Possible mechanism and significance of rare p53 mutation in Epstein-Barr virus-associated gastric cancer / 中国肿瘤临床

In 2014, The Cancer Genome Atlas firstly classified gastric cancer into four types according to genotype. Epstein-Barr virus (EBV) positive gastric cancer or EBV-associated gastric cancer (EBVaGC) is attracting attention because it is a possibly suitable group for immunotherapy. Among the mutations observed in tumors, such as gastric cancer, p53 mutations are the most frequent. In particular, it occurs more frequently in EBVaGC than in EBV-negative gastric cancer (EBVnGC). Meanwhile, EBV infection is considered as an early event of tumorigenesis. The interactions between wild-type p53 proteins and BZLF1 (Z) proteins are essential in maintaining the latent state of EBV infection and promoting early replication. In the latter stages of replication, wild-type p53 proteins are degraded through the ubiquitination of some viral molecules. These findings may indicate the importance of wild-type p53 genes in EBVaGC formation. Inflammatory responses induced by EBV infection, tumor with a large number of lymphocyte infiltration, genome high mutation, and PD-L1 amplification make it possible to become the appropriate group of immunotherapy, which also illustrate that the important role of immune microenvironment during tumor progression. In EBVnGC, extremely high levels of p53 mutation were observed because of several associated factors, and the p53 protein encoded by the mutant p53 gene lost its antitumor function after tumorigenesis. In this review, the possible mechanisms of rare p53 mutation in EBVaGC are summarized.

Characterization and Prognostic Value of Mutations in Exons 5 and 6 of the p53 Gene in Patients with Colorectal Cancers in Central Iran

BACKGROUND/AIMS: We aimed to investigate the relation-ships among various mutations of the p53 gene and their protein products, histological characteristics, and disease prognosis of primary colorectal cancer in Isfahan, central Iran. METHODS: Sixty-one patients with colorectal adenocarcinoma were enrolled in the study. Mutations of the p53 gene were detected by single-stranded conformation polymorphism and DNA sequencing. The protein stability was evaluated by immunohistochemistry. Patients were followed up to 48 months. RESULTS: Twenty-one point mutations in exons 5 and 6 were detected in the tumor specimens of 14 patients (23%). Of those, 81% and 9.5% were missense and nonsense mutations, respectively. There were also two novel mutations in the intronic region between exons 5 and 6. In 11 mutated specimens, protein stability and protein accumulation were identified. There was a relationship between the type of mutation and protein accumulation in exons 5 and 6 of the p53 gene. The presence of the mutation was associated with an advanced stage of cancer (trend, p<0.009). Patients with mutated p53 genes had significantly lower survival rates than those with wild type p53 genes (p<0.01). CONCLUSIONS: Mutations in exons 5 and 6 of the p53 gene are common genetic alterations in colorectal adenocarcinoma in central Iran and are associated with a poor prognosis of the disease.

Lung cancer andCYP1A1 orGSTM1 polymorphisms

Most chemical carcinogens are metabolized and activated in vivo by phase I enzymes including the microsomal cytochromes P450 and epoxide hydroxylases. The carcinogens and their metabolites are detoxified by phase II enzymes that in clude various transferases such as glutathion-S-transferases (GST). Increasing numbers of studies have demonstrated the association of the polymorphisms inGSTM1 (a member of GST) andCYP1A1 genes with the susceptibility to lung cancer. Subsequently, the polymorphisms appear to be important biomarkers that provide information for assessment of exposure and total burden of environmental carcinogens. Therefore, the investigation of the polymorphisms in these genes will provide information not only for the prediction of individual cancer risk but also for the prevention of cancer. In this review, we will summarize the polymorphisms in theGSTM1 andCYP1A1 genes and their relation to lung cancer susceptibility.

Comparative Study of p53 Mutation and Oncoprotein Expression in Gastric Adenocarcinoma

PURPOSE: The p53 tumor suppressor gene is believed to play a pivotal role in preventing the uncontrolled cellular growth characteristic of cancer. Mutation of the p53 gene represent one of the most common genetic alterations in human cancers, and the acquisition of such defects is strongly associated with tumor progression and metastasis. The aim of this study was to evaluate the relation between p53 immunoreactivity and the mutation of p53 gene in gastric adenocarcinoma obtained by laser capture microscope. MATENRIALS AND METHODS: Formalin fixed paraffin embedded tissue specimens were obtained from 20 patients who underwent surgery for gastric cancer. According to UICC TNM system, 3 of the cases were Ia, 2 cases II, 4 cases IIIa, 5 cases IIIb, and 6 cases IV. RESULTS: Immunohistochemical staining revealed eight cases as negative (less than 10%), twelve cases as postive (more than 10%). The locations of mutations were as follows; 7 cases had point mutation at exon 4, and 3 cases point mutation at exon 8. There was no mutation at exon 5, 6, 7 and 9. The mutation was observed in 1 case out of 8 p53 oncoprotein negative cases, and 7 cases out of 12 p53 positive cases. The mutation was more common in p53 positive cases (P<0.05), However, there was no significant correlation between p53 mutation observed by DNA sequencing after laser capture microdissection and expression of p53 oncoprotein. CONCLUSION: These result suggest that he expression of p53 oncoprotein not to be related to the mutation of p53 gene at exons 4 through 9 in gastric cancer.

Comparative Study of p53 Mutation and Oncoprotein Expression in Gastric Adenocarcinoma

PURPOSE: The p53 tumor suppressor gene is believed to play a pivotal role in preventing the uncontrolled cellular growth characteristic of cancer. Mutation of the p53 gene represent one of the most common genetic alterations in human cancers, and the acquisition of such defects is strongly associated with tumor progression and metastasis. The aim of this study was to evaluate the relation between p53 immunoreactivity and the mutation of p53 gene in gastric adenocarcinoma obtained by laser capture microscope. MATENRIALS AND METHODS: Formalin fixed paraffin embedded tissue specimens were obtained from 20 patients who underwent surgery for gastric cancer. According to UICC TNM system, 3 of the cases were Ia, 2 cases II, 4 cases IIIa, 5 cases IIIb, and 6 cases IV. RESULTS: Immunohistochemical staining revealed eight cases as negative (less than 10%), twelve cases as postive (more than 10%). The locations of mutations were as follows; 7 cases had point mutation at exon 4, and 3 cases point mutation at exon 8. There was no mutation at exon 5, 6, 7 and 9. The mutation was observed in 1 case out of 8 p53 oncoprotein negative cases, and 7 cases out of 12 p53 positive cases. The mutation was more common in p53 positive cases (P<0.05), However, there was no significant correlation between p53 mutation observed by DNA sequencing after laser capture microdissection and expression of p53 oncoprotein. CONCLUSION: These result suggest that he expression of p53 oncoprotein not to be related to the mutation of p53 gene at exons 4 through 9 in gastric cancer.

Lung Cancer and \it{CYP1A1} or \it{GSTM1} Polymorphisms

Most chemical carcinogens are metabolized and activated in vivo by phase I enzymes including the microsomal cytochromes P450 and epoxide hydroxylases. The carcinogens and their metabolites are detoxified by phase II enzymes that include various transferases such as glutathion-S-transferases (GST). Increasing numbers of studies have demonstrated the association of the polymorphisms in GSTM1 (a member of GST) and CYP1A1 genes with the susceptibility to lung cancer. Subsequently, the polymorphisms appear to be important biomarkers that provide information for assessment of exposure and total burden of environmental carcinogens. Therefore, the investigation of the polymorphisms in these genes will provide information not only for the prediction of individual cancer risk but also for the prevention of cancer. In this review, we will summarize the polymorphisms in the GSTM1 and CYP1A1 genes and their relation to lung cancer susceptibility.

Mutations of p53 Tumor Suppressor Gene in Spontaneous Canine Mammary Tumors

Mutation of the p53 tumor suppressor gene has been related in the pathogenesis of numerous human and canine cancers, including breast cancers and mammary tumors. We have investigated exons 5-8 of the p53 gene for mutations in 20 spontaneous canine mammary tumors using polymerase chain reaction (PCR) with direct sequence analysis to evaluate the role of this gene in canine mammary tumorigenesis and analyzed to compare with other clinicopathological parameters including age, histology, stage, recurrence and death from tumor. Four missense (one case had two missense mutations) and one nonsense mutations were detected in 10 malignant lesions (40%), and two missense and one silent mutations were found in 10 benign mammary tumors (30%). Five of the missense mutations were located in highly conserved domains II, III, IV and V. After a follow-up period, four dogs showed a progression and three of these patients revealed death from mammary carcinoma with p53 mutation. These results demonstrated that the p53 gene mutations might be involved in the development of canine mammary tumors and contribute to the prognostic status in canine mammary carcinomas.

Correlation between p53 and MIB1 Index Expression of Primary Tumor and Metastatic Lymph Node in Breast Cancer / 한국유방암학회지

PURPOSE: This study was designed to elucidate the biology of cancer metastasis and differences in the biologic status between primary tumors and metastatic lymph nodes of invasive breast cancer by comparing the well known prognostic factors p53 gene mutation, p53 protein expression and the MIB-1 index. An additional goal was to investigate the p53 mutational pattern of breast cancer patients. METHODS: We used the PCR-SSCP method to detect p53 gene mutation and immunohistochemical staining to establish p53 protein expression and the MIB-1 labelling index in 25 primary tumors and metastatic lymph nodes from breast cancer patients. We then made a comparison the between primary tumors and the metastatic lymph nodes. RESULTS: The results indicated a correlation between histologic grade and p53 gene mutation as well as p53 protein expression, but showed no correlation to MIB-1 labelling index. The concordance rates of p53 gene mutation and p53 protein expression between the primary tumors and metastatic lymph nodes were 72% and 100%, respectively.Three cases showed a different mutated exon number between the primary tumors and the metastatic lymph nodes. Some cases showed p53 gene mutation only in the primary tumors, but while other cases only in the metastatic lymph nodes. The MIB-1 labelling index increased with tumor grade. The p53 altered group show a higher mean MIB-1 index than the non altered group's in both the primary tumors and metastatic lymph nodes. CONCLUSION: p53 gene mutation is not consistent with p53 protein expression and there are some differences in p53 gene mutation between primary tumors and metastatic lymph nodes in breast cancer. Therefore, metastatic tumor have different characteristics from those of primary tumors. In breast cancer, metastasis is regulated not only by an up- regulating mechanism but also by a down-regulating mechanism.

Correlation between p53 and MIB1 Index Expression of Primary Tumor and Metastatic Lymph Node in Breast Cancer / 한국유방암학회지

PURPOSE: This study was designed to elucidate the biology of cancer metastasis and differences in the biologic status between primary tumors and metastatic lymph nodes of invasive breast cancer by comparing the well known prognostic factors p53 gene mutation, p53 protein expression and the MIB-1 index. An additional goal was to investigate the p53 mutational pattern of breast cancer patients. METHODS: We used the PCR-SSCP method to detect p53 gene mutation and immunohistochemical staining to establish p53 protein expression and the MIB-1 labelling index in 25 primary tumors and metastatic lymph nodes from breast cancer patients. We then made a comparison the between primary tumors and the metastatic lymph nodes. RESULTS: The results indicated a correlation between histologic grade and p53 gene mutation as well as p53 protein expression, but showed no correlation to MIB-1 labelling index. The concordance rates of p53 gene mutation and p53 protein expression between the primary tumors and metastatic lymph nodes were 72% and 100%, respectively.Three cases showed a different mutated exon number between the primary tumors and the metastatic lymph nodes. Some cases showed p53 gene mutation only in the primary tumors, but while other cases only in the metastatic lymph nodes. The MIB-1 labelling index increased with tumor grade. The p53 altered group show a higher mean MIB-1 index than the non altered group's in both the primary tumors and metastatic lymph nodes. CONCLUSION: p53 gene mutation is not consistent with p53 protein expression and there are some differences in p53 gene mutation between primary tumors and metastatic lymph nodes in breast cancer. Therefore, metastatic tumor have different characteristics from those of primary tumors. In breast cancer, metastasis is regulated not only by an up- regulating mechanism but also by a down-regulating mechanism.

Correlation between p53 and MIB1 Index Expression of Primary Tumor and Metastatic Lymph Node in Breast Cancer

PURPOSE: This study was designed to elucidate the biology of cancer metastasis and differences in the biologic status between primary tumors and metastatic lymph nodes of invasive breast cancer by comparing the well known prognostic factors p53 gene mutation, p53 protein expression and the MIB-1 index. An additional goal was to investigate the p53 mutational pattern of breast cancer patients. METHODS: We used the PCR-SSCP method to detect p53 gene mutation and immunohistochemical staining to establish p53 protein expression and the MIB-1 labelling index in 25 primary tumors and metastatic lymph nodes from breast cancer patients. We then made a comparison the between primary tumors and the metastatic lymph nodes. RESULTS: The results indicated a correlation between histologic grade and p53 gene mutation as well as p53 protein expression, but showed no correlation to MIB-1 labelling index. The concordance rates of p53 gene mutation and p53 protein expression between the primary tumors and metastatic lymph nodes were 72% and 100%, respectively. Three cases showed a different mutated exon number between the primary tumors and the metastatic lymph nodes. Some cases showed p53 gene mutation only in the primary tumors, but while other cases only in the metastatic lymph nodes. The MIB-1 labelling index increased with tumor grade. The p53 altered group show a higher mean MIB-1 index than the non altered group's in both the primary tumors and metastatic lymph nodes. CONCLUSION: p53 gene mutation is not consistent with p53 protein expression and there are some differences in p53 gene mutation between primary tumors and metastatic lymph nodes in breast cancer. Therefore, metastatic tumor have different characteristics from those of primary tumors. In breast cancer, metastasis is regulated not only by an up-regulating mechanism but also by a down-regulating mechanism.

p53 Gene Mutation in Epithelial Ovarian Cancer / 대한산부인과학회잡지

OBJECTIVE: Although ovarian cancer is the leading cause of death among all cancers of the female reproductive tract, the genetic alterations involved in ovarian cancer remains largely unknown. Recently, mutations of the p53 gene have been documented in many types of human cancer including ovarian cancer. METHODS: In tbe present study, p53 gene mutation was examined in DNA samples extracted from paraffin embedded surgical specimens of ovarian cancer. Furthermore, clinicopathological parameters were examined in relation to p53 gene mutation in order to understand the role of p53 mutation in the development of ovarian cancer. Using the polymerase chain reaction(PCR) and single strand conformational polymarphism(PCR-SSCP), p53 gene mutation was examined and the mutations were confirmed by DNA scquencing in 17 cases of ovarian cancer. RESULTS: Abnormal bands indicating mutation were detected in 2/17(11.8%). DNA sequencing confirmed in 2 mutations and revealed C to T and A to T nucleotide chmges. In clinicopathological parameters, FIGO stage, grade, and recunence were not correlated with the p53 gene mutation. However, the recurrence rate was higher in patients with mutant p53 compared with those with wild type p53(50.0% vs 13.3%), altbough this is not statisticaUy significant. CONCLUSION: In conclusion, p53 gene mutation shows no correlation with stage, grade and recurrence, and p53 gene mutation does not appear to be a marker that predicts the biological behavior or the outmme of the disease. This study suggested useful data to elucidate the mechanism of chemotherapy-resistant ovarian cancer and further p53 expression assay would be mandatory for p53 nonfunctioning ovarian cancas.

Sequencing of p53 Gene Mutations in Primary Breast Cancer Tissues / 대한암학회지

PURPOSE: The etiology of breast cancer involves very complex factors such as genetic, hormonal, and dietary. The peak age of Korean breast cancer is much earlier, about ten years, than those of western countries. The role of p53 gene on the carcinogenesis has been studied since 1991. This study was designed for the evaluation of genetic factor by determining p53 gene mutations in Korean breast cancer. MATERIALS AND METHODS: Mutation screening on p53 tumor suppressor gene was examined with PCR-SSCP and nucleotide sequencing technique from the genomic DNA extracted from the 27 fresh-frozen breast cancer tissues. RESULTS: Mutations in p53 gene exon 5-7 were identified in 2 of 27 cases (7%). One had a missense mutation substituted gcg with ggg at codon 159, exon 5, and the other had a point mutation substituted tcc serine to tGc cysteine at codon 241, exon 7. CONCLUSION: Point mutation of p53 gene in breast cancer seems to be the major defect found in Korean patients. It is necessary to perform further study in mutation of other exon 2, 4, 8, 9, and 11 of p53 gene to compare the genetic backgrounds of Korean breast cancer with those of westerns.

Study of p53 Mutation and Protein Expression in HPV Typed Uterine Cervical Cancer / 대한산부인과학회잡지

Oncogenic human papillomavirus(HPV) infection has been implicated in the pathogenesis of cervical carcinoma. The HPV E6 and E7 oncoproteins are thought to play a crucial role in this process by their interactions with the p53 protein and the retinoblastoma suceptibility gene products respectively. The E6 protein binds to and stimulates the degradation of the p53 protein and mutations involving evolutionary conserved regions of the p53 gene also can alter p53 function, so both HPV E6 protein and p53 mutation may play a role in the carcinogenesis of cervical carcinoma. The purposes of this study are to examine the role of p53 gene in relation to the presence of HPV DNA in primary cervical carcinoma and to assess the prognostic value of the p53 gene and HPV infection in surgically treated cervical carcinoma. Formalin fixed, paraffin embeded blocks of 73 cervical carcinomas were evaluated for the status of oncogenic HPV infection by in situ hybridization, and the p53 overexpression by immunohistochemical staining. 43 cases out of 73 cervical carcinomas were evaluated for the HPV type by polymerase chain reaction (PCR)-Southern blot analysis, and the presence of mutations involving exon 4-10 of the p53 gene was examined by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP), and then, confirmed by direct DNA sequencing. 48 cases of 73 cervical carcinomas showed oncogenic HPV DNA by in situ hybridization and 22 cases showed p53 overexpression by immuno-histochemical staining. There was inverse correlationship between HPV infection and p53 overexpression(p=0.03). HPV infection and p53 overexpression were not significantly correlated with clinicopathological parameters such as age, FIGO stage, histologic type, tumor size, lymph node metastasis, depth of invasion, and tumor differentiation. 32 cases of 43 cervical carcinomas showed oncogenic HPV DNA by PCR-Southern blot analysis. 30 cases(69.8%) of 43 cervical carcinomas showed HPV 16 DNA and 9 cases(20.9%) showed HPV 18 DNA and 11 cases(25.6%) showed no HPV 16/18 DNA. 8 cases of 43 cervical carcinomas showed p53 gene mutation in PCR-SSCP analysis. 7 cases of 8 mutations showed positive p53 overexpression and another 1 case showed negative p53 overexpression. 4 cases of 8 mutations had no HPV 16/18 infection and another 4 cases had HPV 16 and/or 18 infection. There was no significant correlation between p53 mutation and HPV infection. In 8 cases showing mutation, 4 cases showed point mutation, 3 cases showed frame shift mutation, and another 1 case showed deletion from codon 125 to 132. p53 mutations were located at exon 4, 5, 6, 7, and 8, highly conserved region. Oncogenic HPV DNA can be identified in most cervical carcinomas, and mutations involving highly conserved regions of p53 gene, although infrequent in cervical cancer, occur preferentially in tumors without HPV infection but indenpendently. Although HPV infection and p53 overexpression shows no prognostic values in our study, further investigation is required for clarifyng its prognostic value in gynecologic malignancies.

p53 Gene Mutations in Transitional Cell Carcinoma of the Renal Pelvis / 대한비뇨기과학회지

Inactivation or loss of suppressor genes on a specific chromosome plays an important role in the development and progression of cancer. Recent studies have shown that p53 gene acts as a tumor suppressor gene and that its mutation appears to be related to the aggressiveness of transitional cell carcinoma of the bladder. To investigate the significance of p53 gene mutations in transitional cell carcinoma of the renal pelvis (renal pelvis tumor), 28 tumors with various stages and grades were examined for p53 gene mutations in exon regions 5 to 8 using polymerase chain reaction single-strand conformation polymorphism analysis. Seven (25%) of 28 pelvis tumors were found to have p53 gene mutations. Three of 12 superficial tumors including pTis, pTa, and pT1 were found to have p53 gene mutations. And only four of 16 invasive tumors with pT2, pT3, and pT4 were found to have p53 mutations. In the respect of tumor grade, p53 gene mutation was found in four of the 14 tumors with grade I and II, while three of 14 tumors with grade III, and IV were found to have p53 gene mutations. These observations suggest that, in contrast to bladder cancer, the incidence of p53 gene mutations does not related to the tumor stages and grades in transitional cell carcinoma of the renal pelvis. These results further indicate that p53 gene mutation may not represent a genetic marker of malignant potentials in transitional cell carcinoma of the renal pelvis.

The Prognostic significance of p53 Gene Mutation and DNA Ploidy and Their Correlation in Advanced Epithelial Ovariasn Canser / 대한산부인과학회잡지

Ovarian cancer has a higher mortality rate than any other gynecologic malignancy and the majority of the patients are in an advanced stage at the time of diagnosis. However, well-estagblished clinicopahtological prognostic factiors such as stage, hisgologic type, grade of differentiation, amonut of residual tumor, and age are insufficient for prediction survival, thus necessitating new, more objective, and reproducible biological prognostic varialbes. Mutation of p 53 tumor suppressor gene and DNA aneuploidy are known to be associated with development and progression of ovarian cancer, but their prognostic sinificance is not yet conclusive. The objectives of this study were to define the nature and the prevalence of p53 gene mutation and DNA aneuploidy, and to deteirmine thier prognostic implications and their correlation in advanced epithelial ovarian cancer. the study population implications and of p53 tumor suppressor gene and DNA anuuploidy, and to determine their prognostic implications and their correlation in advanced epithelial ovarian cancer. The study population comprised tiryty-two patients with stage II to IV epithelial ovarian cancer who were mangaged at Asan Medical Center between may 1993 and April 1996. Fresh frozen tumor samples of primary lesion were analysed by direct DNA sequencing technique using ploymerase chain reaction with primers for exon 5,6,7 and 8. Measurerements of the nuclear DNA content were performed on the same cytometry. Twelve (37.5%) point mutations were identified in all exons, 3,2,2and 5 cases in exon 5,6,7and 8 of p 53 gene respectively without any preferential pattern of nucleotide substitution. Twenty-Three (71.9%) cased of tumors were revealed to be aneuploid (DNA index > 1.05). there was no correlation between p53 gene mutation and DNA ploidy. The presence or absence of p53 gene mutation had no signficant correlation with FIGO stge, histologic grade, serum CA 125 level after second chemotherapy and residual tumor size after debulking surgery. Two-year survival rates of patients with and with out mutation showed no difference. On the other hand, patients with aneuploid tumors revealed to be significantly associated with more advanced stage (P=0.46) and higher level of serum CA 125 after second chemotherapy (P=0.18) and had shorter 2-year survival rate than shose with diploid tumor, although the statistical significance was marginal (P=0.057). In conclusion, p53 gene mutation and DNA ploidy show no correlation, and p53 gene mutation does not appear to be a marker prediction the biological behavior or the outcome of the disease. However, DNA ploidy was shown to be utilized as a prognostic fatoc for survival in advanced epithelial ovarian cnacer, althour further studies for longer period of time are required to confirm.

The Prognostic significance of p53 Gene Mutation and DNA Ploidy and Their Correlation in Advanced Epithelial Ovariasn Canser / 대한산부인과학회잡지

Ovarian cancer has a higher mortality rate than any other gynecologic malignancy and the majority of the patients are in an advanced stage at the time of diagnosis. However, well-estagblished clinicopahtological prognostic factiors such as stage, hisgologic type, grade of differentiation, amonut of residual tumor, and age are insufficient for prediction survival, thus necessitating new, more objective, and reproducible biological prognostic varialbes. Mutation of p 53 tumor suppressor gene and DNA aneuploidy are known to be associated with development and progression of ovarian cancer, but their prognostic sinificance is not yet conclusive. The objectives of this study were to define the nature and the prevalence of p53 gene mutation and DNA aneuploidy, and to deteirmine thier prognostic implications and their correlation in advanced epithelial ovarian cancer. the study population implications and of p53 tumor suppressor gene and DNA anuuploidy, and to determine their prognostic implications and their correlation in advanced epithelial ovarian cancer. The study population comprised tiryty-two patients with stage II to IV epithelial ovarian cancer who were mangaged at Asan Medical Center between may 1993 and April 1996. Fresh frozen tumor samples of primary lesion were analysed by direct DNA sequencing technique using ploymerase chain reaction with primers for exon 5,6,7 and 8. Measurerements of the nuclear DNA content were performed on the same cytometry. Twelve (37.5%) point mutations were identified in all exons, 3,2,2and 5 cases in exon 5,6,7and 8 of p 53 gene respectively without any preferential pattern of nucleotide substitution. Twenty-Three (71.9%) cased of tumors were revealed to be aneuploid (DNA index > 1.05). there was no correlation between p53 gene mutation and DNA ploidy. The presence or absence of p53 gene mutation had no signficant correlation with FIGO stge, histologic grade, serum CA 125 level after second chemotherapy and residual tumor size after debulking surgery. Two-year survival rates of patients with and with out mutation showed no difference. On the other hand, patients with aneuploid tumors revealed to be significantly associated with more advanced stage (P=0.46) and higher level of serum CA 125 after second chemotherapy (P=0.18) and had shorter 2-year survival rate than shose with diploid tumor, although the statistical significance was marginal (P=0.057). In conclusion, p53 gene mutation and DNA ploidy show no correlation, and p53 gene mutation does not appear to be a marker prediction the biological behavior or the outcome of the disease. However, DNA ploidy was shown to be utilized as a prognostic fatoc for survival in advanced epithelial ovarian cnacer, althour further studies for longer period of time are required to confirm.

ABNORMAL CHANGE OF p53 GENE IN GASTRIC CANCER AND PRECANCER- OUS LESIONS AND APC GENE IN GASTRIC CARCINOMA AND NEAR TISSUES / 中华消化内镜杂志

p53 gene mutation (exon4 , 5 , 6 . 7 . 8 and intron6) in gastric cancer and precancerous le- sions and p53 gene (exon4 and intron6) .APC gene deletion in gastric carcinomas were studied by PCR/ SSCP and PCR/RFLP. Results showed: mutation rate of p53 in intestinal metaplasia ,dysplasia and gas- tric carcinoma was 37. 5% (3/8) ,42. 1 % (8/19) , 53. 3% (16/30) ,respectively. There was significant dif- ference between groups of metaplasia、dysplasia、cancer and that of normal control. We found there were no exon8 mutation in metaplasia and dysplasia , but 4 cases in cancer group. lt is suggestted that exon8 mutation occurs at the late stage of gastric cancer , but exon 5 , 6 , 7 mutation occur in the course of pre- cancerous lesions to cancer. Loss of heterozygosity (LOH) of exon4 . intron6 . APC was 47. 4 % ( 9/19) . 8. 7%C2/23).16. 7%(3/18) ,respectively. There are some relationship between LOH of exon4 and poor- ly differentiation , lymph node metastas , depth of invasion. LOH of exon4 may be one of prognostic marker of gastric cancer. We concluded that p53 gene mutation is an early event and perhaps has syner- gism with ras oncogene in gastric carcinogenesis

p53 Gene Mutations in Bladder Cancer (II): Mutation Analysis by Non-isotopic SSCP Method / 대한비뇨기과학회지

Background. p53 gene mutations are known to be an important prognostic factor in bladder cancer. Single strand conformation polymorphism (SSCP) analysis has been suggested to be a promising method to detect p53 gene mutation. However, the technical pitfalls associated with conventional SSCP using radioisotope precluded its wide application in clinical practice. We herein have tried non-isotopic SSCP and analyzed the value of this, new method for detecting mutation of p53 gene in bladder cancer. Methods. In this study of 32 bladder transitional cell carcinoma, we comparatively analyzed polymerase chain reaction (PCR) of exons 5 to 8 of p53 gene, followed by 1) conventional, isotopic-SSCP analysis, 2) non-isotopic SSCP analysis, and 3) DNA sequencing analysis. Results. On isotopic SSCP analysis, 9 out of 32 cases (28.1%) showed mobility shifts. On non-isotopic SSCP analysis, 10 cases (31.0%) showed mobility shifts. On DNA sequencing analysis, 11 cases (34.3%) showed point mutations. The results of isotopic SSCP analysis and non-isotopic SSCP analysis were concordant with that of DNA sequencing in 87.5% and 96.9% of cases, respectively. The sensitivity and specificity of detecting p53 mutations by isotopic and non-isotopic SSCP analysis were estimated to be 81.8% and 100%, and 91.0% and 100%, respectively. Non-isotopic SSCP significantly reduced the time and cost to analyze p53 mutation to 7.9% and 16.0% of those of isotopic SSCP, respectively (p<0.005) . Conclusions. Non-isotopic SSCP is a highly sensitive and specific, time-saving, and cost- effective method to detect p53 gene mutations in bladder cancer. This new method may be promising for the clinical application.