Journal of Pathology and Translational Medicine

Original Articles

Loss of Heterozygosity Affecting the APC and p53 Tumor Suppressor Gene Loci in Colorectal Cancers and Its Prognostic Significance.: Eun Deok Chang, Won Sang Park, Byung Kee Kim, Sun Moo Kim, Sang In Shim; Korean J Pathol. 1997;31(3):191-200.

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Abstract PDF: Development of the human colorectal cancer is associated with several distinct genetic abnormalities involving both dominant-acting oncogenes (K-ras, c-src) and tumor suppressor genes (APC, DCC, p53) which undergo inactivation or loss. In colorectal tumors, the common molecular alteration is localized in the 17p13 and 5q21 loci encoding the p53 and the APC gene, respectively. The identification of these genes may help the understanding of the pathogenesis of colorectal neoplasia. In order to determine whether the frequency of the genetic alterations varies with sex, age, tumor size, or site, including pathologic parameters, such as degree of differentiation, tumor stage, mucin component, lymphoid reaction, tumor invasion pattern, vein and nerve invasion, lymph node metastasis, and other parameters, such as disease-free survival, distant metastasis and patient outcome, the authors analyzed the loss of heterozygosity (LOH) of the APC and the p53 genes in paraffin-embedded specimens of 48 colorectal cancers by use of the polymerase chain reaction and restriction fragment length polymorphism. The results were as follows: the LOH affecting the APC was found in 15 out of 31 (48.4%) heterozygous patients, while the LOH of the p53 locus was observed in 11 out of 26 (42.3%) patients. Among 48 patients, the LOH at both the APC and the p53 loci was observed in five (10.4%) patient. No statistically significant associations were found between the LOH of the APC gene and the proposed parameters. The relationship between the LOH of the p53 and the histologic differentiation, lymphoid reaction was significant (P<0.05), but survival was not correlated. Statistically significant associations were found between overall survival of the colorectal cancer patients and distant metastasis, Astler-Coller stage, lymphoid reaction, invasion pattern, nerve invasion, vein invasion, lymph node metastasis, and disease free survival. The above results suggest that the LOH of the p53 genes could be involved in the progression of colorectal cancers. However, neither the LOH of the APC nor that of the p53 have significant association with survival of the colorectal cancer patients.

Alteration of p53 Tumor Suppressor Gene in Hyperplastic Lesions and Adenocarcinomas of Uterine Endometrium - Immunohistochemistry and PCR-SSCP.: Eun Kyung Kim, Chan Kum Park, Gu Kong, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1997;31(7):662-671.

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Abstract PDF: To investigate the role of the p53 gene in the development of endometrial adenocarcinoma and to study the relation between alteration of the p53 gene and histologic grade, the author studied the alteration of thep53 gene in hyperplastic lesions and adenocarcinomas of the uterine endometrium. The study was carried out with immunohistochemical stain and PCR-SSCP. The materials included ten cases of endometrial hyperplasia (five simple and five atypical complex) and 18 cases of endometrial adenocarcinoma. Overexpression of the p53 protein were found in one of five atypical complex hyperplasias (20%) and 11 of 18 adenocarcinomas (61.1%). The intensity of p53 overexpression appeared to have increasing tendency with higher histologic grade of adenocarcinomas. Among the II cases of adenocarcinoma that overexpressed p53 protien, five cases (45.5%) were found to have mutations by PCR-SSCP. One was grade 1 (20%), two were grade 11 (25%), and two were grade III (40%). The sites of mutation were three exon 8, one exon 5, and one exon 6. In conclusion, alteration of the p53 gene may paly a role in the development of endometrial adenocarcinoma and appears to occur as a late event in carcinogenesis.HHowever, inactivation of the p53 gene in early stage of tumor development cannot be excluded.

DNA Sequencing of p53 Gene Mutation in Colorectal Carcinomas.: Young Ran Shim, Joon Hyuk Choi, Won Hee Choi; Korean J Pathol. 1999;33(6):422-433.

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Abstract PDF: Mutations in the p53 gene occur during the development of colorectal carcinomas, and play an important role in the conversion of adenoma into carcinoma. To detect the p53 gene mutation and its pattern of expression in colorectal carcinomas, polymerase chain reaction for exons 5, 6, 7, and 8, recombinant gene cloning, and automated DNA sequencing were performed with 30 fresh colorectal carcinomas. Each tissue was also analyzed by immunohistochemical staining for p53 protein. p53 protein was detected in 25 of 30 (83.3%) colorectal carcinomas by immunohistochemical study. p53 mutation was detected in 4 of 30 (13.3%) colorectal carcinomas. The distribution of these mutations among these exons investigated was as follows: Three mutations in exon 5 (66.7%) and 1 mutation in exon 7 (33.3%). One case with mutation in exon 5 had mutations at three different codons. Mutations in exon 5 were found at codon 153 (GGG to AGG: Gly to Arg), 170 (TGC to GGC: Cys to Gly), 186 (CTA to TTA: silent mutation), 158 (GCG to ACG: Ala to Thr), and 176 (ACG to ATG: Thr to Met). Mutation in exon 7 was found at codon 248 (AGG to AGA: silent mutation). Four of them were missense mutations. Two of 6 mutations were silent mutations. Five transition mutations and 1 transversion mutation were also detected. All cases with mutations by automated DNA sequencing showed positive p53 protein immunohistochemical stainining. In conclusion, p53 gene mutation was detected in 4 of 30 (13.3%) colorectal carcinomas, located in codon 153, 158, 170, 176, and 186 of exon 5 and codon 248 of exon 7. Further studies are needed to evaluate the significance of the codon 153 mutation which was not recognized in other studies on colorectal carcinomas.

Human Papillomavirus Type 16, 18, and 33 Infection in Adenocarcinoma of the Uterine Cervix: Analysis of the p53 Gene Mutation and the Clincopathologic Correlation.: Kwang Sun Suh, Seong Jun Cho, Sun Young Na, Heung Tae Noh, Sang Ryun Nam; Korean J Pathol. 2004;38(5):295-300.

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Abstract PDF: BACKGROUND
Current evidence implicates specific types of the human papillomavirus (HPV) are involved in the development of cervical cancer. In HPV-negative cervical carcinomas, p53 mutation is thought to be a mechanism of oncogenesis. The purpose of this study was to evaluate the prevalence of p53 mutations in cervical adenocarcinomas and to investigate their correlation with HPV status and clinicopathologic parameters.
METHODS
A series of 38 primary cervical adenocarcinomas was analyzed for both HPV infection and p53 mutations. The HPV 16, 18, and 33 status was investigated by PCR amplification. The point mutations of the p53 gene were detected by the PCR-SSCP technique.
RESULTS
The prevalence of HPV 16, 18, or 33 infection was 73.7% (28/38). HPV 16 was present in 12 cases, HPV 18 was present in 15 cases, and HPV 33 was positive in one case. There was only one case that was positive for 18 as well as a p53 mutation in exon 6.
CONCLUSIONS
Our results indicate that HPV 18 infection was more common in cervical adenocarcinomas than HPV 16 infection. Mutant p53 was rarely found in cervical adenocarcinomas regardless of the type of HPV infection. There was no correlation between HPV infection and clinical stage or pathologic type of tumor.

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