Two Cases of Acute Leukemic Transformation with a Chromosome 17 Abnormality and p53 Overexpression Evolving from Essential Thrombocythemia

Essential thrombocythemia (ET) is a clonalmyeloproliferative disorder that can rarely transform into acute leukemia in 1~5% of cases. A recent study has found that a significant proportion of leukemic cases from ET were associated with a cytogenetic abnormality (17p deletion). Herein, we report two cases of acute myeloid leukemic transformations harboring a 17p abnormality from a series of 119 ET patients. The first case, a 48-year-old female, developed acute myeloid leukemia with maturation (AML-M2) accompanying myelodysplasia was diagnosed 6.1 years after the initial diagnosis of ET. She was treated with hydroxyurea. Her karyotype showed a monosomy 17. The second case, a 61-year-old male, developed acute megakaryoblastic leukemia (AML-M7) with a very complex hyperdiploidy including addition of 17p13 that developed 6.5 years after the initial diagnosis. He was treated with hydroxyurea and anagrelide. The immunohistochemistry showed p53 overexpression in both cases. Our cases support the specificity of chromosome 17 abnormality and p53 overexpression in acute leukemic transformation from ET.

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 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.

The Prognostic Significance of the p53 Overexpession on Complete Response and Survival in Preoperative Chemoradiotherapy Treated Squamous Cell Esophageal Carcinoma / 대한암학회지

PURPOSE: To determine the frequency of p53 overexpression and to analyse the relationship between p53 overexpression and complete response rate, survival in locoregionl squamous cell esophageal cancers treated with preoperative chemoradiation multimodality approaches. MATERIALS AND METHODS: Using a microwave oven heating method, we have detected p53 overexpression by immunohistochemically with a monoclonal antibody(DO-7) in formalin- fixed paraffin-embedded samples of 42 patients with locoregional squamous cell esophageal cancer, who treated with concurrent chemotherapy and radiatian followed by surgery. RESULTS: In 27 of 42 tumors(64.2%), nuclear immunoreactivity for the p53 protein was detected. Complete response rate, evaluated in surgical specimen 3-4 weeks after chemoradiation seemed to be high in p53 positive group compared to p53 negative group, however, there was no statistically significant difference in acquiring better complete response rate, overall survival and progression free survival between p53 positive and p53 negative group(p=0.0546, p=0.0599, p= 0.6832). Complete response group(n=17) survived longer than non-complete response group(n=25)(p=0.0010). CONCLUSION: The results indicate that p53 is not a statistically significant prognostic factor in obtaining better complete response rate, overall survival and progression free survival of the patients with esophageal carcinoma treated with preoperative chemoradiotherapy. Additional studies are warranted for further evaluation.

Overexpression of p53 as a Prognostic Marker in Breast Cancer

BACKGROUND: The treatment plan for breast cancer depends on the axillary lymph-node status. Because of improved screening methods, the number and the proportion of node-negative patients are increasing, leading to a need to search for a reliable prognostic marker. Assessment of prognostic markers, is of major concern for the application of adjuvant treatment regimens, independenent of the axillary lymph-node status. METHODS: The study samples consisting of 96 primary breast cancer tissues were analyzed immunohistochemically for the presence of p53 protein in a paraffin-embedded material. The reaction to monoclonal mouse anti-human p53 protein (DAKO-p53, DO-7) (DAKO, Denmark) produced our experimental data. RESULTS: Nuclear accumulation of the p53 protein suspected to be an independent marker of dedifferentiation, regardless of the lymph-node status. In our study the p53 positivity was 56.25% (54/96), and statistically p53 positivity was not affected by menopausal status, lymph-node metastasis, tumor size, age, presence of the estrogen receptor and the progesterone receptor, and pathologic grading. CONCLUSION: We weren't able to prove statistically that overexpression of p53 is an independent prognostic factor in breast cancer. With more cases of breast cancer involving the monoclonal antibody, a study of the correlation of overall survival and disease-free survival with lymph-node metastasis, pathologic grade, and p53 overexpression is necessary to decide on an early breast-cander treatment modality by using a prognostic marker such as p53.

P53 overexpression in gastric adenocarcinoma with Helicobacter pylori infection

Gastric carcinogenesis has been studied in various aspects. Helicobacter pylori (Hp) infection and mutation of the p53 tumor suppressor gene have recently been argued to be important factors of gastric carcinogenesis. There have been many studies to determine the precise mechanism of how Hp is related to gastric cancer, but it is so far still unknown. We studied the relationship of Hp infection and p53 overexpression and tried to discover some significance in clinicopathologic factors such as age, sex, stage, site, differentiation and gross morphology. Ninety-six patients who were diagnosed with gastric cancer at Severance Hospital, Yonsei University Medical College from November 1995 to March 1996, and 96 control patients of non-ulcer dyspepsia (NUD) were studied by endoscopic biopsy of normal gastric tissue and cancer tissue. They also underwent the CLO (Delta West, Melbourne, Western Australia) test for Hp positivity and p53 immunohistochemical stain for p53 positivity. These data were analyzed for comparison with the clinicopathologic characteristics of gastric cancers. In conclusion, the differentiated group cancer had a significantly high Hp positivity and p53 positivity. There is a possibility that Hp infection and p53 tumor suppressor gene mutation might be significantly related in the gastric carcinogenic process of well- and moderately-differentiated adenocarcinomas, but further study is necessary to determine more direct clues on the carcinogenic roles of these factors.

The Overxpression of p53 in gestational Trophoblastic Disease and Normal Human Placenta / 대한부인종양콜포스코피학회잡지

Mutations in the tumor suppressor p53 gene are the most frequently observed genetic lesions in human cancers. It seems that wild type p53 does significant role on growth and differentiation of normal cells, Mutations and allelic loss of the p53 gene are thought to be a cause of tumor development and to be correlated with the prognostic factors in various human cancers such as breast, ovary and lung cancer. Mutant p53 proteins have a prolonged half-life and can be detected by immunohistochemistry. In case of GTD(gestational trophoblastic disease), although the mutation of p53 gene mutation was revealed to be very rare, the overexpression of p53 in immunohistochemical staining has been reported in wide range of discrepancy and its role or prognostic significance in GTD is uncertain. This study is performed to define the status of p53 overexpression in GTD and to evaluate the correlations between p53 overexpression and prognostic factors of GTD. THE RESULTS WERE AS FOLLOWS: 1. p53 overexpression was detected in none of normal placental tissue, in 58.3%(14/24) of hydatidiform mole, in 15%(6/8) of invasive mole, in 75%(3/4) of choriocarcinoma, and in 100%(1/1) of placental site trophoblastic tumor, and showed significant difference between normal placenta and GTD. We could not find any difference of the p53 overexpression between benign group(H-mole) of GTD and malignant one(invasive mole, choriocarcinoma, and placental site trophoblastic tumor) 2. In H-mole, low-risk group showed significantly higher prevalence of p53 overexpression than high-risk group did. In malignant group, there is no difference in the prevalence of p53 overexpression between early(FIGO stage I) and late(II- IV)stage-diseases, but the prevalence of p53 overexpression of low-risk group is slightly higher than that of high-risk group although we failed to find statistical significance. In conclusion, the high prevalence of p53 overexpression in GTD suggests that p53 may have a certain role in the pathogenesis of GTD or at least represent generalized DNA damage or genetic instability of GTD. And the higher prevalence of p53 overexpression in low-risk group suggests that accumulation of wild-type p53 may be related with favorable prognosis in GTD.