There are a lots of evidences that colorectal cancer arise as a result of multiple alterations of genes. Many attempts were made to understand the role of oncogenes and suppressor genes as a prognostic indicator, recently. Although histopathologic staging of tumor is the most important prognostic factor up to now, it is not enough to be used with full confidence. Apoptosis or programmed cell death represents a deletion of damaged or natural cell mechanism. The bel-2 proto-oncogene is known as a inhibitor of apoptosis that may allow accumulation and propagation of cells containing genetic alterations. Overexpression of bcl-2 probably plays a role in colorectal carcinogenesis. The aim of this study was to determine bcl-2 and p53 expression in colorectal carcinoma in correlation with apoptosis, clinical parameters, and histopathology, and to test their prognostic significance in patient with colorectal carcinoma. The bel-2 and p53 protein were identified by immunohistochemical staining using monoclonal and polyclonal antibody. The apoptotic index was detetermined by microscopic examination of hematoxyln and rosin-stained sections at x400. The materials subiected to this study were 54 paraffin-embedded colorectal carcinomas, which were collected randomly from January of 1992 to December of 1994 at Department of Surgery, Chosun University Hospital. Of 54 cases, 21 (38.9%) and 22(40.7%) showed positive expression of bel-2 and p53 protein respectively. Mean apoptotic index(AI) was 2.99% in colorectal carcinoma. Bcl-2 expression did not correlated with p53 expression or apoptotic index. Positive expression of p53 or AI was not correlate with any other clinical and pathologic parameters. An inverse correlation was found between bel-2 expression and increased tumor stage or Iymph node metastasis (P<0.05). In conclusion, these results suggest that bcl-2 expression is significant associated with early stage in colorectal carcinoma. But bcl-2 p53 and AI can`t be a independent prognostic factor in colorectal carcinoma. Further investigations to clarity its possible role in controlling the tumor decelopment and growth of colorectal carcinoma are needed.
Apoptosis ; Carcinogenesis ; Cell Death ; Colorectal Neoplasms* ; Genes, Suppressor ; Humans ; Neoplasm Metastasis ; Oncogenes ; Proto-Oncogenes

PURPOSE: We compared c-erbB-2 oncogene amplification and oncoprotein expression, trying to identify the biologic and prognostic significance of c-erbB-2 in adendegrees Carcinoma of the stomach. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue sections from 43 cases of gastric cancer were analyzed for amplification of c-erbB-2 by differential polymerase chain reaction and for overexpression of gene product by immunohistdegrees Chemistry. RESULTS: The amplification was detected in 13 cases (30%). Enhanced c-erbB-2 immunoreactivity was observed in 30% (13/43) of tumors. Tumors with gene amplification generally stained strongly (p=0.003). Although the frequency of amplification and overexpression of c-erbB-2 was increased with advanced gastric cancer and with lymph node metastasis, this difference was not statistically significant. c-erbB-2 gene amplification or protein overexpression showed a trend toward a better five year survival rate, but this did not reach a statistical significance. CONCLUSION: Amplification and/or overexpression of the c-erbB-2 may be of value in clarifying the biologic characteristics of the human gastric cancer. However, more sensitive and more speci fic methods of identifying gene amplification are needed and the standardization of the staining method as well as guidelines for interpreting the staining result are mandatory for this purpose.
Chemistry ; Gene Amplification ; Genes, erbB-2 ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Oncogenes ; Polymerase Chain Reaction ; Population Characteristics ; Proto-Oncogenes ; Stomach ; Stomach Neoplasms* ; Survival Rate

Although the exact etiology of cutaneous angiosarcoma remains unclear, MYC gene amplification has been recently discovered as a new pathogenesis. MYC is a proto-oncogene, and aberration of MYC signaling in malignancies is associated with tumor metastasis, recurrence, and mortality. Moreover, upregulation of the miRNA polycistron, miR-17-92 cluster, were confirmed in both cutaneous angiosarcoma and multiple myeloma with MYC amplification. The correlation between MYC and miRNA expression is predictable as the coincident aberrant phenotype in two diseases. Moreover, the exploiting MYC dependency may be an attractive disease-specific strategy for the diagnosis and treatment of patients who are unaware of the causes of cutaneous angiosarcoma. Herein, a rare case of cutaneous angiosarcoma of the foot, which is also the first case of cutaneous angiosarcoma accompanied by multiple myeloma, has been described.
Diagnosis ; Foot ; Genes, myc ; Hemangiosarcoma ; Humans ; MicroRNAs ; Mortality ; Multiple Myeloma ; Neoplasm Metastasis ; Phenotype ; Proto-Oncogenes ; Recurrence ; Up-Regulation

The prognosis for gastric adenocarcinoma has been found to be related to several factors such as depth of invasion, inflammatory reaction, lymph node metastasis, pathological stage, DNA ploidy, amplification of proto-oncogene, and tumor suppressor gene. This study was performed to investigate the expression rate of p53 protein and c-erbB-2 oncoproteins in gastric adenocarcinoma, and correlation among clinicopathologic parameters, p53 protein and c-erbB-2. The p53 protein and c-erbB-2 oncoproteins were immunohistochemically stained in the tissue specimens of 36 advanced adenocarcinoma and 15 early adenocarcinoma. The results were summarized as follows; 1) Positive reaction for c-erbB-2 oncoprotein revealed an intense brown granular staining predominantly at the tumor cell membrane, with some cell exhibiting a cytoplasmic staining as well. The surrounding mucosal epithelial cells and protein cells around tumors revealed positive reaction. Positive reaction for p53 protein revealed an intense brown granular staining in tumor nuclei. 2) Twenty four of 51 cases(47%) for p53 protein and 11 of 51 cases(22%) for c-erbB-2 oncoprotein of gastric adenocarcinoma revealed positive reaction. 3) There was no significant difference in the expression of p53 protein and c-erbB-2 according to lymph node metastasis, depth of invasion and Laurens' classification. 4) Five of 51 cases(10%) simultaneously revealed c-erbB-2 oncoprotein overexpression associated with p53 protein expression, and 21 of 51 cases(41%) simultaneously revealed negative reaction for c-erbB-2 oncoprotein and p53 protein. There was no correlation between c-erbB-2 oncoprotein overexpression and p53 protein expression. In summary, p53 and c-erbB-2 oncoprotein were seen in 47% and 22% of gastric adenocarcinoma, respectively. They were not correlated with depth of invasion, lymph node metastasis and Laurens' classification.
Adenocarcinoma* ; Cell Membrane ; Classification ; Cytoplasm ; DNA ; Epithelial Cells ; Genes, Tumor Suppressor ; Lymph Nodes ; Neoplasm Metastasis ; Oncogene Proteins* ; Ploidies ; Prognosis ; Proto-Oncogenes

The prognosis for gastric adenocarcinoma has been found to be related to several factors such as depth of invasion, inflammatory reaction, lymph node metastasis, pathological stage, DNA ploidy, amplification of proto-oncogene, and tumor suppressor gene. This study was performed to investigate the expression rate of p53 protein and c-erbB-2 oncoproteins in gastric adenocarcinoma, and correlation among clinicopathologic parameters, p53 protein and c-erbB-2. The p53 protein and c-erbB-2 oncoproteins were immunohistochemically stained in the tissue specimens of 36 advanced adenocarcinoma and 15 early adenocarcinoma. The results were summarized as follows; 1) Positive reaction for c-erbB-2 oncoprotein revealed an intense brown granular staining predominantly at the tumor cell membrane, with some cell exhibiting a cytoplasmic staining as well. The surrounding mucosal epithelial cells and protein cells around tumors revealed positive reaction. Positive reaction for p53 protein revealed an intense brown granular staining in tumor nuclei. 2) Twenty four of 51 cases(47%) for p53 protein and 11 of 51 cases(22%) for c-erbB-2 oncoprotein of gastric adenocarcinoma revealed positive reaction. 3) There was no significant difference in the expression of p53 protein and c-erbB-2 according to lymph node metastasis, depth of invasion and Laurens' classification. 4) Five of 51 cases(10%) simultaneously revealed c-erbB-2 oncoprotein overexpression associated with p53 protein expression, and 21 of 51 cases(41%) simultaneously revealed negative reaction for c-erbB-2 oncoprotein and p53 protein. There was no correlation between c-erbB-2 oncoprotein overexpression and p53 protein expression. In summary, p53 and c-erbB-2 oncoprotein were seen in 47% and 22% of gastric adenocarcinoma, respectively. They were not correlated with depth of invasion, lymph node metastasis and Laurens' classification.
Adenocarcinoma* ; Cell Membrane ; Classification ; Cytoplasm ; DNA ; Epithelial Cells ; Genes, Tumor Suppressor ; Lymph Nodes ; Neoplasm Metastasis ; Oncogene Proteins* ; Ploidies ; Prognosis ; Proto-Oncogenes

Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). We analyzed 19 patients with lung SCC who underwent surgical treatment between April 2005 and April 2015. Clinical characteristics were reviewed, and DNA was extracted from fresh frozen lung cancer specimens. All of copy number alterations from ArrayCGH were validated using The Cancer Genome Atlas (TCGA) copy number variation (CNV) data of lung SCC. We examined the frequency of copy number changes according to the smoking status (non-smoker [n = 8] or smoker [n = 11]). We identified 16 significantly altered regions from ArrayCGH data, three gain and four loss regions overlapped with the TCGA lung squamous cell carcinoma (LUSC) patients. Within these overlapped significant regions, we detected 15 genes that have been reported in the Cancer Gene census. We also found that the proto-oncogene GAB2 (11q14.1) was significantly amplified in non-smokers patients and vice versa in both ArrayCGH and TCGA data. Immunohistochemical analyses showed that GAB2 protein was relatively upregulated in non-smoker than smoker tissues (37.5% vs. 9.0%, P = 0.007). GAB2 amplification may have an important role in the development of lung SCC in non-smokers. GAB2 may represent a potential biomarker for lung SCC in non-smokers.
Biology ; Carcinoma, Squamous Cell ; Censuses ; Comparative Genomic Hybridization ; DNA ; Epithelial Cells* ; Genes, Neoplasm ; Genome ; Humans ; Incidence ; Lung Neoplasms* ; Lung* ; Neoplasms, Squamous Cell ; Proto-Oncogenes ; Smoke ; Smoking

Female ; Genes, p53 ; immunology ; Humans ; Ovarian Neoplasms ; genetics ; pathology ; Ovary ; pathology ; Proto-Oncogene Proteins ; immunology ; metabolism ; Proto-Oncogene Proteins p21(ras) ; Proto-Oncogenes ; immunology ; Sertoli-Leydig Cell Tumor ; genetics ; pathology ; ras Proteins ; immunology ; metabolism

The present study was carried out to evaluate the correlation of metastasis and prognostic factors in squamous cell carcinoma of head and neck. Examination was performed on a series of thirty-seven patients who were confirmed to squamous cell carcinoma and its lymphatic metastasis by pathologist. Correlations of metastasis and other factors such as angiogenesis, histologic grading, and p53 expression and ras oncogene were studied. The depth of tumors was around 1 to 27mm. Twenty cases were more than 10mm deep, of which seventeen cases were shown lymphatic metastasis. Total score of histologic grading including keratinization, nuclear atypia, growth pattern and intensity of inflammation was ranged from 5 to 10 points. Of these factors, nuclear atypia with intensity of inflammation, and nuclear atypia with growth pattern was correlated with nuclear atypia each. For angiogenesis, number of new-formed vessels were counted 13 to 58 each. Twenty-eight cases were shown to lymphatic metastasis. No correlation with histologic grading and lymphatic metastasis was found. The results of immunohistochemical staining for p53 and ras oncogene revealed that positive cases were 16 and 22, negative for 21 and 15 each. However, both were not correlated with histologic grading and lymphatic metastasis. These results were revealed that angiogenesis was not correlated with lymphatic metastasis of squamous cell carcinoma arising in head and neck. Nuclear atypia with intensity of inflammation and dysplasia with growth pattern were correlated with histologic grading, which suggested that more careful and adequate advice is needed for effective treatment.
Carcinoma, Squamous Cell* ; Genes, ras ; Head* ; Humans ; Inflammation ; Lymphatic Metastasis ; Neck* ; Neoplasm Metastasis*

BACKGROUND: Though K-ras mutation and aberrant p53 have been considered the event of the oncogenesis of pancreatic adenocarcinoma, it is controversial that these have been attributed to difference of survival in pancreatic adenocarcinoma. We investigated for presence of a K-ras mutation, K-ras expression and p53 expression in carcinogenesis of pancreatic adenocarcinoma. Also their correlation with tumor grade, stage and survival was investigated. METHODS: We examined 48 patients surgically resected, formalin-fixed and paraffin-embedded pancreatic adenocarcinoma. By using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), we detected K-ras mutation at codon 12. An aberrant K-ras and p53 expression was stained using an immunohistochemical staining (IHC) method. RESULTS: Thirty-one of 48 cases (64.6%) showed K-ras mutation. K-ras expression was showed in 68.8% (33/48). p53 expression was showed in 47.9% (23/48). There was no correlation between a presence of K-ras mutation or K-ras expression and tumor grade, lymph node metastasis, clinical stage or survival rate. A positive correlation between p53 expression and clinical stage was found (p<0.05). The patients with p53 expression had shorter survival than the patients without p53 expression (p>0.05). CONCLUSION: Mutation of the K-ras gene and aberrant p53 might play an important role in pancreatic carcinogenesis. But mutation of K-ras gene and K-ras expression is not considered to relate to progression of pancreatic carcinoma. It is suggested that p53 expression seems to be associated with a progression of pancreatic carcinoma.
Adenocarcinoma ; Carcinogenesis ; Codon ; Genes, ras ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Pancreatic Neoplasms* ; Prognosis ; Survival Rate

It hae been well established that, specifi alterations in members of the ras gene family, H-ras, K-ras and N-ras, can convert them into active oncogenes. These alterations are either point mutations occurirg in either codon 12, 13 or 61, or alternatively, a 5- to 50-fold amplification of the wfld-type gene. Activated ras oncogenes have been found in a significant proportion of all turnors, but the incidence varies considerably with the tumor type : it is frequent (20~40%) in colarectal eancer and acute myeloid leukemia, but absent or preaent rarely in breast and atomach cancer. But the role of c-K-ras point mutatio in the development of cancers in the female genital tract has not been extensively studied. Polymerase chain reaction followed by gel electrophoresis was performed respectively using wild-type normal and specific point mutation primers{GGT->GAT, GGT->AGT, GGT->TGT and GGT->GTT) to detect, point, mutation of codon 12 of c-K-ras oncogene. The c-K-ras oncogene point mutation was confirmed by Southern blot hybridization using synthetic oligonucleatide probe. 3'-end Iabelled with digoxigenin -dUTP. With this method, the frequency of point mutation on codon 12 of c-K-ras oncogene was examined the tissues in 37 casea of ovarian cancer, 7 cases of endometrial cancer, 36 cases of the gestational trophoblastic tumor, 60 cases of cervical cancer. The relationship between the presence of a c-K-ras point mutation and clinicopathological characteristics of the female genital tract cancers were also analysed. The results were as follows; 1. The incidence of four point mutations on codon 12 of c-K-ras oncogene in 37 ovarian cancers was 45.9% (17/37) and distribution were 43.2% (16/37), 2.7% (1/37) and 0% (0/37) in GGT-->GAT, GGT-->AGT, GGT-->TGT, and GGT-->GTT, respectively. According to histological type, in ovarian cancers, The point mutation of K-ras oncogene waspositive in 45 % (10/22) of serous cystadenocarcinomas. The incidence of four point mutations on codon 12 among 37 patients with ovarian cancer according to histological type was 45.5 % (10/22) with serous cystadenocarcinoma, 57.1% (4/7) of mucinous cystadenocarcinoma. Comparing the positive rate of point mutations of K-ras oncogen among 37 patients with ovarian cancer with the clinical stage, point mutation was detected in 28.5% (2/7) of patients with stage I, 40.0% (2/5) with stage II, and 52.0% (13/25) with stage III/IV. There was no statistically significant increasement of point mutations with the advance of the clinical stage of ovarian cancer. Comparing the positive rate of point mutations of K-ras oncogen among 37 patients with ovarian cancer according to the histologic grade point mutation was detected in 50.0 % (2/4) 0f patients with grade I, 451.7 % (5/12) with grade II and 47.6 % (10/21) with grade III. 2. The incidence of point mutations of K-ras oncogen among 33 patients with ovarian cancer who were performed pelvic lymph node dissection was 57.1 % (12/21) of the patients with pelvic lymph node metastases and 16.7% (2/12) of the patients without pelvic lymph node metastases. There was statistically significant difference between the positive rate of c-K-ras point mutations and the pelvic lymph nodal status(P<0.05). 3. In 7 cases of endometrial cancer, positive rate of K-ras point was 42.8 % (3/7). Point mutations were also detected in 2 cases from 4 choriocarcinomas, but, the point mutation was only detected in 1 case from 60 cervical carcinomas. From these results, we may suggest that the point mutation on codon 12 c-K-ras oncogene are considered to be one of the important genetic change in the tumor formation and progression of ovarian of c-K-ras oncogene seems to be the one stop in the multistep process of tumor formation in ovarian cancer. Furthermore, the point mutation of c-k-ras gene could occur more frequently in the patients of ovarian cancer with pelvic lymph node metastases than in those without pelvic metastases, suggesting the orle in tumor progression. And we concluded that point mutation on codon 12 is comparable frequent in uterine endometrial carcinomas and have significance as an event that contributes to progrssion of endometrial cancers and choriocarcinoma, but cervical carcinoma do not appear to have c-K-ras point mutation in general. More studies will be necessary, but the detection of c-k-ras point mutation as the possibility of biological tumor marker to predict clinical outcome may be utilized in female malignancies.
Blotting, Southern ; Breast ; Choriocarcinoma ; Codon ; Cystadenocarcinoma, Mucinous ; Cystadenocarcinoma, Serous ; Digoxigenin ; Electrophoresis ; Endometrial Neoplasms ; Female* ; Genes, ras ; Humans ; Incidence ; Leukemia, Myeloid, Acute ; Lymph Node Excision ; Lymph Nodes ; Neoplasm Metastasis ; Oncogenes* ; Ovarian Neoplasms ; Point Mutation* ; Polymerase Chain Reaction ; Pregnancy ; Trophoblastic Neoplasms ; Biomarkers, Tumor ; Uterine Cervical Neoplasms