Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability
| العنوان: | Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability |
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| المؤلفون: | Iva Maestri, Roberta Gafà, Alessandra Santini, Stefano Ferretti, Giovanni Lanza, Maurizio Matteuzzi, Luigi Cavazzini |
| المصدر: | Cancer. 89:2025-2037 |
| بيانات النشر: | Wiley, 2000. |
| سنة النشر: | 2000 |
| مصطلحات موضوعية: | congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, Pathology, medicine.medical_specialty, Colorectal cancer, nutritional and metabolic diseases, Rectum, Cancer, Microsatellite instability, Biology, medicine.disease, digestive system diseases, High-Frequency Microsatellite Instability, medicine.anatomical_structure, Oncology, medicine, Adenocarcinoma, Immunohistochemistry, Microsatellite, neoplasms |
| الوصف: | BACKGROUND Widespread microsatellite instability (MSI) occurs in nearly 15% of sporadic colorectal cancers. Large bowel carcinomas with high-frequency MSI (MSI-H) (instability at ≥ 30% of microsatellite loci) are believed to display distinctive pathologic features and to behave less aggressively than microsatellite-stable (MSS) tumors and carcinomas with low-frequency MSI (MSI-L) (instability at < 30% of microsatellite loci). The aim of the current study was to accurately define the clinicopathologic and biologic features of MSI-H sporadic colorectal carcinomas. METHODS MSI status was evaluated in 216 large bowel adenocarcinomas using polymerase chain reaction (PCR) and 6 microsatellite markers. Tumors that showed instability with at least two microsatellite markers were classified as MSI-H, whereas the other tumors were classified as MSI-L (instability at one locus) or MSS (no instability). Expression of p53, hMLH1, and hMSH2 gene products was determined by immunohistochemistry, and DNA ploidy pattern was determined by flow cytometry. The prognostic significance of MSI status was assessed by univariate and multivariate survival analyses. RESULTS The significantly different pathologic features of MSI-H carcinomas were proximal location; large size; mucinous and medullary histotype; poor differentiation; expanding pattern of growth; more frequent Crohn-like conspicuous lymphoid reaction; and low incidence of extramural vein invasion. Most MSI-H tumors were DNA diploid (33 of 40 tumors; 82.5%) and p53 negative (34 of 44 tumors; 77.3%). Conversely, DNA aneuploidy and p53 overexpression were observed in 82.3% (130 of 158 tumors; P < 0.0001) and 54.1% (93 of 172 tumors; P = 0.0002) of MSI-L/MSS tumors, respectively. Loss of hMLH1 or hMSH2 expression was detected in a high fraction of MSI-H carcinomas (86.0%). Patients with MSI-H tumors showed a better clinical outcome than patients with MSI-L/MSS tumors (P = 0.0017). Furthermore, in multivariate analysis that included conventional clinicopathologic parameters, MSI status, and p53 expression as covariates, MSI status was a significant independent prognostic indicator of disease specific survival. CONCLUSIONS Assessment of MSI status is an essential step in the genetic characterization of large bowel carcinomas and identifies a subset of tumors with distinct clinical, pathologic, and biologic features. Cancer 2000;89:2025–37. © 2000 American Cancer Society. |
| تدمد: | 1097-0142 0008-543X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::512fc6d0414d23f33c0e940d9b626713Test https://doi.org/10.1002/1097-0142Test(20001115)89:10<2025::aid-cncr1>3.0.co;2-s |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........512fc6d0414d23f33c0e940d9b626713 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970142 0008543X |
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