••• Chapter 44^ Endometrial Hyperplasia and Carcinoma^445
❍ What are the risk factors associated with the development of endometrial carcinoma?
Obesity, nulliparity, early menarche, and late menopause. Women 21 to 50 pounds over ideal body weight increase
their risk of developing endometrial carcinomas threefold. Women in excess of 50 pounds over ideal body weight
increase their chance of developing endometrial carcinoma 10-fold.
❍ What is HNPCC Lynch syndrome type II?
A hereditary predisposition to the development of colon, breast, ovarian, and endometrial cancer. In approximately
one-half of cases of affected women, endometrial and ovarian cancers precede colon cancer.
❍ What is the most frequent mismatch repair gene that is associated with the accumulation of endometrial
cancer cases in HNPCC families?
MSH6
Although MSH2 and MLH1 are also associated with endometrial cancer, the highest accumulation of endometrial
cancer cases was observed in families with MSH6 mutation.
❍ Women who are at risk of HNPCC have what percentage risk of developing endometrial and ovarian
cancers?
40% to 60% risk of developing endometrial cancer and 12% risk of ovarian cancer.
❍ What other than colon, endometrial, and ovarian cancers are seen in HNPCC families?
Gastric, urologic, and small bowel cancers.
❍ The Breast Cancer Linkage Consortium reported that elevated number of endometrial cancer was due to the
mutation of which BRCA gene?
Among BRCA1 carriers, the risk of endometrial cancer was reported to be 2.6 times higher than expected
(95% CI 1.7 to 4.2). But the penetrance of BRCA1 mutations or endometrial carcinoma is low and the hereditary
fraction is small. No elevated number of endometrial carcinoma was detected due to BRCA2 mutation.
❍ What rare dominant skin disease syndrome is associated with endometrial, thyroid, and breast cancer?
Cowden syndrome. Inherited constitutional mutation of phosphatase and tensin homolog (PTEN) is the reason of
Cowden disease. Somatic mutation in PTEN is also common in endometrial cancer.
❍ Which hereditary syndrome increases the risk of endometrial cancer?
HNPCC with MHS6, MLH1, and MSH2 mismatch repair gene mutations. Women with HNPCC syndrome have a
markedly increased risk of endometrial cancer compared with women in the general population. Among women who
are HNPCC mutation carriers, the estimated cumulative incidence of endometrial cancer ranges from 20% to 60%.
Mildly increased incidence was detected with BRCA1 mutations and in Cowden syndrome (PTEN mutation).
❍ Name four medical conditions that increase the risk of developing endometrial cancer because of excess
endogenous estrogen.
(1) Women with chronic anovulation (PCO).
(2) Women with estrogen secreting ovarian neoplasms, most commonly granulosa cell and theca cell tumors.
(3) Obese postmenopausal women.
(4) Women with severe liver disease.