| Title | Clinical Implications of Microsatellite Instability and MLH1 Gene Inactivation in Sporadic Insulinomas |
| Authors | Mei, Mei Deng, Dajun Liu, Tong-Hua Sang, Xin-Ting Lu, Xin Xiang, Hong-Ding Zhou, Jing Wu, HaiYan Yang, YingMai Chen, Jie Lu, Chong-Mei Chen, Yuan-Jia |
| Affiliation | Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Gastroenterol, Beijing 100730, Peoples R China. Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Pathol, Beijing 100730, Peoples R China. Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Surg, Beijing 100730, Peoples R China. Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Endocrinol,Minist Hlth,Key Lab Endocrinol, Beijing 100730, Peoples R China. Peking Univ, Sch Oncol, Dept Etiol, Minist Educ,Key Lab Carcinogenesis & Translat Res, Beijing 100730, Peoples R China. Beijing Canc Hosp Inst, Beijing 100730, Peoples R China. |
| Keywords | PANCREATIC ENDOCRINE NEOPLASMS NONPOLYPOSIS COLORECTAL-CANCER GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS PERFORMANCE LIQUID-CHROMATOGRAPHY MISMATCH REPAIR GENE PROMOTER METHYLATION MUTATION ANALYSIS CHROMOSOME 1Q COLON-CANCER HMLH1 |
| Issue Date | 2009 |
| Publisher | journal of clinical endocrinology metabolism |
| Citation | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM.2009,94,(9),3448-3457. |
| Abstract | Context: The molecular pathogenesis of sporadic insulinomas is unknown. There is a lack of biomarker to distinguish benign and malignant form of insulinoma. Objective: Our objective was to confirm the occurrence of microsatellite instability (MSI) in insulinomas, to identify alterations of mismatch repair (MMR) genes in the tumors, and to evaluate the possibility to distinguish benign and malignant insulinoma or to predict the clinical outcome of patients with these alterations. Design and Patients: We detected MSI and inactivation of MLH1 gene in 55 sporadic insulinomas by PCR, immunohistochemical staining, allelic typing, analysis of promoter methylation, and exon mutations. Their correlations with clinicopathological characteristics were analyzed with univariate and multivariate statistic analysis. Results: A high rate of MSI (MSI-H) was found in 33% of sporadic insulinomas. Reduced expression of mutL homolog 1 (MLH1) protein was observed in 36% of insulinomas and correlated with MSI-H (P = 0.008). Promoter methylation and loss of heterozygosity of MLH1 gene was found in 31 and 49% of insulinomas, respectively. Reduced expression of MLH1 and MSI-H were significantly associated with both tumor malignancy (P = 0.033 and P = 4.8 x 10(-6), respectively) and incurable disease (P = 0.006 and P = 0.001, respectively). Conclusion: High frequency of MSI occurred in sporadic insulinomas. The silencing of MLH1 gene may partially contribute to the MSI-H in the tumors. Assessing MSI-Handexpressions of MLH1 could be used to distinguish benign and malignant insulinomas and to predict the outcome of patients. (J Clin Endocrinol Metab 94: 3448-3457, 2009) |
| URI | http://hdl.handle.net/20.500.11897/397036 |
| ISSN | 0021-972X |
| DOI | 10.1210/jc.2009-0173 |
| Indexed | SCI(E) |
| Appears in Collections: | 北京肿瘤医院 |
