Prognostic importance of DNA ploidy and DNA index in stage I and II endometrioid adenocarcinoma of the endometrium.

BACKGROUND: We evaluated the prognostic importance of DNA ploidy in stage I and II endometrioid adenocarcinoma (EAC) of the endometrium with a focus on DNA index. PATIENTS AND METHODS: High-resolution DNA ploidy analysis was carried out in tumor material from 937 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage I and II EAC of the endometrium. RESULTS: Patients with diploid (N = 728), aneuploid tumor with DNA index ≤ 1.20 (N = 118), aneuploid tumors with DNA index >1.20 (N = 39) and tetraploid tumor (N = 52) had 5-year recurrence rates 8%, 14%, 20% and 12%, respectively. Patients with aneuploid tumor with DNA index >1.20 had a poorer 5-year progression-free survival (67%) and overall survival (72%) compared with the patients with aneuploid tumor with DNA index ≤ 1.20 (81% and 89%, respectively). Aneuploid tumors with DNA index ≤ 1.20 relapsed mainly in the vagina and pelvis, whereas aneuploid tumors with DNA index >1.20 relapsed predominantly outside pelvis. CONCLUSIONS: The recurrence risk for the patients with aneuploid tumor is higher than the patients with diploid tumor in EAC of the endometrium. Based on DNA index with cut-off 1.20, aneuploid tumors can be separated into two subgroups with different recurrence pattern and survival.

The prognostic value of DNA ploidy in a total population of uterine sarcomas.

BACKGROUND: The diagnosis of uterine sarcoma is associated with poor outcome for the patient and there is a need for reliable prognostic markers. Most previous studies on the prognostic value of DNA ploidy include few uterine sarcomas and report conflicting results. MATERIALS AND METHODS: We examined the prognostic value of DNA ploidy and its association with clinicopathological parameters and crude survival in a total population of 354 sarcoma. RESULTS: In univariate analyses, we observed significantly better crude survival for endometrial stromal sarcomas (ESS) and adenosarcoma (AS) patients with diploid as compared with nondiploid tumors, but not for patients with leiomyosarcomas (LMS). In Cox multivariate analyses, DNA ploidy was the only significant predictor of survival for patients with AS. In LMS, mitotic index (MI), tumor size, tumor extent and tumor margins, whereas for ESS, MI, tumor extent and tumor necrosis obtained independent significance of survival. DNA ploidy was a significant predictor of survival for LMS patients in Cox regression analyses when excluding MI. CONCLUSION: DNA ploidy might be useful as a prognostic marker in patients with LMS and AS.

Diagnosis and treatment of borderline ovarian neoplasms "the state of the art".

The 5-year survival for women with Stage-I borderline tumours (BOT) is favourable, about 95-97%, but the 10-year survival is only between 70 and 95%, caused by late recurrence. The 5-year survival for Stage II-III patients is 65-87%. Standard primary surgery includes bilateral SOEB, omentectomy, peritoneal washing and multiple biopsies. Second cytoreductive surgery is recommended for patients with recurrent disease. Adjuvant postoperative therapy is not indicated in Stage-I diploid tumors. Occasional responses to chemotherapy have been reported in advanced BOTs but no study has shown improved survival. Recently a new theory has been developed describing a subset of S-ovarian cyst adenomas that evolve through S-BOT to low-grade carcinoma. A more correct staging procedure, classification of true serous implants and agreement on the contribution to stage of the presence of gelatinous ascites in mucinous tumours may in the future change the distribution of stage and survival data by stage for women with BOT. Independent prognostic factors in patients with epithelial ovarian BOT without residual tumour after primary surgery are DNA-ploidy, international FIGO-stage, histologic type and patient age. Studies on other molecular markers have not yet uncovered a reliable prediction of biologic behaviour, however, there is hope that future studies of genetics and molecular biology of these tumours will lead to useful laboratory tests. Future questions to be addressed in this review include the following: Have patients with borderline tumours in general been over-treated and how should these patients be treated? How to define the high-risk patients? In which group of patients is fertility-sparing surgery advisable and, do patients with borderline tumours benefit from adjuvant treatment?

Robotic-assisted laparoscopic radical hysterectomy (Piver type III) with pelvic node dissection--case report.

OBJECTIVE: The aim of this study was to describe the first robotic-assisted radical hysterectomy (Piver type III) and bilateral pelvic lymph node dissection for a patient with Stage Ib1 cervical carcinoma. CASE: A 43-year-old woman G1, P1, previously operated on due to endometriosis with removal of the left ovary and fallopian tube, came under our care. In addition, hysteroscopic myomectomy had been done two years before. Otherwise the patient was healthy. Preoperative conization histology revealed 6 mm of stromal infiltration. The patient was offered the da Vinci robotic Wertheim operation for the first time which was well accepted and she was discharged uneventfully on the 4th day postoperatively. Four months later at a routine check-up we found asymptomatic bilateral lymphocysts but otherwise normal status. CONCLUSION: It is fully possible to perform Piver type III laparoscopic radical hysterectomy using the da Vinci robotic system and it seems that radical dissection is much more precise than the conventional laparoscopic radical hysterectomy.

A new approach to treatment of early-stage cervical carcinoma: entire laparoscopic abdominal radical hysterectomy with bilateral pelvic lymphadenectomy without vaginal cuff closure--case reports.

OBJECTIVE: The objective of this study is to describe a new technique of laparoscopic radical hysterectomy without vaginal cuff closure. METHODS: Three patients underwent laparoscopic radical hysterectomy, bilateral salpingo-oophorectomy and bilateral pelvic lymph node dissection using an Argon Beam Coagulator. Four trocars were used: umbilical port for the camera, two ports for the operating surgeon and a fourth port for use by the surgical assistant. RESULTS: All patients were clinically staged IB1. Ages were 53, 64 and 58 and BMI was 19.5, 25.2 and 21.4, respectively. Duration of surgery was 375, 325 and 335 minutes, respectively, from first trocar insertion to last closing stitch. Estimated blood loss was 300, 100 and 400 ml and removed pelvic lymph nodes 18, 15 and 26, respectively. The patients tolerated the surgical technique and recovered satisfactorily. CONCLUSION: These are the first three cases of early-stage cervical carcinoma patients who have been treated with entirely laparoscopic abdominal radical hysterectomy (LARH) and bilateral pelvic lymphadenectomy (BPL) without vaginal cuff closure. To our knowledge, this has not been previously described in the literature. It is feasible and was well tolerated in this small series of patients.

DNA copy number changes in malignant ovarian germ cell tumors.

Malignant ovarian germ cell tumors (OGCTs) include immature teratomas (ITs), dysgerminomas (DGs), endodermal sinus tumors (ESTs), choriocarcinomas, and embryonal carcinomas. Knowledge about the genetic changes associated with malignant OGCT development is sparse. We therefore analyzed 25 OGCTs (12 DGs, 4 ESTs, and 9 ITs) for gains and losses by comparative genomic hybridization. In total, more gains than losses were observed, and the number of alterations ranged from 0-20 per tumor. The average number of changes among DGs, ESTs, and ITs was 10, 6, and 1.4, respectively. The most common changes in DGs were gains from chromosome arms 1p (33%), 6p (33%), 12p (67%), 12q (75%), 15q (42%), 20q (50%), 21q (67%), and 22q (58%); gains of the whole of chromosomes 7 (42%), 8 (42%), 17 (42%), and 19 (50%); and losses from 13q (58%). Two of three DGs with a gonadoblastoma component showed gains of 3p21 and loss of 5p, whereas none of the nine pure DGs had these changes, suggesting that they might be characteristic either of gonadoblastoma or of DG developing from a gonadoblastoma. Gain of 12p and gain from 1q were seen in three of four ESTs, whereas gains from 3p, 11q, and Xp and loss from 18q were each found in two tumors. Five of the ITs revealed changes (range, 1-4 changes/tumor), with gains from 1p, 16p, 19, and 22q each being found in two tumors. We conclude that ovarian DGs and ESTs seem to develop via the same genetic pathways that are already known for testicular germ cell tumors. On the other hand, ITs do not exhibit gain of 12p and also typically show fewer changes than other malignant OGCTs, indicating that they arise via different pathogenetic mechanisms.

Early detection of familial ovarian cancer.

When ovarian cancer is detected at an early stage, prognosis is good, which has led to discussion of a screening programme. The aim of this study was to identify and examine women at high risk of familial ovarian cancer, and to evaluate the inclusion criteria and the diagnostic methods for early detection of ovarian cancer. We report the first round screening findings in a prospective study of 180 women (mean age 43.4 years) considered to be at high risk of ovarian cancer based on family history. They were subjected to gynaecological examination with transvaginal ultrasound (TVU), CA125 and breast examination. Of these, 13 women with oestrogen receptor positive breast cancer had therapeutic oophorectomy and the ovaries were histologically examined. Among 180 women examined, nine ovarian cancers (among them two found at oophorectomy because of breast cancer) (mean age 49.0 years), seven benign tumours of the ovary (mean age 48.1 years), one cancer of the cervix, and four breast cancers were diagnosed. The prevalence of ovarian cancers (5%) was significantly more than in any previous series. TVU as a diagnostic method proved useful and detected 7/9 cancers, whereas CA125 was elevated in 4/9 cancers. To our knowledge, this is the first programme which has successfully delineated a high risk group and prospectively demonstrated their high prevalence of ovarian cancer. Possible biases are discussed.

Human papilloma virus has no prognostic significance in cervical carcinoma.

The prognostic significance of the detection of HPV (human papilloma virus) DNA in cervical carcinoma was evaluated in 223 cases treated from January 1988 to November 1989. HPV DNA was detected by PCR (polymerase chain reaction) on fresh tumour specimens obtained before therapy was started. HPV DNA of any type was detected in 93.3% of all tumours, HPV16 was the predominant type and was detected in 69% of cases. HPV18 was more frequent in adeno- and adenosquamous carcinoma than in squamous cell carcinoma and occurred more often in poorly differentiated tumours than in more highly differentiated tumours. Patients with HPV negative tumours were on average older than patients with tumours containing HPV. Neither presence of HPV DNA nor HPV type had prognostic significance. In 63 women with early stage tumours submitted to surgery, no difference was found in the frequency of lymph node metastasis, vessel invasion or prognosis related to HPV type. We conclude that neither the presence nor the type of HPV DNA had any prognostic significance in cervical carcinoma.

Prognostic value of pre- and postoperative serum CA 125 levels in ovarian cancer: new aspects and multivariate analysis.

The prognostic significance of the serum CA 125 level was studied in 687 patients with invasive epithelial ovarian malignancies. The samples were collected preoperatively in 200 and postoperatively in 487 patients. Median follow-up was 27 months (range 3-84). The serum CA 125 level was elevated preoperatively in 90% of cases, with a median value of 429 U/mL. In patients with evidence of disease at the time of sampling, the CA 125 serum level correlated directly to tumor stage, tumor load, and histologic grade. Using Cox multivariate analysis, the preoperative serum CA 125 level had no independent prognostic significance, whereas the postoperative level did. In patients without residual disease after primary surgery, histologic type (P less than .0001), postoperative CA 125 level with 35 U/mL as the cutoff value (P = .0009), and tumor grade (P = .034) were independent prognostic factors for survival. For those with residual tumor after primary surgery, histologic type (P less than .0001), postoperative treatment (P = .0002), size of residual disease (P = .0005), and postoperative serum CA 125 level with 65 U/mL as a cutoff (P = .003) were independent prognostic factors.

Karyotypic findings in tumors of the vulva and vagina.

Neoplasms of the vulva and vagina together account for less than 5% of all female genital tract cancers, and very few cases have been analyzed using chromosome banding techniques. We report the karyotypic findings in a consecutive series of ten tumors of the vulva and vagina; in addition to five squamous cell carcinomas of the vulva, we present the first cytogenetic analysis of two malignant melanomas and a Paget disease of the vulva, as well as an adenocarcinoma and a squamous cell hyperplasia of the vagina. Whereas no clonal karyotypic changes were found in the squamous cell hyperplasia of the vagina, the remaining nine malignant tumors showed clonal chromosome abnormalities. An inverse correlation was found between the degree of histologic differentiation and karyotypic complexity in the squamous cell carcinomas of the vulva. The malignant melanomas had chromosomal aberrations that have previously been described in malignant melanomas occurring elsewhere, but were less karyotypically complex. Cytogenetically unrelated clones were detected in the Paget disease of the vulva but not in any of the other tumors; this finding is consonant with the interpretation that at least a proportion of Paget disease of the vulva arises multicentrically within the epidermis from pluripotent stem cells.

The invasive front of carcinomas. The most important area for tumour prognosis?

Various molecular events of importance in tumour spread, like the gain and loss of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation, and the initiation of angiogenesis occur at the tumour-host interface (invasive front). We have hypothesised that molecular or morphological characteristics at the invasive front area of various carcinomas may reflect tumour prognosis better than other parts of the tumour. Consequently, we recently developed a simple malignancy grading system restricted to the deep invasive front area of head and neck squamous cell carcinomas. This grading system proved to have additional prognostic value over the established prognostic factors. All similar studies performed so far have confirmed the high prognostic significance of the invasive front grading in squamous cell carcinomas at different locations. In this review paper we describe the system and the hypothesis on which it has been developed. The reproducibility of the grading is acceptable for further extended studies. Interestingly, observations of similar invasive front alterations in different adenocarcinomas suggest that the invasive tumour front may underlie the biological aggressiveness of carcinomas of glandular origin, as well.

Clear-cell and papillary serous cancer: treatment options.

Clear-cell carcinoma (CCC) and serous papillary carcinoma of the endometrium (UPSC) are rare subtypes of endometrial carcinoma (10%). The histological diagnosis can be made on the dilation and curettage specimens in both types in a very high percentage of the cases. This is important in the planning of treatment. CCC and UPSC are associated with about 50% of all relapses occurring in endometrial carcinoma, and the 5-year survival rate is, on average, 42% and 27% respectively. Surgico-pathological stage, age, and vessel invasion are independent prognostic factors for both groups. The recurrence rate is extremely high, and the most frequent extra-pelvic sites of relapse are the upper abdomen, lungs and liver. Stage Ia patients treated with complete surgical staging alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. The treatment of patients with CCC and UPSC stage Ib, Ic, II and III should include radical debulking surgery and some form of adjuvant therapy, but it is not clear which type is most effective. Adjuvant pelvic radiotherapy plus intracavitary radiotherapy is usually given in early-stage disease and pelvic radio therapy/or whole abdomen irradiation plus adjuvant systemic chemotherapy (PAC) in advanced disease. However, we are urgently waiting for a large prospective randomized study to compare both modalities. Paclitaxel, alone or in combination, is currently being tested in phase II studies.

Carcinoma of the endometrium in Norway: a histopathological and prognostic survey of a total population.

In a histopathological review of a total population, 1974 cases of endometrial carcinoma were found from 1970 to 1977. Of these 1566 (79.3%) were adenocarcinomas of the endometrioid type, 181 (9.2%) adenoacanthomas, 97 (4.9%) clear cell carcinomas, 74 (3.7%) adenosquamous carcinomas, 31 (1.6%) undifferentiated carcinomas, 22 (1.1%) serous papillary carcinomas and 3 (0.1%) squamous cell carcinomas. Thirty percent of the tumors were well differentiated, 44% moderately and 25.9% poorly differentiated. The mean age at diagnosis was 62.0 years (range 32-93 years). Age was clearly related to histologic type, grade and extent of myometrial infiltration. Crude 5- and 10-year survival rates for the entire group were 73.1 and 61%. For the different subtypes of endometrial carcinoma the 5- and 10-year crude survival rates were as follows: adenoacanthoma 91.2 and 79.6%, adenocarcinoma of the endometrioid type 74.1 and 62.2%, adenosquamous carcinoma 64.9 and 52.7%, undifferentiated carcinoma 58 and 48%, clear cell carcinoma 42.3 and 30.9% and serous papillary carcinoma 27 and 14%. All three patients with squamous cell carcinoma died within a year. The 5- and 10-year survival rates were 87.8 and 79.7% for grade 1 tumors, 76.6 and 62.1% for grade 2, and 60.1 and 48.6% for grade 3. The extent of myometrial infiltration was a string predictor of prognosis. The 5- and 10-year survival rates of patients with intramucosal tumors and tumors infiltrating the inner half of the myometrium were, respectively 89.6 and 82.5%, and 84.7 and 72.7%. Only 48.3 and 29.3% of the patients with tumors reaching the serosa survived, respectively 5 and 10 years. Patients without demonstrable vessel invasion had a significantly better prognosis than those with vessel invasion with a survival rate of 83.5 and 61.1% at 5- and 10-years, compared with 64.5 and 53.8%, respectively. Age at the time of diagnosis was an important prognostic factor for crude survival. Surgico-pathological staging was significantly better than clinical staging in predicting prognosis only in advanced stages.

DNA ploidy; the most important prognostic factor in patients with borderline tumors of the ovary.

The prognostic significance of DNA ploidy in relation to clinical and histopathologic factors was evaluated in a retrospective study of 370 patients treated at the Norwegian Radium Hospital from 1970 to 1982 with complete follow-up of median 149 months. Evaluable flow cytometric DNA histograms from paraffin-embedded tissue from the primary tumor were obtained in 321 cases, 293 (91%) were diploid and 28 (9%) were aneuploid. Aneuploidy was associated with older age, more advanced disease and non-serous histologic types. By multivariate analysis the only parameters with prognostic significance for corrected survival (death from disease) were ploidy, stage, histologic type and age. The patients with aneuploid tumors had a 19-fold increased risk of dying of disease compared with patients with diploid tumors. In tumor-free operated patients the extent of surgery had no influence on survival, neither had postoperative treatment. Using the prognostic factors the patients could be divided into risk groups. The large group of patients with diploid stage I tumors belonged to the low risk group. Fertility-saving operations can be offered to patients with diploid stage IA tumors, all others should have bilateral salpingo-oophorectomy and omentectomy with or without hysterectomy. Patients with diploid stage I tumors should not receive adjuvant treatment. The value of adjuvant chemotherapy in the high risk group needs further investigation.

Influence of HSP27 and steroid receptor status on provera sensitivity, DNA-ploidy and survival of females with endometrial cancer.

Heat shock protein (HSP) 27, estradiol (ER), progesterone (PR), isocitric dehydrogenase and DNA-ploidy have been measured in 152 endometrial adenocarcinomas. These parameters have also been related to each other and to tumor grade and overall patient survival. HSP27 was assessed immunohistochemically and ploidy by FACS analysis, whilst biochemical methods were used for the other assays. HSP27 was significantly correlated with ER but not PR, grade or ploidy. Both ER and PR were related to tumor grade but not ploidy. Provera (2-14 days, mean 8) had no apparent effect on HSP27 staining but induced isocitric dehydrogenase in 70% of the tumors. Provera decreased ER (64%) and PR (70%) content in originally positive tumors. The presence of either HSP27, ER or PR in the pretreatment sample was significantly associated with provera induction of isocitric dehydrogenase activity; neither tumor grade nor ploidy predicted for induction of this enzyme. High levels of either HSP27, ER, PR or provera-induced isocitric dehydrogenase and diploid DNA were associated with good overall survival, whereas aneuploidy was linked with poor survival.

Rates of regression and progression of dysplastic lesions in the nasal mucosa in nickel workers: a Markov model approach.

Nasal epithelial dysplasia is considered a precancerous state. From 1976 through 1989, regular screening for such lesions has been performed among workers at the Falconbridge nickel refinery in Kristiansand. The longitudinal data thus obtained have been evaluated to ascertain to what extent, if any, pre-existing dysplasia can regress when exposure to nickel is reduced. A total of 418 pairs of observations were available from 243 workers. Interpretation of the data is complicated by the fact that dysplasia may remain undetected in small biopsies and the probability of detection of existing dysplasia was, therefore, incorporated into the two-state Markov model. Transition probability rates were estimated by maximum likelihood. The results suggest that regression of dysplasia has taken place and that regression rates increased with time. This finding probably reflects a decreased exposure resulting from a combination of a reduction in airborne nickel, improved personal hygiene and allocation of workers with dysplasia to work in areas with lower nickel exposure. Our results indicate that the chance of developing carcinomas related to nickel exposure is reduced. There are, however, indications that dysplasias continue to develop at a low rate.

Novel epigenetically deregulated genes in testicular cancer include homeobox genes and SCGB3A1 (HIN-1).

Testicular germ cell tumours (TGCTs) are classified into two main histological subgroups: seminomas and non-seminomas. The latter comprise several subtypes: embryonal carcinomas, yolk sac tumours, choriocarcinomas, and teratomas. These embryonal and extra-embryonal-like differentiation lineages represent a caricature of early normal development, and inactivation of gene expression through promoter hypermethylation may therefore be of particular importance in germ cell tumourigenesis. The promoter methylation status of ten candidate genes-CDH13, DLX6, EMX2, HOXA9, HOXB5, MSX1, MSX2, RASSF1A, RUNX3, and SCGB3A1 (alias HIN-1)-was assessed by methylation-specific PCR in seven intratubular germ cell neoplasias and 55 primary TGCTs. Furthermore, by a discovery-based global approach, comparing cDNA microarray expression profiles of two germ cell tumour cell lines before and after treatment with the demethylating agent 5-aza-2'-deoxycytidine, a gene list of potentially epigenetic targets was identified, from which CGGBP1, CGRRF1, SMARCC2, SORBS1, and XPA were analysed further. Overall, the non-seminomas were significantly more often methylated than were seminomas (p < 0.001). The three most frequently methylated genes among this subtype were SCGB3A1 (54%), RASSF1A (29%), and HOXA9 (26%). CDH13 and HOXB5 were methylated at low frequencies (10-15%), and EMX2, MSX1, RUNX3, SORBS1, and XPA only rarely (<10%). In conclusion, this study has identified several novel epigenetically deregulated target genes in TGCT development, including homeobox genes and SCGB3A1, suggesting that epigenetic inactivation of key genes in normal development also has an important role in TGCTs.

Clear cell carcinoma of the endometrium: a histopathological and clinical study of 97 cases.

In a histopathologic review of 1985 cases of endometrial carcinoma 97 patients (4.9%) had clear cell carcinoma (CCC). Mean age at diagnosis was 65.3 years. The crude 5- and 10-year survivals for all stages were 42.3 and 30.9%, respectively. Fifty-nine percent of the patients in surgicopathological stage I and 27% in stage II survived 5 years. Myometrial infiltration and vessel invasion were important prognosticators. Ninety percent of the patients with intramucosal tumors survived 5 years, in contrast to only 15% of the patients with deep myometrial infiltration. Seventeen percent of the patients with vessel invasion survived 5 years, in contrast to 49% of the patients without this finding. CCC is one of the most aggressive subtypes of endometrial carcinoma.

Endometrial adenocarcinoma in Norway. A study of a total population.

Fifteen hundred sixty-six patients with adenocarcinoma of the endometrioid type (AC) were studied. These accounted for 78.9% of all 1985 patients with confirmed endometrial carcinoma diagnosed in Norway in the period 1970 through 1978. Four hundred and sixty-nine patients (29.9%) had well-differentiated tumors, 677 (43.2%) were moderately and 420 (26.8%) poorly differentiated. Eighty-one percent of the patients had surgicopathologic Stage I disease, 11% Stage II, 6% Stage III, and 2% Stage IV. Mean age at diagnosis was 62.1 years (range, 36 to 91). The crude 5-year and 10-year survival rates for all patients were 74.1% and 62.2%, respectively. Five-year crude survival was 86.8% for Grade 1 and 58.3% for Grade 3 tumors. The 5-year crude survival for patients with intramucosal tumors was 88.7% as opposed to 46.9% for patients with tumors infiltrating to the serosa. Sixty-six percent of the patients with vessel invasion survived for 5 years in contrast to 88.6% for patients without vessel invasion. Histologic grade, myometrial infiltration, vessel invasion, and lymphocyte reaction surrounding the tumor were strongly interrelated. Multivariate analysis showed that the age of the patient at the time of diagnosis was the most important single prognostic factor. Disregarding age, survival in operated patients was more dependent on the depth of myometrial invasion than on grade and stage of disease.

Serous papillary carcinoma of the endometrium: a histopathological study of 22 cases.

In a histological review of all 1985 cases of endometrial carcinoma in Norway diagnosed in the period 1970 through 1977, 22 patients (1.1%) with serous papillary carcinoma (ESPC) were identified. Mean age at diagnosis was 72 years, which was significantly higher than for patients with ordinary adenocarcinoma. All patients were followed at least 10 years. The crude 5- and 10-year survival rates were 27 and 14%. Only three patients survived longer than 10 years and all of these had had stage I tumors. In 19 available curettage specimens ESPC could be identified in 18. This could have implications regarding choice of therapy because this subtype of endometrial carcinoma is very aggressive. It is most often found in elderly women.