Serum Anti-p53 Antibodies and p53 Protein Expression and Their Prognostic Relevance in Patients with Gastric Cance / 대한진단검사의학회지

BACKGROUND: Several cancer patients have developed antibodies that recognize the overexpressed p53 protein. In some tumor types, the presence of these antibodies is associated with a poor prognosis. Gastric cancer is a highly prevalent disease associated with a high mortality rate, so there is a need for improved serological markers for disease detection and disease behavior. METHODS: To evaluate the clinical relevance of anti-p53 antibodies and tissue p53 protein expression in gastric cancer, we investigated the presence of serum anti-p53 antibodies in 61 gastric cancer patients, using two enzyme-linked immuno-sorbent assay systems (Dianova p53-autoantibodies ELISA Kit, Hamburg, Germany (A); Pharma Cell Anti-p53 ELISA Kit II, Paris, France (B)), and p53 protein expression was immunohistochemically stained. RESULTS: We have detected serum anti-p53 antibodies in 9.8% (6/61), 18.0% (11/61) of gastric cancer patients before operation by using the A and B kit, respectively, but in none of 21 cancer-free individuals. The detectable expression of p53 protein in tissue was recognized in 49.2% (30/61) of gastric cancer patients, and in 100% (6/6) and 72.7% (7/11) of the patients with anti-p53 Ab by using the A and B kit. The presence of anti-p53 antibodies was significantly associated with high tumor stages, lymph node metastasis, advanced cancers, intestinal histological type, larger tumor size and infiltrating type, and short survival. The overexpression of the p53 protein was significantly associated with large sized tumors, advanced cancers, high tumor stage (III, IV), lymph node metastasis, distant metastasis, early death and high recurrence rate, and short survival. A positive rate for gastic CONCLUSIONS: We have shown that anti-p53 antibodies are closely related to p53 protein overexpression in tumor tissues and could be useful not only as a predictor of an unfavorable prognosis before operation, but also as a serological tumor marker for an increase in the detection rate of gastric cancer by a combination assay with anti-p53 antibodies, CEA and CA 19-9, although not as a screening test.

The Prognostic Significance of Immunohistochemically Detected Isolated Tumor Cells in Lymph Node in Colorectal Cancer

PURPOSE: Metastasis of a colorectal carcinoma to regional lymph nodes indicates poor prognosis. The detection of lymph node metastasis is routinely performed by his topathological analysis of hematoxylin-eosin (H&E) stained sections. However the routine histological technique may fail to detect isolated tumor cells in lymph nodes. The aims of this study are to elucidate the prognostic significance of the presence of isolated tumor cells in the regional lymph nodes in colorectal cancer, and to elucidate the correlation between the presence of isolated tumor cells and p53 protein expression in the primary colorectal cancer tissue. METHODS: We used immunohistochemical staining with anti-cytokeratin antibody to examine 452 lymph nodes in 24 patients (11 recurrent and 13 nonrecurrent) who were histologically determined Astler-Coller B. And we used immunohistochemical staining with p53 protein to examine primary colorectal cancer tissues of the patients. RESULTS: Immunohistochemical staining of cytokeratin revealed the presence of isolated tumor cells in 5/13 patients (38.5%), 5/214 lymph nodes (2.34%) in the nonrecurrent group and 6/11 patients (54.6%), 11/244 lymph nodes (4.51%) in the recurrent group, respectively. The detection rate of isolated tumor cells in the recurrent group was slightly higher than nonrecurrent group, but the difference was not significant statistically. The expression rate of p53 protein was 23.1% (3/13) in the nonrecurrent group and 36.4% (4/11) in the recurrent group, respectively. The expression rate of the p53 protein was not significantly correlated with the presence of isolated tumor cells in regional lymph nodes and the rate of tumor recurrence. CONCLUSIONS: The presence of isolated tumor cells in regional lymph nodes was not a prognostic indicator in predicting recurrence in histologically determined Astler- Collar B colorectal cancer patients.

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.

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.

Studies on anti proliferation and inducing apoptosis effects of CIK cells against MGC 803 gastric cancer cell lines / 中国免疫学杂志

Objective:To study the anti proliferation and inducing apoptosis effects of cytokine induced killer cells CIK cells on MGC 803 gastric cancer cell lines and to probe its underlying mechanism.Methods:To detect the anti proliferation and the cytotoxicity of CIK cells on MGC 803 gastric cancer line by MTT assay.The morphological changes of the apoptosis cell were observed by HE stain, scanning and transmission electron microscope. The positive expression of p53, p16,C myc were determined by immunocytochemistry (ICC).Results:MTT assay showed that the inhibitive rate inhanced obviously with the addition of Effect/Target rate and extension of time ( P

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 Protein Expression in Infiltrating Ductal Carcinoma of the Breast

Overexpression of the nuclear phosphoprotein p53 is the most common genetic anomaly found in primary human cancer and mutation of the tumor suppressor gene p53 has been identified in breast cancer cell lines. In this study, we evaluated the prognostic significance of p53 protein expression in patients with mammary infiltrating ductal carcinoma and its correlation with histopathologic grade, lymph node status, tumor size, p53 protein expression and survival. Among 53 cases, p53 protein expression was detected in 26(49.1%) cases by immunohistochemistry. There was no correlation between p53 protein overexpression and histopathologic grade(p=0.09) or lymph node status(p=0.38) and between survival and histopathologic grade (p=0.68) or lymph node status(p=0.52). However, p53 protein expression was significantly correlated with survival(p=0.01) and patients with p53 protein-positive tumors showed poorer survival times. But Cox multivariate analysis showed the lymph node status is significant(p=0.01). The authors conclude that the presence of mutant p53 protein and lymph node status may serve a prognostic role, in a subset of mammary infiltrating ductal carcinoma cases.