhibition of the HGF/cMET signaling pathway appears to be safe. In this review, we summarized the completed and ongoing clinical trials testing antibody- or protein-based anticancer drugs targeting cMET and HGF.
Antibodies ; Carcinogenesis ; Drug Resistance ; Hepatocyte Growth Factor ; Humans ; Neoplasm Metastasis ; Protein-Tyrosine Kinases

BACKGROUND: The epithelial-mesenchymal transition (EMT) in epithelial tumor cells plays a key role in tumor invasion and metastasis. The reduction or loss of E-cadherin and the acquisition of vimentin are two critical steps in the EMT. However, the roles of EMT-related proteins in basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) have not been fully elucidated. OBJECTIVE: The purpose of this study was to investigate the immunohistochemical expressions of E-cadherin and vimentin in BCC and SCC, and to demonstrate the EMT and its role in tumor invasion. METHODS: Paraffin-embedded tissues from 30 BCC and 20 SCC cases were incubated with primary antibodies to E-cadherin and vimentin. The co-expression of the biomarkers and the biomarkers' correlations with the histopathological grades were analyzed. RESULTS: E-cadherin expression reduced by 90.0% and 95.0% in BCC and SCC, respectively, and the expression of vimentin increased by 10.0% and 55.0% in BCC and SCC, respectively. The expression of vimentin was significantly different in BCC and SCC (p<0.05). There were no correlations between the expression of E-cadherin and the expression of vimentin in BCC (p>0.05), or between the expression of E-cadherin and the expression of vimentin in SCC (p>0.05). CONCLUSION: These results suggest that the EMT affects the pathophysiology of both BCC and SCC. The greater aberrance in the expression of vimentin in SCC compared with that in BCC might be one factor that underlies the greater aggression of SCC clinically.
Aggression ; Antibodies ; Biomarkers ; Cadherins* ; Carcinoma, Basal Cell* ; Carcinoma, Squamous Cell* ; Epithelial-Mesenchymal Transition* ; Neoplasm Metastasis ; Vimentin*