The discovery of oncogenes and tumor suppressor genes have made it possible to partly understand the mechanism of cancer development. It is generally accepted that the cancer development is caused by specific gene alterations and now more than 100 oncogenes and suppressor genes are known to be involved in human carcinogenesis. However, there are only a few reports about oncogene expression on bone tumors. The author carried out an immunohistochemical study to reveal the oncogene and suppressor genes on carcinogenesis of bone tumors using antibodies against c-myc, c-H-ras, p53 and EGF. In 32 cases of osteochondrorma, EGF, p53 and c-myc antisera revealed positive reaction in 4 (12.5%), 2 (6.3%) and 7 (21.9%) cases, and, in 4 cases of chondrosarcoma, c-myc antisera revealed positive reaction in 2 (50%) cases. In 21 cases of osteosarcoma, the positive reaction of p53 was noted in 10 (47.6%) cases and that of c-myc in 3 (14.3%) cases. In 14 cases of fibrous bone tumors, there are only 2 (14.3%) cases of positive reaction with p53. These results suggest some roles of the p53 and c-myc genes in osteosarcoma development and c-myc gene in osteochondroma and chondrosarcoma development.
Antibodies ; Carcinogenesis ; Chondrosarcoma ; Epidermal Growth Factor ; Genes, myc ; Genes, Suppressor ; Genes, Tumor Suppressor* ; Humans ; Immune Sera ; Oncogene Proteins ; Oncogenes* ; Osteochondroma ; Osteosarcoma

The most important prognostic factor of breast cancer is the status of lymph node or distant metastasis, which is resisted by basement membrane and stromal matrix. MMP (matrix metalloproteinase)-2 is a 72-kilodalton type IV collagenase/ gelatinase and degrades the type IV collagen which is a main component of the basement membrane. Therefore, MMP-2 is believed to be one of the key molecule for cancer invasion and metastasis. Enzymatic activity of MMP is inhibited by TIMPs (tissue inhibitors of metalloproteinase). TIMP-2 forms a complex with latent pro-MMP-2 and inhibits the active forms of MMP-2. The balance of MMPs and TIMPs is suspected as the important factor of invasion and metastasis of the tumor cells. We studied the association between the expression of MMP-2/TIMP-2 and growth pattern of tumor border, lymph node metastasis, and estrogen receptor expression in the 57 cases of invasive ductal carcinoma of the breast using immunohistochemical staining methods. The results revealed increased expression of MMP-2 in the infiltrating tumor border and tumors with positive lymph node metastasis and negative estrogen receptor with no statistical significance (p>0.05). But the expression of TIMP-2 was increased in expanding tumor border and tumors with positive lymph node metastasis and negative estrogen receptor without statistical significance (p>0.05).
Basement Membrane ; Breast Neoplasms ; Breast* ; Carcinoma, Ductal* ; Collagen Type IV ; Estrogens* ; Gelatinases ; Lymph Nodes* ; Matrix Metalloproteinases ; Neoplasm Metastasis* ; Tissue Inhibitor of Metalloproteinase-2*

Natural Killer (NK) cells are a subpopulation of in vivo activated lymphocytes that display spontaneous cytotoxicity against a variety of targets as virus-infeeted, and transformed neoplastic cells, in major histocompatibility-unrestricted fashion. Depression of the NK aetivity in patients with advanced stages of various types of solid neopls,sms appears to be dependent upon the prcgressive growth and metastatic spread of the tumor. There are many reports that different distribution of subpopulations of lymphocytes in neopiastic tissue may influence the prognosis of the patients, In this study, we have performed immunohistochemieal study with Leu-7, MT1, LN2, and antilysozyrne antiserum on the tissue of uterine cervieal dysplasia and cancer to investigate the distribution of the NK cell, T cell, B cell, and macrophage. The results were as follows ; 1. The major subpopulation of lymphocytes infiltrating the lesion of intraepithelial neoplasia and squamous cell carcinama was T cell. 2. The number of infiltrated. lymphocytes was layer in the lesion of keratinzing type than in that of non keratinizing and small cell earcinorna of the uterine cervix. 3. NK cell was more frequently noted in the malignant lesion than the dysplastic lesion.
Cervix Uteri ; Depression ; Female ; Humans ; Killer Cells, Natural ; Lymphocytes ; Macrophages ; Prognosis ; Uterine Cervical Neoplasms*

We investigated the role of the tumor suppressor genes in the germ cell tumor. Immunohistochemistry (IHC) and polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) for p53 mutation were done in 46 cases of the germ cell tumor with paraffin embedded tissue. The immunohistochemical staining for Rb protein was also performed in the same specimens. The following results were obtained. The overexpression of the p53 protein was detected in 7 of 46 cases (15%). p53 mutation by PCR-SSCP was detected in 1 of 46 cases (2.2%). Expression of Rb protein was negative in 19 cases (41%). These results suggest that p53 mutation does not play an important role in the initiation and progression of germ cell tumors.
Genes, Tumor Suppressor ; Germ Cells* ; Immunohistochemistry ; Neoplasms, Germ Cell and Embryonal* ; Paraffin ; Retinoblastoma Protein*

In the normal disc tissue, the blood vessles have not been observed. It has been suggested that the vascular ingrowth promotes the granulation tissue formation in the herniated disc tissue. The origin of capillaries observed in the herniated disc tissue has remained unclear, but basic fibroblast growth factor(bFGF) may be the important inducer of capillary ingrowth. The purpose of this study is to evaluate the neovascularization in the intervertebral disc without rupture of annulus fibrosus, not being exposed to epidural fat. The disc tissues including nucleus pulposus and annulus fibrosus were obtained at anterior interbody fusion from 30 patients with back pain. All specimens were immediately frozen and stored at -70degrees C. Hematoxylin-eosin stain, polyclonal von Willebrand factor(FVIII) antibody, smooth muscle actin antibody and anti-human endothelial cell antibody(CD31) were used to confirm the blood vessel. Polyclonal bFGF antibody expression was evaluated in the disc tiussues. All of the blood vesseles were observed in the inner portion of annulus fibrosus and the transitional zone. The blood vesseles were observed in 96.7% with hematoxylin-eosin stain, 83.3% with smooth muscle actin antiboy stain, 90% with FVIII, 86.7% with CD31 and the immunopositive blood vesseles were observed in 83.3% with bFGF immunostain. The neovascularization of disc was frequently found in the annulus fibrosus and the transitional zone. The neovasuarlization of intervertebral disc was present in the intervertebral disc without rupture of annulus fibrosus.
Actins ; Back Pain* ; Blood Vessels ; Capillaries ; Endothelial Cells ; Fibroblast Growth Factor 2* ; Fibroblasts ; Granulation Tissue ; Humans ; Intervertebral Disc Displacement ; Intervertebral Disc* ; Muscle, Smooth ; Rupture

Almost all colorectal carcinomas have been thought to develop from pre-existing adenomas. However, some colorectal carcinomas can arise directly from normal flat mucosa, and usually form infiltrative mass at the early stage. The carcinogenesis of this infiltrative carcinoma may be different from the well-known adenoma-carcinoma sequence, which usually forms a polypoid mass. The purpose of this study is to investigate the different expression of various oncogenes in polypoid carcinoma and infiltrative carcinoma. We performed immunohistochemical staining on p53, bcl-2, c-erbB-2 and MIB-1 in 29 polypoid carcinomas arised from adenomas, and 21 infiltrative carcinomas. The average tumor size of infiltrative carcinomas (5.5 cm) was larger than that of polypoid carcinomas (3.1 cm), and the polypoid carcinomas were differentiated more than the infiltrative carcinomas. The results of p53, bcl-2, c-erbB-2, and MIB-1 antisera immunoreactivity in the polypoid carcinoma were 79%, 17%, 21%, and 100%, and those in the infiltrative carcinoma were 71%, 29%, 29%, and 100%, respectively. However the diffuse positivities of p53 and MIB-1 antisera were slightly higher in the infiltraive carcinomas (62%, 76%) than in the polypoid carcinomas (55%, 41%) (p=0.63, 0.01). And the results of p53 and c-erbB-2 immunoreactivity in the adenomas were 52% and 17%, respectively, which is significantly lower than that in the polypoid carcinoma(p=0.03, 0.74). The immunoreactivty of bcl-2 in the adenoma was 72%, which was significantly higher than that in the polypoid carcinoma (17%) (p<0.01). In summary, we did not show the significant difference in expression of p53, bcl-2, c-erbB-2, and MIB-1 proteins between polypoid and infiltrative carcinomas. However, the tendency of infiltrative carcinomas having a more aggressive nature suggests another carcinogenetic mechanism is involved in the colorectal carcinogenesis.
Adenoma ; Carcinogenesis ; Colorectal Neoplasms* ; Immune Sera ; Ki-67 Antigen ; Mucous Membrane ; Oncogenes

No abstract available.
Lung*

Metastasis to the breast from medullary carcinoma of the thyroid is extremely rare. We report a case of metastatic medullary carcinoma of the thyroid which presented as multiple breast masses with ipsilateral axillary lymphadenopathy in a 48-year-old woman. Six years ago, she underwent total thyroidectomy and neck dissection because of palpable neck masses, with a diagnosis of medullary thyroid carcinoma. Histological features of breast masses showed single- file or linear-cord arrangements, with plasmacytoid appearance, and the initial diagnosis was invasive lobular carcinoma. She underwent modified radical mastectomy. The tumor cells were diffusely positive for E-cadherin, calcitonin and thyroid transcription factor-1 (TTF-1) and were metastatic medullary carcinoma of thyroid. In the patients with a history of medullary carcinoma of the thyroid, a careful examination is necessary for a breast mass composed of solid and cord-like clusters of small round to ovoid cells with plasmacytoid appearance. Immunohistochemical staining for E-cadherin, calcitonin and TTF-1 could be helpful for differential diagnosis.
Breast* ; Cadherins ; Calcitonin ; Carcinoma, Lobular* ; Carcinoma, Medullary* ; Diagnosis ; Diagnosis, Differential ; Female ; Humans ; Lymphatic Diseases ; Mastectomy, Modified Radical ; Middle Aged ; Neck ; Neck Dissection ; Neoplasm Metastasis ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroidectomy

BACKGROUND: The colorectal adenoma-carcinoma sequence represents a well-known para-digm for the sequential development of cancer driven by the accumulation of genomic defects. Although the colorectal adenoma-carcinoma sequence has been well investigated, the studies about tumors of different dignity co-existent in the same patient are rare. K-ras mutation is an early genetic change in colon cancer. The genes involved in the cell cycle such as cyclin D1, p16, and p53 are important in the tumorigenesis of the colon. The aims of this study were to determine K-ras gene mutation and expression of K-ras, p16, cyclin D1 and p53 in synchronous lesions of the colon adenoma-carcinoma sequences and their possible relationship with K-ras mutation. METHODS: The materials included 45 colonic adenocarcinomas which were accompanied by adenoma (22 low grade and 26 high grade). By using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP), we detected K-ras mutation of codon 12. An aberrant K-ras, p16, cyclin D1 and p53 expressions were stained using an immunohistochemical method. RESULTS: K-ras mutation was 52.4% (11/21) of high grade adenomas. K-ras expression was 65.4% (17/26) of high grade adenomas. p16 and cyclin D1 expressions were 50% (11/22) and 90.9% (20/22) of low grade adenomas, respectively. p53 expression was 75.6% (34/45) of adenocarcinomas. There were statistical correlations among K-ras, p16 and cyclin D1. CONCLUSIONS: These results indicate that the ras gene mutation is an early event and the overexpressions of p16, cyclin D1 and p53 are associated with K-ras mutation and expression in adenoma-carcinoma sequences.
Adenocarcinoma ; Adenoma ; Carcinogenesis ; Cell Cycle ; Codon ; Colon* ; Colonic Neoplasms ; Colorectal Neoplasms ; Cyclin D1* ; Cyclins* ; Genes, ras* ; Humans

BACKGROUND: Transforming growth factor(TGF-alpha) is a polypeptide which is structurally related to epidermal growth factor(EGF) and binds to the epidermal growth factor receptor(EGFR). TGF-alpha utilizes EGFR to increase the activation of tyrosine kinase to involve in signal transduction of cellular growth. TGF-alpha synthesis occurs in a variety of neoplastic cells. p53 is a tumor-suppressor gene. There is a strong corrleation between immunohistochemical p53 positivity and p53 mutations in lung and laryngeal carcinoma. PCNA is expressed by cycling cells in late G1, S and G2 phase, and may be used to indicate the degree of cellular proliferation. OBJECTIVES: To evaluate whether TGF-alpha, p53 and PCNA can be used as an indicator to malignant transformation of dysplasia in larynx or not. MATERIALS AND METHODS: The authors investigated the TGF-alpha score, p53 immunoreactivity and PCNA proliferating index by immunohistochemical staining in 30 laryngeal dysplasia from 1992 to 1995. RESULTS: Dysplasia with malignant transformation showed values of 5.46 for TGF-alpha, 29.2 for PCNA proliferating index and 37.5 for p53 immunoreactivity. Dysplasia without malignant transformation showed values of 1.88 for TGF-alpha, 8.6 for PCNA proliferating index and 4.5 for p53 immunoreactivity. Conclusions: The results suggest that TGF-alpha, p53 and PCNA could be an useful indicator to predict the progression of laryngeal dysplasia.
Cell Proliferation ; Epidermal Growth Factor ; G2 Phase ; Larynx ; Lung ; Proliferating Cell Nuclear Antigen* ; Protein-Tyrosine Kinases ; Signal Transduction ; Transforming Growth Factor alpha*