Somatic Mutational Analysis of MEN1 and Phenotypic Correlation in Sporadic Parathyroid Tumors

PURPOSE: MEN1 gene mutation causes multiple endocrine neoplasia type 1. It also suggests that somatic MEN1 gene mutation plays a role in sporadic endocrine tumor. In this study, we examined whether somatic mutations of MEN1 gene are responsible for sporadic parathyroid tumors and correlate with clinical manifestations of parathyroid tumors. METHODS: Somatic mutation of MEN1 gene in the formalin-fixed, paraffin-embedded parathyroid tumor tissue from 8 adenomas, 2 carcinomas and 1 hyperplasia were analyzed by direct sequencing. Clinicopathological parameters were reviewed from medical records and compared with the mutational data. RESULTS: Eight of eleven (73%) sporadic parathyroid tumors had somatic MEN1 mutations of 14 different types. In the 14 types, 13 were a point mutation which is composed of 8 missense mutations, 2 nonsense mutations and 3 silent mutations. One of 14 types is a frameshift deletion of 27 base pairs in exon 2. Somatic mutation was frequent in the exon 2 and exon 10. Four types of polymorphism were found. There was no correlation between the presence of mutations and clinicopathological phenotype of parathyroid tumors. CONCLUSION: This result suggests that somatic mutation of MEN1 gene plays a definite role in sporadic parathyroid tumor formation.

The Clinical Significance of Transforming Growth Factor (TGF) beta1, TGF beta Receptor beta II, p53 Protein and K-ras Point Mutation in Pancreatic Cancer

PURPOSE: Many cancers, including pancreatic cancer, harbor defects in TGF beta signaling and are resistant to TGF beta mediated growth inhibition. In addition, the expression of the p53 gene and mutations in K-ras might play an important role in the multistep carcinogenesis of pancreatic cancer. This study examined the expression level of TGF beta 1, TGF beta receptorII (T beta RII), p53 protein and K-ras mutation in pancreatic cancer, along with their role and clinical significance. METHODS: The overexpression of TGF beta 1, T beta RII and p53 protein was evaluated using an immunohistochemical assay. The K-ras mutation was analyzed by PCR-RFLP in the surgical resected pancreatic tissue from 26 pancreatic ductal adenocarcinomas and 5 normal pancreases. RESULTS: Immunohistochemical analysis of TGF beta 1 and T beta RII revealed positive immunostaining in 73.1% and 76.9% of the tumors, respectively, which were significantly higher than the normal pancreas (P=0.008). The p53 protein was positive in none of the 5 normal ducts and 16 out of 26 (61.5%) pancreatic carcinoma specimens. The K-ras mutation was positive in none of the 5 normal ducts, and in 20 of the 26 pancreatic carcinoma specimens (76.9%). The presence of TGF beta1 and T beta RII in the cancer samples was significantly associated with node metastasis, advanced tumor stage (P<0.01), and a short survival time (P<0.05). The p53-positive pancreatic cancers showed a significantly lower survival rate than those with p53-negative tumors (P<0.05). There was no correlation between K-ras mutations and the survival rates. CONCLUSION: The detection of K-ras mutations and TGF beta 1, T beta RII and p53 protein overexpression can predict the prognosis of pancreatic carcinoma patients.

Estimation of Individualized Probabilities of Developing Breast Cancer for Korean Women

PURPOSE: Based on the results of the relative risk model of Korean breast cancer, the aim of this study was to develop a Korean breast cancer risk assessment tool which would display the absolute breast cancer risks of Korean women. METHODS: The tool was developed in the three steps: selection of risk factors and relative risks, calculation of baseline breast cancer incidences, and estimation of absolute breast cancer risks. The risk factors used in this tool were age, family history of first- and second-degree relatives, body mass index, age at first delivery, history of breast-feeding, and a special test on the breasts. A program was developed in an HTML file, which was used for input of the risk factors, and a CGI file, which was used to calculate the risk and display the results. RESULTS: The program was stored in the Internet web page, http://home.dankook.ac.kr/breast/brca/brca.htm. After receiving an input of risk factors, the program was able to calculate the relative risk compared to all the age groups, the estimated absolute risks following 5 and 10 years, and the estimated absolute risks up to ages 64 and 74 years. The estimated risks of Korean women using this tool were less than those reported by the NCI risk assessment tool. The risk of breast cancer was highest in the fifth decade. CONCLUSION: In this study, we developed a web page containing a Korean breast cancer risk assessment tool. This program may be useful for the assessment of individual breast cancer risks, the selection of screening tools, and the evaluation of preventive options for risk reduction.

Estimation of Individualized Probabilities of Developing Breast Cancer for Korean Women

PURPOSE: Based on the results of the relative risk model of Korean breast cancer, the aim of this study was to develop a Korean breast cancer risk assessment tool which would display the absolute breast cancer risks of Korean women. METHODS: The tool was developed in the three steps: selection of risk factors and relative risks, calculation of baseline breast cancer incidences, and estimation of absolute breast cancer risks. The risk factors used in this tool were age, family history of first- and second-degree relatives, body mass index, age at first delivery, history of breast-feeding, and a special test on the breasts. A program was developed in an HTML file, which was used for input of the risk factors, and a CGI file, which was used to calculate the risk and display the results. RESULTS: The program was stored in the Internet web page, http://home.dankook.ac.kr/breast/brca/brca.htm. After receiving an input of risk factors, the program was able to calculate the relative risk compared to all the age groups, the estimated absolute risks following 5 and 10 years, and the estimated absolute risks up to ages 64 and 74 years. The estimated risks of Korean women using this tool were less than those reported by the NCI risk assessment tool. The risk of breast cancer was highest in the fifth decade. CONCLUSION: In this study, we developed a web page containing a Korean breast cancer risk assessment tool. This program may be useful for the assessment of individual breast cancer risks, the selection of screening tools, and the evaluation of preventive options for risk reduction.