Molecular understanding of lung cancers-A review

Lung cancer is considered to be the most common cancer in the world. The purpose of this paper is to review scientific evidence, particularly epidemiologic evidence of overall lung cancer burden in the world. And molecular understanding of lung cancer at various levels by dominant and suppressor oncogenes.

Molecular understanding of lung cancers-A review

Lung cancer is considered to be the most common cancer in the world. The purpose of this paper is to review scientific evidence, particularly epidemiologic evidence of overall lung cancer burden in the world. And molecular understanding of lung cancer at various levels by dominant and suppressor oncogenes.

Co-expression patterns of Notch1, Snail, and p53 in grade III hepatocellular carcinoma with postoperative recurrence: a preliminary study / 대한간학회지

BACKGROUND/AIMS: We aimed to determine the association between the co-expression patterns of Notch1, Snail, and p53 proteins (NSP) and the postoperative prognosis of hepatocellular carcinoma (HCC). METHODS: The immunoblot data for molecular expression (147 HCC/corresponding non-HCC tissues and 15 dysplastic nodules) and the sequencing data for p53 mutations (110 HCCs) were obtained from our previous study. Data analyses were restricted to cases with HCC differentiation grade III (n=47), due to its high p53 mutation rate. RESULTS: Nineteen of the 47 patients (40.4%) -comprising 12 in the liver and 7 in distant organs-had relapsed at 1-2 years after surgery. There was no relationship between p53 mutation and postoperative recurrence in the grade III HCCs. Seven (87.5%) of the eight relapsed cases with Notch1, Snail, and p53 (wild) co-expression experienced recurrence only within the liver, and all tumors were smaller than 5 cm in diameter. Extrahepatic relapse occurred mostly in HCC patients with tumors larger than 5 cm in diameter, without any deviation in the NSP pattern. CONCLUSIONS: The results of this preliminary study suggest that the co-expression of Notch1, Snail, and p53 (wild) is not inferior to the patterns with p53 mutation as an indicator of postoperative recurrence of grade III HCC.

Analysis of P53 Mutation and Invasion Front Grading in Oral Squamous Cell Carcinomas / 华中科技大学学报（医学）（英德文版）

We examined P53 mutation and invasion front grading(IFG)in 30 cases of oral squamous cell carcinomas(OSCCs).The association of P53 mutation and IFG scores with clinicopathological parameters was evaluated.P53 mutation existed in exon 5-8 in 15 out of the 30 OSCCs(50%).The incidence of P53 mutation was not associated with age,gender,N value and TNM stage.However,there was a significant correlation between P53 mutation and T value(P=-0.046).There were no statistically significant correlations among the clinicopathological parameters and IFG.Interestingly,The IFG score in OSCCs with P53 mutation was significantly higher than that in OSCCs without P53 mutation(P<0.001).These results suggest that the high incidence of P53 mutation is a major mechanism of OSCC carcinogenesis.The presence of P53 mutation indicates the most anaplastic fields in the invasive areas of the tumors,which may predict poor prognosis for the patients.

Frequency of Mutation of Codon 249, Overexpression of p53, and Hepatitis B Virus DNA Positivity in Hepatocellular Carcinoma / 대한임상미생물학회지

BACKGROUND: In hepatocellular carcinoma (HCC), the frequency of p53 mutation and the association with hepatitis B virus (HBV) infection varies with geographic locations and risk factors. The aim of this study was to determine the frequency of codon 249 mutation of p53, p53 overexpression, and HBV DNA positivity and to observe the relationship between them in Korean HCC. METHODS: We analyzed overexpression of p53 in hepatoma tissue from 17 HCC patients by immunohistochemistry (IHC), specific mutations at the third base position of codon 249 by PCR-restriction fragment length polymorphism (PCR-RFLP) method, and presence of HBV by nested PCR. RESULTS: Although a point mutation at codon 250 was seen in one (5.8%) of 17 patients, no codon 249 mutations were found in the patient cohort. The p53 protein was overexpressed in 4 (23.5%) of 17 HCCs. PCR for HBV DNA from HCCs showed a positivity rate of 82.4% (14 of 17 specimens). CONCLUSION: In HCC of this study, HBV infection was not associated with either 249 mutation or overexpression of p53, and overexpression of p53 protein seemed to be related to other than this mutation.

p53 Mutation and p53 Protein Expression in Gastric Cancer Tissues

PURPOSE: Variable changes occur in the progression from normal gastric epithelium to cancer, including many tumor, tumor suppressor and DNA repair genes, as well as growth factor and its receptors. The mutation and protein expression of the p53 gene may be useful prognostic factors, but their significance is still uncertain. METHODS: Specimens from 296 gastric cancer patients, treated by a curative gastrectomy, between March 1999 and April 2001, at Kyungpook National University Hospital, were used. The p53 gene mutation was assessed using a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, and the overexpression of tumor p53 protein using immunohistochemistry. The correlation between the results and clinicopathological parameters were then analyzed. RESULTS: The mutation and protein overexpression of the p53 gene were shown in 61 (20.6%) and 124 (41.9%) tumors, respectively. Of the 61 cases with a p53 mutation, 43 (70.5%) showed overexpression of the p53 protein, and of the 235 without mutation of the p53 gene, 81 (34.5%) had no overexpression of the p53 protein, and also showed statistical significance (P< 0.001). The mutation and protein overexpression of the p53 gene showed no significant differences according to age, gender, stage, location and gross type, but of the 138 intestinal and 128 of the diffuse types, 33 (23.9%) and 18 (14.1%) cases, respectively, showed p53 mutation (P=0.027); whereas, of the 150 well differentiated and 142 poorly differentiated tumors, 75 (50%) and 18 (33.8%), respectively, showed overexpression of the p53 protein. Also, of the 138 intestinal and 128 diffuse types, 71 (51.4%) and 43 (33.6%) showed overexpression of the p53 protein. There were no significant differences in the 5 year survival according to the mutation and protein overexpression of the p53 gene. CONCLUSION: The mutation and protein overexpression of the p53 gene, as assessed by PCR-SSCP and immunohistochemistry, respectively, showed a statistically significant correlation, but had little value as prognostic factors following a curative gastrectomy.

Correlation between High Risk Human Papillomavirus Infection and p53 Protein Overexpression in Adenocarcinoma of Cervix / 대한산부인과학회잡지

OBJECTIVE: The aim of the present study was to analyze the relation between p53 mutation and cervical adenocarcinoma without HPV infection. METHODS: From 1998 to 2002, 54 patients were diagnosed with cervical adenocarcinoma and underwent radical hysterectomy at Seoul National University Hospital. Of them, 50 patients were available for review of medical records and histologic examination. Using ABC method, we performed immunohistochemical staining. If there is 10% or more of staining positive, it was read positive. And we used HPVDNAChip for detection of HPV. RESULTS: Of the 50 patients, 45 (90.0%) patients were positive for high risk HPV and 4 patients (8.0%) were p53 positive. In the patients with negative for p53, there were significantly more patient with HPV positive (p=0.04). Advanced stage of cervical adenocarcinoma was related to high rate of positivity of p53, but it was not statistically significant. CONCLUSION: In patients who diagnosed cervical adenocarcinoma without HPV infection, there were over expression of p53. This suggests that abnormality of p53 may be related to pathogenisis of cervical adenocarcinoma without HPV infection.

p53 Mutation and c-erbB2 Over-expression in Predicting Factor of Responsibility to Neoadjuvant Chemotherapy in Patients with Breast Cancer

PURPOSE: The predictive value of c-erbB2 over-expression, and p53 mutation, to the response rate to neoadjuvant chemotherapy, were assessed in patients with breast cancer. METHODS: Between January 2000 and June 2002, 185 patients, with breast cancer, were put forward for two commonly used chemotherapy regimens prior to surgery. The first 135 received the CMF (cyclophosphamide 600 mg/m2, methotraxate 40 mg/m2, 5-FU 500 mg/m2) regimen, and the remaining 50 the CAF (cyclophosphamide 600 mg/m2, adriamycin 50 mg/m2, 5-FU 500 mg/m2) regimen. The expressions of the estrogen receptor (ER), progesterone receptor (PR), p53 mutation and c-erbB2, were evaluated by immunohistochemistry of needle biopsy samples prior to neoadjuvant chemotherapy. Tumor response was categorized according to the WHO criteria, using the largest diameter in ultrasonography or magnetic resonance imaging. RESULTS: The mean age of the patients in the CMF and CAF groups were 48.8 and 47.4 years. Forty eight (35.6%) and 24 (48.0%) of the patients, in the CMF and CAF groups, respectively, had pathologically partial or complete responses. The tumor size, axillary lymph nodes, lymphatic and vascular invasions, as clinicopathological factors, were significantly correlated with the response to chemotherapy in the CAF group. The absences of ER or PR were also significantly associated with a remission in both the CMF and CAF groups. p53 mutation was not correlated to the response rate of either chemotherapy regimen. There was no significant relationship between the expression of c-erbB2 and the response rate in the CMF group, but a higher percentage of patients with c-erbB2 positive tumors had a response to the CAF regimens. CONCLUSION: p53 mutation is not significantly associated with tumor response, but the over-expression of c-erbB2 can predict the response to the different chemotherapies used in breast cancer.

p53 Gene Mutation, Tumor p53 Protein Overexpression, and Serum Anti-p53 Antibody in Patients with Gastric Cancer

PURPOSE: The clinical implication of p53 mutation in gastric cancer is still unclear, as shown by the discordant results that continue to be reported in the literature. MATENRIALS AND METHODS: To assess p53 gene mutation, tumor p53 overexpression, and serum anti-p53 antibody, we employed a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, an immunohistochemistry using monoclonal antibody DO-7, and an enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Of 169 surgical specimens of gastric cancer, mutation at exon 5~8 of the p53 was identified in 33 (19.5%) and was significantly correlated with lymph node metastasis. Overexpression of p53 was found in 62 specimens (36.7%) and had a significant correlation with tumor differentiation. Serum anti-p53 antibody was positive in 18 patients (10.7%). Twenty-three of the mutated tumors (69.7%) and 39 of the non-mutated tumors (28.7%) displayed immunoreactivity. Twelve of the immunopositive tumors (19.4%) and 6 of the immunonegative tumors produced anti-p53 antibody. These differences were statistically significant (P<0.001 and P=0.005, respectively). There was no significant difference in survival according to the mutation of p53. CONCLUSION: Mutation and overexpression of p53 can be easily detected by immunohistochemistry. However, standardization of the immunohistochemical staining method, as well as guidelines for interpreting the stained result, will produce concordant results and thereby improve clinical application.

Analysis of p53 Gene Mutation in Basal Cell Carcinoma in Korean Patients / 대한피부과학회지

BACKGROUND: There were few data on the gene mutations involved in the development of basal cell carcinoma(BCC) in Korean. OBJECTIVE: To gain insight into the role of p53 gene mutations of BCC in Koreans. METHODS: Fifteen BCCs were screened for mutation of the p53 gene. Immunohistochemical staining was done on the paraffin sections using a labelled streptavidin-biotin-peroxidase complex method with the primary antibody against p53 protein. Analysis of p53 mutation was done by non-isotopic RNase cleavage assay and direct sequencing. RESULTS: Mutation of p53 gene was found in 40%(6/15) of the cases. One case showed mutations in exon 6, one in exon 6 and intron 8, two in exon 8, one in exon 9, and one in intron 5. But ultraviolet specific C->T change was detected in only one case. Immunohistochemical expression of p53 was seen in 40%(6/15), but its expression did not coincide with p53 gene mutation. CONCLUSION: Ultraviolet specific mutations of p53 were much less frequent in Korean than in Caucasian, suggesting other etiologies than ultraviolet radiation.

p53 Mutations in Advanced Supraglottic Cancer / 대한방사선종양학회지

PURPOSE: To determine the prognostic significance of p53 mutations in advanced supraglottic cancer patients. MATERIALS AND METHODS: Twenty-six patients with pertinent tissue materials among 60 patients diagnosed as advanced supraglottic cancer in Kyung Hee university hospital and received total or partial laryngectomy followed by radiation therapy were enrolled. Immunohistochemical staining using DO7 monoclonal antibody was performed. Tumor specimens were analyzed for p53 mutations in exons 5 through 8 by using PCR-SSCP analysis followed by DNA sequencing of all variants. RESULTS: p53 mutations were present in 8 cases among 26 patiets. Mutations within exon 5 were 3 cases, exon 6 were 4 cases, and exon 7 was 1 case. Mean survival time was 70.2 months in patients without mutations, 61.3 months with mutations but there was no statistically significant differences (p=0.596). Mutations were 25% in stage III and 36% in stage IV but there was no statistically significant differences (p=0.563). Mutations were 25% in lymph node negative group and 42% in lymph node positive group but there was no statistically significant differences (p=0.437). CONCLUSION: The presence of a p53 mutation detected by PCR-SSCP is not associated with survival, stage and lymph node status.

Study on the expression and detection of the p53 mutation in Korean colon cancer cell lines

BACKGROUND: Inactivation in p53 tumor suppressor gene through a point mutation and deletion is one of the most frequent genetic changes found in human cancer, with 50% of an incidence. This high rate of mutation mostly suggests that the gene plays a central role in the development of cancer and the mutations detected so far were found in exons 5 to 8. Mutation of p53 locus produced accumulation of abnormal p53 protein, and negative regulation of cell proliferation and transcriptional activation as a suppressor of transformation were lost . In addition, inhibition of its normal cellular function of wild-type by mutant is an important step in tumorigenesis. METHOD: 4 colon cancer cell lines (SNU C1, C2A, C4, C5) were examined for mutation in exons 5 to 8 of the p53 tumor suppressor gene by PCR-SSCP analysis and expression pattern by western blotting and immunoprecipitation. p53-mediated transactivation ability were examined by CAT assay and base substitution of p53 in SNU C2A cell were detected by DNA sequencing. RESULTS: 1) SNU C2A cell and SNU C5 cell were detected mobility shifts each in exon 5 and exon 7 of p53 gene by the PCR-SSCP method, implicating being of p53 mutation. 2) 3 colon cancer cell lines (SNU C1, SNU C2A, SNU C5) expressed wild type and mutant type p53 protein. 3) In northern blot experiment, SNU C2A and SNU C5 cell expressed high level of p53 mRNA. 4) Results of p53-mediated transactivation in colon cancer cell lines by CAT assay represented only SNU C2A cell has transcriptional activity. 5) DNA sequencing in SNU C2A cell showed missense mutation in codon 179 of one allele, histidine to arginine and wild type p53 in the other allele. CONCLUSION: Colon cancer cell lines showed correlation with mutation in p53 gene and accumulation of abnormal p53 protein. Colon cancer cell SNU C2A retained p53-mediated transactivation as heterozygous p53 with one mutant allele in 179 codon and the other wild-type allele.

Angiogenesis and p53 Mutation in Oral and Oropharyngeal Squamous Cell Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: It is well known that microvessel density (MVD) and p53 gene mutation are significantly correlated with tumor behaviors in some types of cancer: however, some studies have reported a lack of relationship among MVD, p53 gene mutation and tumor behavior in oral cancers. The objective of this study was to identify putative association between p53 gene mutation and microvessel density (MVD) and to evaluate the usefulness of this association in deciding the therapeutic plan. MATERIALS AND METHODS: In 25 tumor specimens of oral squarnous cell carcinoma, microvessel density (MVD) was analysed by immunohistorhemical staining with CD-31 monoclonal antibody, and p53 mutation was examined in exon 5 through 8 by PCR-SSCP and sequencing analysis. RESULTS: Seven of the 25 patients had mutation in exon 5 to 8 and all the mutations were missense mutation. The mean of MVD in the mutant group was 13.3+/-2.80 and that of MVD in the wild type group was 18.6+/-1.16. An inverse relationship was seen between MVD and p53 mutation (p=0.047). The p53 gene mutation was frequently found in exon 5. CONCLUSION: MVD and p53 gene mutation were not associated with respect to stage, cervical metastasis and recurrence of' the oral and oropharyngeal cancer. Angiogenesis of oral squamous cell carcinoma might not be regulated by p53, but might be regulated by other factors.

Microsatellite Instability and Overexpression of p53 Protein in Human Gastric Carcinomas: Clinicopathologic Implications and Prognosis

PURPOSE: Striking advances in molecular analysis of human gastrointestinal cancer indicate that malignant transformation of normal epithelial cells is necessary for a multiple process associated with an accumulation of multiple gene abnormalities affecting DNA repair genes, oncogenes, and tumor suppressor genes. Microsatellites are short repeated DNA sequences scattered throughtout the human genome. Microsatellite instability (MSI) may underlie the etiology of mutistep gastric carcinogenesis. The altered microsatellites observed in tumors with DNA replication error (RER) phenotypes may represent the expression of such an instability. METHODS: Fourty-four gastrectomy specimens from patients with gastric carcinomas were examined in an attempt to study the molecular mechanisms of gastric carcinogenesis, to assess the prognostic value of genetic instability and mutant p53 protein expressions, and to evaluate a possible interaction between genetic instability and mutation of the p53 protein. Pairs of tumor and adjacent normal tissue were amplified at six microsatellite loci, and their sizes were compared. Tumors with microsatellite sizes different from their normal tissue sizes for at least two of the tested loci were designated as MSI. Mutations of the p53 protein were investigated with immunohistochemical staining. RESULTS: MSI was detected in 33.3% of the early gastric carcinomas and in 41.4% of the advanced gastric carcinomas with an overall frequency of 38.6%. The frequency of MSI tended to occur more frequently in poorly differentiated adenocarcinomas. The frequency of MSI was not significanctly different with repect to age, sex, size of tumor, location of tumor, depth of invasion,lymph-node metastasis, and Helicobacter pylori infection. Mutation of the p53 protein was detected in 40.0% of the early gastric carcinomas and in 48.3% of the advanced gastric carcinomas with an overall frequency of 45.5%. Mutation of the p53 protein occurred more frequently in positive lymph-node metastasis and advanced stage. There were no correlations between microsatellite instability and p53 expression.The overall 5-year surval rate was 56.6%. The 5-year survival rate of patients with MSI was 58.5%, and that for patient with mutant p53 protein was 42.8%. Gastric cancers with MSI showed a relatively good prognosis, but the result was not statistically significant (p=0.976), and patients with mutant p53 protein had a statistically significant poorer prognosis (p=0.049). CONCLUSION: These findings suggest that both MSI and mutation of the p53 protein are present in early and later stages of malignant transformation. Based on this study, investigations with a larger number of patients are needed to establish their roles as prognostic indicators in gastric cancer.

Prevalence and clinical significance of abnormal p53 gene in patients with ampullary adenocarcinoma / 대한내과학회지

BACKGROUND: Although abnormalities of p53 gene and their relation to clinicopathologic parameters have been identified in some human malignancies, there is little published data on their prevalence and clinical significance in ampullary adenocarcinoma (AAC). The aim of this study is to determine the prevalence of p53 abnormalities in AAC and to evaluate their relation to clinicopathologic features. METHOD:35 formaline-fixed paraffin-embedded tissues of AAC were examined for detection of p53 abnormalities by both single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction- amplified DNA fragments corresponding to exons 5-8 and immunohistochemistry (IHC) using monoclonal antibody to p53 protein (Novocastra, DO7), and the association between the p53 abnormalities and clinicopathologic parameters was analyzed. RESULT: In 22.9% of AAC, p53 gene muation was demonstrated by SSCP analysis, mainly at PCR-amplified exon 8 and exon 7. The p53 protein overexpression by IHC was 48.6% of AAC. Six SSCP and IHC-positive (17.2%) cases and 16 normal (45.7%) cases showed concordant results between the methods, although 13 cases (37.1%) showed discordance, including 11 IHC-positive (31.4%) and 2 SSCP-positive (5.7%) cases. Overall, the prevalence of p53 abnormalities was 54.3%. No significant associations between the p53 abnormalities and clinicopathological parameters such as clinical manifestations, histologic differentiation, and tumor stage were observed. CONCLUSION: The p53 abnormalities detected in 55% of AAC are not associated with prognostic factor, suggesting that abnormal p53 gene may play a role in the development of AAC, but not in its invasiveness.

p53 Mutation and Functional Analyses by Using Yeast Functional Assay / 대한암학회지

PURPOSE: Mutation of the p53 tumor suppressor gene is the most common genetic defect in all human tumors. Because of the widespread mutations and polymorphism in the p53 gene, the conventional screening methods cannot distinguish between polymorphisms or functionally silent mutations and inactivating mutations. It is well known that plasmids can be generated by homologous recombination in vivo in the yeast by cotransforming the PCR product with a linearized yeast expression vector encoding part of a gene and a selectable marker gene. The aim of this study is to develop more easy and reliable method for functional assay of p53 mutation. MATERIALS AND METHODS: We constructed a gap vector which can reliably and conveniently be used to screen p53 mutations in a simple yeast growth assay. The gap vector was constructed as follows: About 100 bp DNA fragments containing parts of N- and C- terminal portion of p53 were cloned into XbaI/SmaI and HindIII/XhoI sites of yeast expressing vector, respectively. The gap vector was obtained by double cutting with SmaI and HindIII followed by gel elution. Yeast was transformed with the reporter vector containing three tandem copies of the consensus p53 binding site by lithium acetate-mediated method. RT-PCR amplification of p53 transcripts from cell lines or tumor tissues was carried out. To investigate whether p53 gene is mutated or not, yeast containing reporter gene was cotransformed with PCR product and linearized gap vector, plated on SD medium minus histidine, and incubated for 3 days. The colonies on selective media were isolated and characterized. RESULTS: The tumor tissues examined were one hepatocellular carcinoma, three breast cancers, two stomach cancers and two colon cancers. One hepatocellular carcinoma tissue had mutation in both alleles of the p53 gene, and 7 cancer tissues had heterozygous mutations in the p53 gene. The result of functional assay was well correlated with mutational analysis by sequencing. CONCLUSION: p53 functional assay system might be easy and reliable method for functional screening of p53 on tumor tissues and this might be used for screening of other mutated gene. This technique, FASAY, requires only a few steps, can be automated readily and should permit screening for germline or somatic heterozygous mutations in any gene whose function can be monitored in yeast.

Mutation of The p53 Gene in Acute Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: A p53 gene is one of the member of tumor suppressor genes involved in the control of cell cycle. The alteration of the p53 gene induces uncontrolled cellular proliferation leading to the development of tumor. Mutations of the p53 gene were found in various human cancers including hematologic malignancies. The incidence of the p53 mutation in acute myelogenous leukemia was reported to be relatively low, however, there has been no report as to the incidence and the characteristics of the p53 mutation in acute myelogenous leukemia in Korea. METHODS: Polymerase chain reaction and single strand conformational polymorphism(PCR-SSCP) was done to screen abnormal band shifts in exons 5, 6, 7, 8 of p53 gene in myeloid blasts obtained from bone marrow aspirates at the time of diagnosis from patients with de novo acute myelogenous leukemia. Mutation of the p53 gene was confirmed by direct sequencing with Sanger method in the DNAs with abnormal band shifts. Cytogenetic analysis of the bone marrow was performed by G-banding method. RESULTS: Only 1(2%) out of 48 patients with acute myelogenous leukemia showed abnormal band shift in exon 5 with PCR-SSCP. Base sequence of exon 5 of this patient with normal karyotype was found to have silent mutation at codon 143 from GTG(valine) to GTA(valine). He had acute myelogenous leukemia of M6 subtype and the leukemia was refractory to two cycles of standard induction chemotherapy, succumbed to death at last. CONCLUSION: Mutation of the p53 gene was found to be very rare in acute myelogenous leukemia in Korea and it was thought to be involved in leukemogensis only in some patients.

Expression of CD44V6 and p53 gene mutation in human ovarian carcinoma / 中国癌症杂志

Purpose:To investigate p53 gene mutation, CD44V6 expression and their relationship with metastasis of ovarian carcinoma in tumor diagnosis. Methods:PCR SSCP with silver staining was used to detect the mutation of p53 gene; by using Southern blot and image analysis, the quantitative and qualitative expression of CD44V6 were also determined. Results:The positive percentage of CD44V6 expression and p53 gene mutation was not detectable in any of the normal ovarian specimens but in the benign tumors, non metastasizing and metastasizing carcinomas it was 10%, 75%, 88% and 5%, 40%, 60% respectively. The mean dark density of each band in these four groups(mentioned above) was 85.25?23.16, 817.11?126.5, 3820.14?289.43 and 10132.92?1521.20 respectively. The expression of CD44V6 of metastasizing carcinomas was higher than that of non metastasizing group. Conclusions:The expression of CD44V6 is related to tumor metastasis; the positive percentage of CD44V6 is higher than that of p53 gene mutation in the group of metastasizing and non metastasizing tumors; Compared to p53 gene mutation, CD44V6 is a better marker for tumor metastasis.

p53 Mutation Patterns in Primary Head and Neck Squamous Cell Carcinomas and Their Metastatic Neck Nodes / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Analysis of molecular events that occur during the evolution of head and neck squamous cell carcinoma has discovered multiple genetic changes, such as chromosomal abnormalities, activation of oncogenes, and inactivation of tumor suppressor genes. The involvement of p53 gene at the advanced tumor stage including lymph node metastasis has been demonstrated in head and neck cancers. Although there is some evidences for the persistence of p53 mutation of lymph node metastasis in head and neck cancer, no systematic study has been carried out to elucidate the persistence of p53 mutations and together with intratumoral heterogeneity of p53 mutations in primary and metastatic head and neck cancers. The purpose of this study was to reveal the pattern and intratumoral heterogeneity of p53 mutations in primary head and neck squamous cell carcinomas and their metastatic lymph node. MATERIALS AND METHODS: In total 71 microdissected samples of primary tumors and their metastatic lymph nodes from 12 head and neck squamous cell carcinomas, exon 5 to 8 of p53 tumor supressor gene were analyzed by single strand conformational polymorphism and immunohistochemical study for the specimens. RESULTS: In eight of 12 cases, mutational inactivations were identified. Involved exons were five cases of exon 5, two cases of exon 8 and one case of exon 7. In all of eight cases, mutations were identical in the primary and all of its metastatic samples. In microdissected study to obtain tumoral clones, mutation of p53 showed identical kind of p53 mutation for both primary and metastatic samples. CONCLUSION: p53 mutations of primary and metaststic head and neck squamous cell carcinomas showed identical kind of p53 mutation with intratumoral heterogeneity.

Distinct Mutation of p53 Gene in Bladder Cancer of Smoking and Nonsmoking Patients / 대한비뇨기과학회지

PURPOSE: It is well known that smoking is one of the most important etiologic factor in bladder cancer and mutations of p53 tumor suppressor gene are the important step in carcinogenesis of urinary bladder. In this study, we investigated the difference in pattern and rate of p53 gene mutation between smoker and non-smoker MATERIALS AND METHODS: Of 26 bladder transitional cell carcinoma, 16 cases were smoker and 10 cases were non-smoker. We evaluated mutation of the p53 gene concentrated on axon 5 through 8, using polymerase chain reaction- single strand conformation polymorphism(PCR-SSCP) with radioisotope. RESULTS: 3 cases(18.7%) of 16 smoker were found to have p53 gene mutation, but none of 10 non-smoker was found. 2 of 3 cases of p53 gene mutation were found in exon 5 and 1 in exon 7. The pattern of p53 gene mutation was different in 3 cases. CONCLUSIONS: Although the more cases will be needed in this study, we think that a mutation of p53 in bladder cancer may be associated with cigarette smoking.