p53 mutation in patients with ulcerative colitis in rectal biopsy

(Hyung Joon Kim),(Sae Kyung Chang) 대한내과학회 1998 The Korean Journal of Internal Medicine Vol.13 No.2

N/A Objectives : Long standing ulcerative colitis (UC) has been known to be one of the precancerous diseases of colorectal cancer. Although the frequent loss of p53 allele (LOH) and aneuploidy were reported as the molecular events in carcinoma and dysplasia known as the precursor of UC, p53 genetic alteration was not reported in indefinite dysplasia and UC involved mucosa in long standing UC. Therefore, we investigated the mutational inactivation of the p53 gene in UC patients who showed dysplastic mucosa, as well as non-dysplastic mucosa on H & E stain and, secondly, if there is p53 mutation, we examined the relationship between p53 alteration and clinical data. Method : Sixteen patients with UC who had different duration of colitis were studied by endoscopic examination with rectal mucosal biospies. p53 gene alterations were detected by PCR-SSCP for exon 4-8 and immunohistochemical staining with p53 monoclonal antibody. Results : Among 16 patients, 2 patients (12%) showed dysplasia on H-E stain. The p53 point mutations were detected in 4 (two dysplasia and 2 normal looking mucosa) on PCR-SSCP. 4 patients who had p53 gene mutation were positive in immunohistochemical staining. With regard to clinical characteristics, these patients with p53 point mutation showed poor resoponse to medical treatment. Conclusion : These results suggest that the p53 mutation may be an early molecular event of cancerous change in UC.

Gene Therapy of Brain Tumors : Effects of Adenovirus-mediated Wild Type p53 Gene Transfer in Human Glioma Cells 사람교종세포에서 아데노바이러스 매개체를 이용한 야생형 p53 유전자 전달의 효과

Hong, Yong-Kil,Yung, W.K. Alfred 대한신경외과학회 1996 Journal of Korean neurosurgical society Vol.25 No.8

p53 종양억제유전자의 명확한 작용기전은 아직 밝혀지지 않았지만 WAFI/Cip1과 같은 유전자의 전사(transcription)를 조절하여 종양세포의 성장을 억제하는 것으로 알려졌다. 저자들은 p53 유전자 전달을 통한 유전자 요법의 가능성을 알아보기 위하여 증식력이 없는 아데노바이러스에 야생형 p53 유전자를 집어 넣어 만든 Ad5CMV-p53의 항종양효과를 사람교종세포주(U-251, LG)에서 검사하였다. 단층세포배야을 β-galactosidase 유전자를 지니는 아데노바이러스(Ad5CMV-β-gal) 25 plaque-forming units(PFU)/cell로 48시간 치료한 후 시행한 β-galactosidase 조직화학검사에서, U-251 세포와 LG 세포는 각각 90%, 42%의 유전자 전달효율을 보였다. Ad5CMV-p53 치료에 따른 외인성(exogenous0 p53 단백질의 발현과 WAFI/Cip1 단백질의 유도는 치료 후 24-72 시간에 최고치를 보였다. Ad5CMV-p53 치료는 U-251과 LG 세포의 성장을 각각 85%, 36% 억제하였고 뚜렷한 형태학적 변화를 유도하였다. 종양세포 성자억제에 필요한 Ad5CMV-p53의 적정용량은 10-40 PFU/cell 이었다. 이상의 결과는 Ad5CMV-p53가 사람교종세포에 대해 p53 유전자 전달효율이 높고 항종양 효과가 있음을 의미하며, 이를 이용한 뇌종양의 유전자요법의 가능성을 시사한다. The p53 tumor suppressor gene is one of the genes with greatest therapeutic potential for cancer treatment and its growth inhibitory mechanism is thought to be mediated through the activation of its downstream mediator WAFl/Cip1. In this study, we evaluated the effect of the replication-defective recombinant adenovirus expressing wild-type p53 gene(Ad5CMV-p53) in human glioma cell lines(U-251, LG) harboring mutant-type p53. β galactosidase histochemistry revealed that 90% of the U-251 and 42% the of LG cells are infected with the adenovirus at a multiplicity of infection(M01) of 25 plaque-forming units(PFU)/cell. Immunoblot analyses showed that endogenous p53 protein is expressed at a high level. and significant exogenous p53 protein expression and WAF1/Cip 1 induction peaked on day 1 and day 3 after Ad5CMV-p53 treatment Introduction of Ad5CMV-p53 inhibited the cell growth of U-251(85% inhibition) and LG cells(36% inhibition). and influenced cell morphology The optimal dose of Ad 5CMV p53 for the tumor cells growth inhibition was MOI of 10-40 PFU/cell These results suggest that Ad5CMV-p53 infects human glioma cells and transduces the p53 gene with high efficiency, and could be further developed for the gene therapy of human gliomas.

두경부 종양에서의 암억제 인자인 p53에 대한 연구

서재홍,이미숙,윤신의 대한병리학회 1996 Journal of Pathology and Translational Medicine Vol.30 No.7

원발성 유방암에서 p53 단백발현과 예후와의 상관성에 관한 연구

이학승,이광만,채권묵,문형배 圓光大學校 醫科學硏究所 1995 圓光醫科學 Vol.11 No.1

p53 is a nuclear phosphoprotein which is normally expressed at very low level in all mammalian cells and plays a role in the regulation of cell proliferation. It has also been suggested that normal p53(wild type) serves as a tumor suppressor gene, and inhibits the oncogene-mediated cellular transformation and the rate of cellular proliferation. But, wild type p53 is hardly stained by immunohistochemistry because of its low intracellular concentration and very short half-life. Mutant form of p53 protein is detectable in various human malignancies e.g. colon, stomach, lung and breast cancer by immunohistochemical stain because of its prolonged half-life. In breast cancer, p53 protein expression has been regarded as an unfavorable prognostic factor, but the results of studies about the relationship between the p53 protein expression and prognosis are equivocal. So, author performed this study to evaluate the prognostic significance of p53 expression in 54 patients with primary breast cancer who underwent surgical treatment at Wonkwang University Hospital from October 1985 to September 1991. Follow-up period was 24-91 months (mean: 54.7months). p53 protein was stained by immunohistochemical methods in formalin-fixed, paraffin-embedded tissues using monoclonal antibody(DAKO-p53, DO-7). The prognostic significance of p53 protein was evaluated by positivity and 5-year survival rate, and comparing with well-known prognostic factors of breast cancer. p53 protein was expressed 48.1%(26/54) of primary breast cancers. 5-year survival rate of patients with p53 protein expression was 42.0%, and that of patients without p53 protein expression was 76.4%(p = 0.0277) There was no relationship between p53 protein expression and tumor size, lymph node metastasis, histologic grade or vascular invasion. These results suggest that p53 protein expression is another independent prognostic factor in primary breast cancer.

7, 12-Dimethylbenzanthrancene로 유도된 햄스터의 협낭암모델에서 p53 변이 단백의 발현과 Proliferating Cell Nuclear Antigen에 의한 세포증식능의 변화

이상숙,謝民强,박준식 경북대학교 병원 1998 경북대학교병원의학연구소논문집 Vol.2 No.1

사람의 구강암의 발생기전을 밝히고자 햄스터의 협낭암모델을 이용한 연구가 광범위하게 이루어지고 있다. 두경부의 편평세포암종을 예방하고 조기 발견을 위해서는 이런 종양의 병인을 좀더 깊이 이해하고 위험도를 인지하기 위한 생화학적 또는 유전학적 표지자의 개발이 필요한 실정이다. 본 실험의 결과를 종합해 보면 DMBA도포로 인하여 햄스터 협낭에 정상점막부터 과형성, 이형성 및 편평세포암종의 발생을 시기별로 관찰할 수 있었다. 이는 두경부암의 '영역 암화'와 '다단계 과정'을 지지하는 소견임을 알 수 있었다. 면역조직학적 기법에 의해 p53 변이는 햄스터의 전기암 병소인 과형성부터 나타난 병변이 이형성를 거쳐 편평세포암종으로 진행될수록 빈도가 증가되어 이 종양의 비교적 초기에 p53 변이가 생겨 DMBA로 유도된 햄스터의 편평세포암종의 발생 및 진전에 p53 유전자의 변이가 관여함을 알 수 있었다. 세포의 증식능을 알 수 있는 PCNA 양성인 세포수는 대조군의 정상조직보다 실험군의 전구암 병소에서 더 많았다. 전구암 병소중 이형성이 중정도 이상인 경우 더욱 많이 염색되었다. 그러나 과형성, 과각화증, 이형성와 유두종에서 매우 다양한 PCNA의 발현을 보였다. 편평세포암종에서 전구암 병소보다 더욱 많은 수의 PCNA 양성세포가 관찰되어 병변이 진행될수록 종양의 증식능도 높아짐을 알 수 있었다. 이와 같이 햄스터의 협낭암 발생에 p53 변이가 세포증식능의 증가와 수반되어 암발생의 비교적 초기부터 나타나 p53 변이와 증가된 PCNA 증식능은 두경부암의 재발이나 제2원발암의 발생 위험도를 측정할 수 있는 한 중요한 표지자가 된다고 생각되었다. Squamous cell carcinoma(SCC) of Syrian golden hamster buccal pouch is the best animal model that is histogenetically and morphologically similar to events involved in the development of SCC in human oral cavity. Mutation of the p53 gene is a common event in many human cancers and is also found in certain rodent tumors. Thirty-five SCCs of the buccal pouch of Syrian hamster induced by topical treatment of 7, 12-dimethylbenzanthrancene(DMBA) for 16 weeks were sectioned and examined for potential alterations of p53 expression and PCNA by immunohistochemical methods. Twenty normal control hamsters without DMBA treatment and 25 each hamsters with DMBA treatment for 4 and 8 weeks were also examined. In the mucosa of normal control animals, there was no p53 expression. In hyperplastic mucosal lesions(4 weeks DMBA exposure), the p53 positivity was limited to the basal cell layer and in dysplatic lesions(8 weeks DMBA exposure), the p53 positivity was expanded to the parabasal and superficial layers. In SCCs, p53 staining was diffusely positive in all 35 hamsters. The staining patterns and distribution for p53 protein immunostaining were similar to those of the PCNA staining. These results suggest that p53 and PCNA alterations occur in a multistep fashion during Syrian hamster oral cavity carcinogenesis. Since mutation of the p53 gene and increased PCNA activity appear to be an important step in the pathogenesis of DMBA-induced hamster cheek pouch SCC, one may surmise that similar pathogenetic changes may occur in hauman oral cavity SCC. Therefore, p53 alteration and PCNA positivity can be utilized for risk assessment and may serve as biomarkers for oral carcinogenesis in both Syrian hamsters and humans.(Korean J Otolaryngol 38 : 9,1995)

유방암 조직의 p53 단백 및 Cathepsin D 발현 : ER/PR 및 다른 예후인자와의 연관성에 관하여 Correlation with ER/PR and Other Prognostic Factors

강미선,윤혜경 인제대학교 1966 仁濟醫學 Vol.17 No.4

유방암의 예후인자로 가장 중요한 것이 림프절 전이 여부이다. 그러나 림프절 전이를 알 수 없거나 림프절 전이가 없는 환자의 예후 판정 인자에 대해서도 많은 연구가 이루어지고 있다. 그중 에스트로젠 및 프로제스테론 수용체(ER/PR) 유무, p53 유전자 및 일종의 단백분해효소로 알려진 cathepsin D의 존재 유무 등이 예후인자로서 거론되고 있다. 본 연구는 p53 및 cathepsin D의 예후 인자로서의 의의를 확인해 보고자 면역조직화학적 방법으로 상기 두 물질의 발현율을 조사하여 기존 알려진 유방암의 예후인자들인 환자의 연령, 종양의 크기, 분화도, 림프절 전이 유무, ER/PR 상태와의 연관성을 살펴보았다. p53 gene mutation is involved in carcinogenesis of many human cancers. In breaset cancer, it is known that p53 positivity is related to poor prognosis. The materials for this study were obtained from 44 cases of breast cancer regardless of histologic types, For the evaluation of the significance as prognostic indicators, the immunohistochemical expression rates of p53 protein and cathepsin D were compared with other proven prognostic factors of breast cancer such as patient's age, tumor size, histologic grade, axillary lymph node metastasis, and ER/PR status. The results were as follows ; 1.The expression rates of p53 protein and cathepsin D were 40.90% and 36.36%, respectively. 2.Positive reaction of p53 protein was related to high histologic grade and older(more than 50 years old) age groups.(p<0.05) But no significant differences were recognized between p53 expression and tumor size, lymph node status and ER/PR state. 3.Positive cathepsin D expression was related to "good prognosis" groups such as less than 50 years old, less than 2cm in diameter, negative lymph node metastasis, ER/PR and negative p53 expression, but their differences were not statistically significant. 4.Cathepsin D expression rate was also high in high histologic grade like p53 expression, but the differences were not significant. In conclusion, positive expression of p53 protein is regarded as another poor prognostic factor because of good correlation with high histologic grade. Unfortunately present study can't afford the significance of cathepsin D expression as a prognostic indicator. Further studies on cathepsin D expression of both tumor cells and stromal cells should be performed for the evaluation on the usefulness as a prognostic indicator.

급성골수성백혈병 환자에서의 p53 유전자 돌연변이

정철원,이상재,김원석,안명주,정태준,김인순,최일영,김시영,윤휘중 大韓血液學會 1998 大韓血液學會誌 Vol.33 No.3

대장직장암에서 p53 및 Ki-67 발현의 임상적 의의

허정욱,김형록,김영진,조상혁 대한대장항문학회 2009 Annals of Coloproctolgy Vol.25 No.2

Purpose: This study aimed to evaluate the clinical significance of p53 and Ki-67 expressions in patients with colorectal cancer. Methods: Immunohistochemical expressions of p53 and Ki-67 in 205 patients with colorectal cancer were examined. Results were correlated with clinical and pathological parameters. Results: Overexpression of p53 was significantly associated with a proximal location of the tumor (P=0.031) and with lymph node involvement (P=0.030); however, Ki-67 expression was not correlated with any of the clinicopathological variables. Positive p53 staining was significantly associated with a higher level of Ki-67 (P=0.009). Conclusion: Overexpression of p53 was strongly correlated with lymph node metastasis in colorectal cancer; thus, p53 may be used as a possible prognostic marker in patients with colorectal cancer. Purpose: This study aimed to evaluate the clinical significance of p53 and Ki-67 expressions in patients with colorectal cancer. Methods: Immunohistochemical expressions of p53 and Ki-67 in 205 patients with colorectal cancer were examined. Results were correlated with clinical and pathological parameters. Results: Overexpression of p53 was significantly associated with a proximal location of the tumor (P=0.031) and with lymph node involvement (P=0.030); however, Ki-67 expression was not correlated with any of the clinicopathological variables. Positive p53 staining was significantly associated with a higher level of Ki-67 (P=0.009). Conclusion: Overexpression of p53 was strongly correlated with lymph node metastasis in colorectal cancer; thus, p53 may be used as a possible prognostic marker in patients with colorectal cancer.

기관지도말 표본에서 p53단백 발현의 진단적 의의

이상숙,배지연,강유나,조영록,김시남,박남조,김선영,김정희,Lee, Sang-Sook,Bae, Ji-Yeon,Kang, Yu-Na,Cho, Young-Rok,Kim, Si-Nam,Park, Nam-Jo,Kim, Seun-Young,Kim, Jung-Hi 대한세포병리학회 1996 대한세포병리학회지 Vol.7 No.2

Abnormalities of p53 gene are common in lung cancers and are associated with immunologically detectable p53 protein. p53 immunoreactivity is uncommon in normal cells but is frequently seen in neoplasia. Therefore, assessment of p53 expression may assist in the cytological diagnosis of malignancy. The usefulness of p53 immunostaining as a marker of malignancy in the cytological analysis of bronchial brush specimens from the patients with lung cancers was investigated in this study. A total of 71 bronchial brush samples submitted for cytologic diagnosis were immunostained with D07, a monoclonal antibody to recombinant p53 protein. Resultant p53 data were correlated with cytologic diagnosis and clinical information. Of the 17 smears with a benign cytodiagnosis, all were p53 negative. Of the 40 cases with a malignant cytodiagnosis (histologically confirmed), 35 were p53 positive and 5 were negative. Of the 14 cases that were cytologically suspicious but nondiagnostic for malignancy, 11 were p53 positive, 9 of which were subsequently proved to be malignant by histologic examination, and the remaining 2 cases were tuberculosis clinically. Forty four of 51 histologically confirmed lung carcinomas were p53 positive, including 25 of 28 squamous cell carcinomas, 13 of 17 small cell carcinomas, 3 of 3 adenocarcinomas, and 3 of 3 large cell undifferentiated carcinomas. These results suggest that p53 immunostaining could be of value as a marker of malignancy in the cytologic examination of bronchial brush specimens. Furthermore, we have shown the possible clinical utility of p53 immunostaining in cytopathological diagnosis, that is, as a valuable adjunct to morphological assessment in the analysis of cytopathologically suspicious cases.

후두 및 하인두 암종에서 p53단백 발현과 Espstein-Barr Virus 검출

최영환,도남용,나한조,이도용,노용훈,김완수,최종선 조선대학교 2001 The Medical Journal of Chosun University Vol.26 No.2

Background and Objectives : When p53 cancer suppressor gene, occurs gene deletion or point mutation, malignancy develops by loss of p53 function with abnormal p53 protein. The Epstein-Barr virus (EBV) is the causative agent of certain type of lymphoma and undifferentiated nasopharyngeal carcinoma. However, the role of EBV as a causative factor in other head &eck tumors is not fully elucidated except nasopharyngeal carcinoma. This study, the author examined that p53 expression and detection rate of EBV correlate to development of laryngeal and hypopharyngeal squamous cell carcinoma(SCC) and play the possible role of prognostic indicators. Materials and Methods : Formalin-fixed, paraffin-embedded tissue specimen from 32 cases of larynx and hypopharyngeal squamous cell carcinomas were studied by immunohistochemical staining for p53 and EBV. The results of analysis were compared with clinicopathological parameters. Results : p53 expression was 56.3% (18 cases) and the detection rate of EBV was 43.6% (14 cases) of 32 cases in laryngeal and hypopharyngeal squamous cell carcinomas. p53 expression was correlate with histologic grade (p<05) only. Detection of EBV was not correlate with clinicopathological parmeters. Conclusion : These results suggest p53 expression and the detection of EBV may be related with development of laryngeal and hypopharyngeal squamous cell carcinoma. And, the expression of p53 protein can be used as a prognosticator in laryngeal and hypopharyngeal squamous cell carcinoma under certain limitation.