Why Women With Endometriosis Need to Know Their MSI Status
Thanks to recent我们对癌症生物学的理解的进步，科学家们已经确定了几种特定的分子改变，可能影响某些患者及其家庭的先进子宫内膜癌症和遗传检测。其中一个是microsatellite instability.
如果您或您所爱的人被诊断出患有子宫内膜癌，那么您需要知道的内容。
What is microsatellite instability?
身体中的每种细胞都包含DNA，其中包含您独特的遗传密码的分子。当细胞划分时，例如要生长或替换旧细胞时，您的DNA都会成为自身副本（重复）。细胞必须快速分割并复制DNA而不会产生错误。
但是，此过程中的错误很常见。
“微卫星是小型的DNA重复，更容易受损，”Ursula Matulonis, M.D.达纳弗伯癌学院苏珊F.史密斯妇女癌症妇科肿瘤科妇科肿瘤司司长。
Left unfixed, these errors can cause mutations that may eventually lead to cancer. Fortunately, your body has a mechanism for repairing these errors called mismatch repair (MMR). MMR proteins recognize and fix DNA damage after replication. Think of it as a DNA spell checker.
Sometimes, however, this system doesn’t work as well as it should. When cells are mismatch repair deficient, they are more likely to acquire DNA mutations that may lead to cancer. This results in a situation called microsatellite instability (MSI). About20 to 30 percent of women with endometrial cancer have poorly functioning MMR.
MSI可以happen at the germline level, which means it occurs throughout the body,Jessica Lee, M.D., tells HealthCentral. Dr. Lee is an assistant professor of obstetrics and gynecology at UT Southwestern Medical Center. However, says Dr. Lee, MSI can also happen just at the level of the tumor.
What MSI means for endometrial cancer patients
Microsatellite Instability has implications for endometrial cancer patients in two important ways.
林奇综合征和msi
MSI may indicate you have a genetic condition called林奇综合征. Patients with Lynch syndrome have tumors with a higher frequency of mutations. This put you at greater risk for endometrial cancers as well as other types of cancer, including colon, ovarian, gastric, hepatobiliary, urothelial, and some skin and central nervous system cancers. Roughly3 to 5 percent of all women with endometrial cancer have Lynch syndromeand are therefore predisposed to developing additional cancers.
李博士说，识别林奇综合症的人很重要。
“如果鉴定患者患有林奇综合症，这意味着他们的主要亲属有50％的机会也有林奇，”她说。“基因检测的最重要方面是找到不受影响的家庭成员[那些没有癌症的人]so we can help prevent cancer in them.”
Once you or your family members know you have Lynch syndrome, you can take steps to prevent Lynch-related cancers, or at least catch them in an early stage. Frequentcolonoscopies- 每年或两年而不是每10年 - 都会有助于预防结肠癌。常规活组织检查可以提前捕获子宫内膜癌。一旦你完成了孩子，或者在40岁到45岁之间，你可以让你的子宫和卵巢删除。“有不同的方式，我们可以监控并做干预措施，以防止人们患上癌症，”李博士说。
Matulonis博士说，当妇女被诊断出患有子宫内膜癌时，他们的肿瘤常规测试MSI。如果您是微透明技术稳定，那意味着您没有MSI，您的DNA修复过程正常运行。如果你是微透明石不稳定，那意大观你有MSI，这是一个很好的指标，你也可能有林奇综合征。
MSI and immunotherapy
Women with recurrent endometrial cancer (cancer that has come back after treatment) who have microsatellite unstable tumors may be candidates for an immunotherapy treatment called pembroluzimab (Keytruda).
“This is the first situation in which a drug was approved not for a specific tumor, but for a specific genetic event,” says Dr. Matulonis.
There is still a lot to learn about which patients will benefit most from pembroluzimab, Dr. Matulonis says. It’s also important to balance the potential benefits against the potential harms, which are not insignificant. The most common toxicities of permbroluzimab include pneumonitis; colitis; skin rashes; glandular problems, such as hypothyroidism or even diabetes; and liver toxicities, including hepatitis. Furthermore, the drugs are costly, so oncologists want to be sure they’re using them appropriately.
The bottom line
子宫内膜癌是全世界妇女中最普遍的妇科癌症, and the incidence is increasing.Abnormal vaginal bleedingis the hallmark symptom of endometrial cancer. If you have any bleeding in menopause, excessive bleeding during periods, or unusually frequent periods, seek medical attention. And, if you have a strong family history of cancers that might indicate Lynch syndrome, ask your doctor about genetic testing.
