Endometrial Carcinoma In Women Research Articles

Endometrial cancer in women 45 years of age or younger: A clinicopathological analysis

The purpose of this study was to evaluate the experience with endometrial carcinoma in women < or =45 years of age at Ochsner Clinic Foundation, New Orleans, La. We evaluated the clinical history, treatment, and follow-up of 38 women < or =45 years of age diagnosed with endometrial cancer. Thirty-eight patients received primary treatment for endometrial cancer: stage I, 32 (84.2%); stage II, 1 (2.6%); stage III, 4 (10.5%); stage IV, 1 (2.6%). Tumors were well differentiated in 20 (52.6%), moderately differentiated in 10 (26.3%), and poorly differentiated in 8 (21.1%). At end of study period 32 women (84.2%) were alive with no evidence of disease, 5 had died of recurrent disease, and 1 died of metastatic breast cancer. Patients < or =45 years of age had lower incidence of advanced stage disease, higher degree of tumor differentiation, and better prognosis compared to patients older than 45 years.

Pathologic diagnosis of endometrial carcinoma in curettage specimens in women under forty years of age

To investigate the diagnostic pathological features of endometrial carcinomas present in women under 40 years of age (by curettage samples). A retrospective analysis was performed on 20 cases of endometrial carcinomas in women under 40 years of age. The patients included 18 endometrioid adenocarcinoma cases, one adenosquamous carcinoma case, and one papillary serous carcinoma case. The morphological features of the endometrial adenocarcinoaare loss of polarity (orientation) of the endometrial glands. The tumor cells have large round vesicular nuclei, prominent nucleoli and coarse chromatin. In addition, endometrial stroma was instead of by the fibrous and/or granulation tissue type stroma, usually with inflammatory response. Majority cases of endometrioid adenocarcinomas had superficial invasion of myometrium and no lymph node metastasis. The adenosquamous case metastasized to the ovaries and the papillary serous carcinoma case metastasized to the pelvic lymph nodes. Endometrial carcinomas which are highly differentiated endometrioid adenocarcinomas occur frequently in women under 40 years of age. An important differential diagnosis of the endometrioid carcinoma in a curettage specimen is to differentiate it from atypical endometrial hyperplasia and atypical polypoid adenomyoma.

Assessment of the quality and frequency of mutations occurrence in PTEN gene in endometrial carcinomas and hyperplasias

The quality and frequency of mutations in PTEN gene were assessed in 59 carcinomas and 6 hyperplasias of the endometrium in women. Screening for mutations was done in all exons of PTEN gene by the PCR-SSCP analysis and DNA sequencing. Results were correlated with histological status and clinical features of endometrial carcinomas. In 45.8% (27/59) of carcinomas, 36 somatic mutations were detected in PTEN gene. In seven carcinomas, two mutations and in one carcinoma three mutations coexisted simultaneously. Moreover in 33.3% (2/6) of hyperplasia cases mutations were shown. Most identified mutations (57.9%) were present in exons 5 and 8, less frequently in exons 2 (15.8%) and 7 (13.2%) and they were least frequent in exons 1 and 3 (5.3% each). No mutations were found in exons 4, 6 and 9. Of all identified mutations, 73.7% of those resulting in truncated protein were present due to deletions, insertions and nonsense mutations. Missense mutations accounted for 13.2% of mutations and they were present only in exon 5. One point mutation (2.5%) was in intronic splice site. The remaining 10.5% of mutations were neutral polymorphisms. No statistically significant correlation were found between the frequency of PTEN gene mutations and the clinical stage of endometrial carcinomas. However, evident statistically significant, reverse correlation were observed between the frequency of mutations and the grade of morphological differentiation of the diseases ( χ 2=7.2393, α=0.0071). In conclusion, our data support the view that PTEN gene mutations are frequent events involved in development of endometrial carcinomas in women.

Risk of Endometrial Carcinoma Associated With BRCA Mutation

Abstract Objective. Inherited mutations in the BRCA1 or BRCA2 genes are associated with a greatly increased lifetime risk of breast and ovarian cancers and a modestly increased risk of several other cancer types. Several case reports of endometrial carcinoma in women with a BRCA mutation have led to speculation regarding the effect of these genes on the risk of endometrial cancer. The purpose of this study was to test the hypothesis that germline mutation of a BRCA gene is associated with an increased risk of endometrial carcinoma. Methods. A retrospective cohort of 199 consecutive Ashkenazi Jewish patients with endometrial carcinoma was identified from a 12-year period at this institution. All were genotyped for the three BRCA founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 ) that exist in this population, and the case frequency was compared to the known population frequency of these mutations. Additionally, endometrial carcinomas occurring in patients with BRCA mutations were assessed for somatic loss of the wild-type BRCA allele. Results. Germline BRCA mutations were identified in 3 (1 in BRCA1 and two in BRCA2 ) of 199 (1.5%) patients, compared to a frequency of 2.0% in this population generally. A relative risk of endometrial carcinoma associated with BRCA mutation, as estimated by the odds ratio, was calculated as 0.75 (95% CI=0.24–2.34; P = 0.6). Loss of the wild-type BRCA allele was observed in two of three tumors associated with a BRCA mutation. Conclusions. For individuals with a germline BRCA mutation, the lifetime risk of endometrial carcinoma is not increased.

Risk of Endometrial Carcinoma Associated with BRCA Mutation

Objective.Inherited mutations in the BRCA1 or BRCA2 genes are associated with a greatly increased lifetime risk of breast and ovarian cancers and a modestly increased risk of several other cancer types. Several case reports of endometrial carcinoma in women with a BRCA mutation have led to speculation regarding the effect of these genes on the risk of endometrial cancer. The purpose of this study was to test the hypothesis that germline mutation of a BRCA gene is associated with an increased risk of endometrial carcinoma.Methods. A retrospective cohort of 199 consecutive Ashkenazi Jewish patients with endometrial carcinoma was identified from a 12-year period at this institution. All were genotyped for the three BRCA founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2) that exist in this population, and the case frequency was compared to the known population frequency of these mutations. Additionally, endometrial carcinomas occurring in patients with BRCA mutations were assessed for somatic loss of the wild-type BRCA allele.Results. Germline BRCA mutations were identified in 3 (1 in BRCA1 and two in BRCA2) of 199 (1.5%) patients, compared to a frequency of 2.0% in this population generally. A relative risk of endometrial carcinoma associated with BRCA mutation, as estimated by the odds ratio, was calculated as 0.75 (95% CI = 0.24–2.34; P = 0.6). Loss of the wild-type BRCA allele was observed in two of three tumors associated with a BRCA mutation.Conclusions. For individuals with a germline BRCA mutation, the lifetime risk of endometrial carcinoma is not increased.

Endometrial carcinoma in women under 40 years of age: incidence of ovarian carcinoma and ovarian metastasis

Background. Patients under 40 years of age with endometrial carcinoma were compared with patients aged 40 years or more in terms of clinical and histopathological characteristics.

Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen.

Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice.

Endometrial Carcinoma in Elderly Women

Endometrial carcinoma remains the most common invasive gynecologic malignancy. Increased longevity is associated with an increased incidence of endometrial carcinoma (EC) in elderly women. While recent studies have looked at aging and its relation to ovarian, breast, and cervical cancer, few have focused on EC in the growing elderly population. This study analyzed 35 histologic specimens of EC in women 75-92 years of age. Findings revealed that only 23% of the tumors were Stage I, G1. The majority (77%) were deeply invasive or of advanced stage (IC-IV). These were G2, G3, or "virulent" types of nonendometrioid EC (undifferentiated, clear cell, uterine serious papillary, and squamous cell carcinoma). Fifty-seven percent of tumors were endometrioid, of which 9% were mixed, including a rare case of nongestational choriocarcinoma. The nonendometrioid tumors, compared to the endometrioid types, were more often high-stage tumors with vascular invasion. They were also more often associated with atrophic (vs hyperplastic) uninvolved endometrium. Clinical risk factors (nulliparity, obesity, estrogen replacement therapy) were assessed and correlated with the histologic findings. It was shown that tumors in the elderly were less likely to be estrogen-related. It was concluded that EC in this age group is more aggressive, histologically less differentiated, and often nonendometrioid compared with EC in the general population. The increased virulence of EC in the elderly may be related to the tumor's independence from hormonal factors, to the poorly understood but well-known diminished immunologic defense against cancer in general in elderly patients, and/or to the belated diagnosis of the disease in this population.

Endometrial cancer in premenopausal women 45 years and younger

To evaluate the experience with endometrial carcinoma in women 45 years or younger at the Royal Hospital for Women, Sydney, Australia. We evaluated the clinical history, morphology, treatment, and follow-up of 17 premenopausal women 45 years or younger who had been diagnosed with endometrial cancer. All histopathology was reviewed. Sixteen patients received their primary treatment at the Royal Hospital for Women, and one was referred with recurrent disease. Synchronous ovarian malignancies were found in five of 17 cases (29.4%), compared with 11 of 237 (4.6%) women older than 45 (P < .001). Three other patients had secondary ovarian involvement. Five (29%) patients had stage III or IV disease. Thirteen (76.5%) women were alive with no evidence of disease 12-78 months after primary surgery; two were lost to follow-up, but had no evidence of disease at 21 and 29 months, respectively. Two women died of recurrent disease. All but two patients with stage IV disease receiving primary treatment at the Royal Hospital for Women were offered hormone replacement therapy on discharge from the hospital. Ovarian and lymph node involvement were common in women 45 years and younger with endometrial cancer. Hormone replacement therapy did not appear to compromise survival.

Endometrial Carcinoma in BD II/Han Rats: Model of a Spontaneous Hormone-Dependent Tumor

The incidence of endometrial carcinomas as well as the life-spans of 5 groups of female BD II/Han inbred rats were compared. Groups compared were control (CON), ovariectomized (OV), retired breeder (RB), germfree rats (GF), and rats fed a purified diet (PD). Carcinomas, for the most part adenocarcinomas, occurred in 90% of the CON and PD rats and approximately 60% of the RB and GF rats. Carcinomas did not develop in OV rats. The mean life-span of the CON and PD rats was 22 months. The RB and GF rats reached, respectively, 32 and 30 months; and the OV rats, 39 months. An essential influence of ovarian hormones on tumorigenesis was shown. Alimentary carcinogens and phytoestrogens, as well as chronic irritations of the endometrium due to bacteriologic inflammations, could be excluded as tumor initiators. Hormonal dysregulation in the aging BD II/Han rats was discussed as a possible cause of an inappropriate stimulation of the endometrium, promoting a previously transformed tumor cell or initiating an autonomous tumor growth. Such evidence supports the use of the BD II/Han rat as a suitable model for the study of hormonal effects on the tumorigenesis of endometrial carcinomas in women.

Extraadrenal formation of a mineralocorticosteroid: deoxycorticosterone and deoxycorticosterone sulfate biosynthesis and metabolism.

EXTRAGLANDULAR steroid hormone formation is now established as a physiological as well as a pathophysiological phenomenon in men, women, and children (1–8). Indeed, it has been demonstrated that most, if not all, estrogen formed in children (9, 10), men (1, 6, 11, 12), and anovulatory (13–15) and postmenopausal (1, 12, 13, 16–21) women arises by the extraglandular aromatization of plasma C19-steroids. Greater than normal extraglandular estrogen formation can give rise to feminization in men (1, 3–6, 8, 9, 22–25) and to uterine bleeding (1, 13–15, 17, 19, 21, 26, 27) and possibly to endometrial carcinoma in women (17, 19, 21, 26). It also is known that the biologically potent androgen testosterone can be produced in extraglandular tissues from circulating precursors (28–33). In fact, most of the testosterone produced in young women arises by this mechanism (28, 29, 31, 32). In addition to the extraglandular formation of biologically active steroid hormones, it now is known that potent steroid hormones are ...

Letter: Postmenopausal estrogen therapy.

ABSTRACT To the Editor.— I wish to add a comment to the useful letter of Marshall (227:76, 1974). Dr. Marshall repeats oft-quoted statistics to the effect that 30% of patients receiving postmenopausal estrogen therapy develop uterine bleeding, and that approximately 5% to 8% of these women will be found to have endometrial carcinoma. Simple calculations indicate that these figures are rank nonsense. Conjugated estrogens occupy a place in the first half dozen drugs in order of sales volume. Since most of this medication is used by postmenopausal women, there is little question that millions of women at any one time are using postmenopausal estrogen therapy. If 30% of these patients develop bleeding, and 5% to 8% have carcinoma, this represents an incidence of 1.5% to 2.4% endometrial carcinoma in women receiving these estrogens. This would mean 15,000 to nearly 24,000 cases of endometrial carcinoma per million women taking these drugs—an epidemic