Most practicing gynecologists will diagnose a patient with endometrial cancer at some point during their careers. While referral to a gynecologic oncologist is indicated for treatment of all endometrial cancers, patients will likely have questions for their gynecologists prior to referral. The backbone of prognosis and treatment depends on the type of endometrial cancer (type 1 or type 2) and the stage of the cancer. The basics of endometrial cancer treatment will be reviewed in this article.

Endometrial cancer can be classified into two distinct subgroups based on histology and clinical behavior. Type 1 tumors are the most common type of endometrial cancer, accounting for nearly 80% of endometrial cancers. These tumors have an endometrioid histology and are well-differentiated, gland-forming tumors. The endometrioid tumors are graded by evaluating the gland formation and/or architecture, with grade 1 tumors having less than 5% solid growth and grade 2 tumors having 6%-50% solid growth. They also are graded based on the degree of nuclear atypia ( Gynecol. Oncol. 1983;15:10-17 ).

Type 1 tumors are estrogen driven and less aggressive than their type 2 counterparts. They tend to be more common in overweight or obese patients, patients with longstanding anovulation or polycystic ovarian syndrome (PCOS), or patients placed on unopposed estrogen. Molecularly, type 1 tumors often exhibit mutations in phosphatase and tensin homolog (PTEN), Kras, and beta-catenin. Microsatellite instability with mutations in MSH2, MSH6, MLH1, and PMS2 also has been observed in 20% of sporadic endometrial cancers, as well as women with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome) ( J. Clin. Oncol. 2006;24:4783-91 ).

Type 1 tumors are starkly different from type 2 tumors. While type 2 tumors account for 10%-20% of endometrial cancers, they are responsible for the majority of recurrences and deaths. They include serous, clear cell, mucinous, squamous, transitional cell, carcinosarcomas and undifferentiated tumors. More recently, it has been suggested that grade 3 endometrioid carcinomas be grouped with type 2 tumors. The genetic mutations and clinical behavior of grade 3 endometrioid tumors are more consistent with type 2 tumors. Type 2 tumors are more likely to show mutations in p53, aneuploidy, and overexpression of HER2/neu ( Gynecol. Oncol. 2008;108:3-9 ). Type 2 tumors are more likely to present with advanced stage.

While it is important to understand these two categories of endometrial cancers as two distinct clinical entities with markedly different prognosis and outcomes, there is some histologic crossover. Some endometrioid tumors will have a component of serous or clear cell within the tumor. Investigators have found that up to a 10% serous component within an endometrioid tumor can confer a worse prognosis and likely warrants more aggressive treatment ( Cancer 2004;101:2214-21 ).

Given the relatively indolent clinical course of type 1 tumors, preoperative imaging to evaluate for metastatic disease is not indicated without concerning symptoms. Additionally, often women diagnosed with type 1 tumors are able to be fully treated with hysterectomy, and in circumstances of early-stage disease, most patients with these tumors do not need adjuvant treatment with chemotherapy or radiation. Alternatively, type 2 tumors are more aggressive and may warrant additional imaging prior to hysterectomy to evaluate for distant metastasis, as uterine features may not be indicative of metastatic disease. These women will need additional treatment with radiation and likely chemotherapy following comprehensive surgical staging and hysterectomy, given the aggressive nature of their tumors.

Dividing endometrial cancers into these two distinct groups allows providers to appropriately counsel and treat patients. Having an understanding of this distinction can help practicing gynecologists who will most likely make the diagnosis of endometrial cancer within their practice. Any patient with abnormal bleeding or postmenopausal bleeding should be promptly evaluated to facilitate an early diagnosis. Regardless of whether a patient has a type 1 or type 2 tumor, early-stage diagnosis will improve the patient’s prognosis and survival.

Dr. Clark is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Clark and Dr. Gehrig had no conflicts of interest to disclose.

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