Molecular Carcinogenesis of Endometrial Cancer
In 1983, Bokhman proposed a dualistic model of endometrial tumorigenesis based on the clinical observations and clinicopathologic correlations. The majority of endometrial cancers (approximately 70–80%), designated as type I carcinomas, follow the estrogen-related pathway. Histologically, most of th...
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| Format: | Article |
| Language: | English |
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Elsevier
2007-03-01
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| Series: | Taiwanese Journal of Obstetrics & Gynecology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1028455908601023 |
| _version_ | 1818520619971510272 |
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| author | Fu-Shing Liu |
| author_facet | Fu-Shing Liu |
| author_sort | Fu-Shing Liu |
| collection | DOAJ |
| description | In 1983, Bokhman proposed a dualistic model of endometrial tumorigenesis based on the clinical observations and clinicopathologic correlations. The majority of endometrial cancers (approximately 70–80%), designated as type I carcinomas, follow the estrogen-related pathway. Histologically, most of the type I tumors seem to arise in the background of hyperplastic endometrium, show an endometrioid differentiation, and are of low grade. Clinically, they are overall characterized by a favorable behavior. Another 10–20% of endometrial cancers, designated as type II carcinomas, follow the estrogen-unrelated pathway and arise in the background of atrophic endometrium. Type II tumors usually occur at an older age, approximately 5–10 years later than type I tumors. They are typically high-grade carcinomas of nonendometrioid differentiation, most frequently serous, less frequently clear cell. Type II carcinomas behave as an aggressive clinical course and poor prognosis. This dualistic model was subsequently supported by the molecular studies, approximately a decade later. At present, endometrioid and serous carcinoma, which represent the major phenotypes of types I and II endometrial carcinomas, respectively, are characterized by distinctive types of genetic instability and molecular alterations. In endometrioid (type I) carcinoma, four major genetic changes are responsible for the tumorigenesis, i.e. silencing of PTEN tumor suppressor gene, presence of microsatellite instability due to alterations of the mismatch repair genes, mutation of K-ras protooncogene, and alteration of β-catenin gene. On the other hand, p53 mutation and overexpression of Her2/neu oncogene are two major genetic alterations in serous and clear cell (type II) carcinomas. However, like in any model, there is evidence for exceptions. Many endometrial carcinomas are in the gray zone with overlapping clinical, morphologic, immunohistochemical, and molecular features of types I and II endometrial cancers. Finally, a small group of endometrial carcinoma is noted to be hereditary. It is known as the most common extracolonic malignancy in hereditary nonpolyposis colorectal cancer (Lynch syndrome), an autosomal dominantly inherited disorder of cancer susceptibility. Inactivation of the mismatch repair genes MSH2 and MSH6 seems to play a central role in the tumorigenesis. |
| first_indexed | 2024-12-11T01:39:54Z |
| format | Article |
| id | doaj.art-ca45a5bda8bd486492b8743284632de3 |
| institution | Directory Open Access Journal |
| issn | 1028-4559 |
| language | English |
| last_indexed | 2024-12-11T01:39:54Z |
| publishDate | 2007-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Taiwanese Journal of Obstetrics & Gynecology |
| spelling | doaj.art-ca45a5bda8bd486492b8743284632de32022-12-22T01:25:04ZengElsevierTaiwanese Journal of Obstetrics & Gynecology1028-45592007-03-01461263210.1016/S1028-4559(08)60102-3Molecular Carcinogenesis of Endometrial CancerFu-Shing LiuIn 1983, Bokhman proposed a dualistic model of endometrial tumorigenesis based on the clinical observations and clinicopathologic correlations. The majority of endometrial cancers (approximately 70–80%), designated as type I carcinomas, follow the estrogen-related pathway. Histologically, most of the type I tumors seem to arise in the background of hyperplastic endometrium, show an endometrioid differentiation, and are of low grade. Clinically, they are overall characterized by a favorable behavior. Another 10–20% of endometrial cancers, designated as type II carcinomas, follow the estrogen-unrelated pathway and arise in the background of atrophic endometrium. Type II tumors usually occur at an older age, approximately 5–10 years later than type I tumors. They are typically high-grade carcinomas of nonendometrioid differentiation, most frequently serous, less frequently clear cell. Type II carcinomas behave as an aggressive clinical course and poor prognosis. This dualistic model was subsequently supported by the molecular studies, approximately a decade later. At present, endometrioid and serous carcinoma, which represent the major phenotypes of types I and II endometrial carcinomas, respectively, are characterized by distinctive types of genetic instability and molecular alterations. In endometrioid (type I) carcinoma, four major genetic changes are responsible for the tumorigenesis, i.e. silencing of PTEN tumor suppressor gene, presence of microsatellite instability due to alterations of the mismatch repair genes, mutation of K-ras protooncogene, and alteration of β-catenin gene. On the other hand, p53 mutation and overexpression of Her2/neu oncogene are two major genetic alterations in serous and clear cell (type II) carcinomas. However, like in any model, there is evidence for exceptions. Many endometrial carcinomas are in the gray zone with overlapping clinical, morphologic, immunohistochemical, and molecular features of types I and II endometrial cancers. Finally, a small group of endometrial carcinoma is noted to be hereditary. It is known as the most common extracolonic malignancy in hereditary nonpolyposis colorectal cancer (Lynch syndrome), an autosomal dominantly inherited disorder of cancer susceptibility. Inactivation of the mismatch repair genes MSH2 and MSH6 seems to play a central role in the tumorigenesis.http://www.sciencedirect.com/science/article/pii/S1028455908601023carcinogenesisendometrial carcinomagenetic alteration |
| spellingShingle | Fu-Shing Liu Molecular Carcinogenesis of Endometrial Cancer Taiwanese Journal of Obstetrics & Gynecology carcinogenesis endometrial carcinoma genetic alteration |
| title | Molecular Carcinogenesis of Endometrial Cancer |
| title_full | Molecular Carcinogenesis of Endometrial Cancer |
| title_fullStr | Molecular Carcinogenesis of Endometrial Cancer |
| title_full_unstemmed | Molecular Carcinogenesis of Endometrial Cancer |
| title_short | Molecular Carcinogenesis of Endometrial Cancer |
| title_sort | molecular carcinogenesis of endometrial cancer |
| topic | carcinogenesis endometrial carcinoma genetic alteration |
| url | http://www.sciencedirect.com/science/article/pii/S1028455908601023 |
| work_keys_str_mv | AT fushingliu molecularcarcinogenesisofendometrialcancer |