Pretreatment assessment of prognostic indicators in endometrial cancer

OBJECTIVE: The object of this study was to assess the association of histologic, cytokinetic, and molecular variables in preoperative endometrial samples with extrauterine disease, recurrence, and survival among patients with endometrial cancer. STUDY DESIGN: In a case-cohort study of 125 women, ploidy, S-phase fraction, proliferative index, deoxyribonucleic acid index, proliferating cell nuclear antigen, MIB-1 proliferation marker, p53 tumor suppressor gene, and cytoplasmic HER-2/neu oncogene and bcl-2 expressions were quantitated. RESULTS: A model with only one independent term predicted progression-free survival; that variable was p53 (P <. 0001; relative risk, 5.60). A model with two independent terms predicted disease-related survival; these variables were p53 (P =. 0002; relative risk, 7.39) and MIB-1 (P =.03; relative risk, 3.27). Among patients with tumors with both p53 and MIB-1 expression exceeding 33%, a total of 32% had died of disease by 2 years. A model for predicting extrauterine disease selected two independent variables: p53 (odds ratio, 3.20; P =.01) and ploidy (odds ratio, 2. 16; P =.04). An advanced surgical stage was encountered in 26% to 35% of cases in which either the p53 expression exceeded 33% or the deoxyribonucleic acid content was nondiploid and in 53% of cases in which both variables were unfavorable. CONCLUSIONS: Preoperative evaluation of quantifiable cytokinetic and molecular variables can assist in identifying tumor types that are predisposed toward a more aggressive clinical course.     

The diagnostic and prognostic value of serum YKL-40 in endometrial cancer

Purpose

To evaluate the diagnostic and prognostic value of serum YKL-40 in endometrial cancer (EC).

Methods

Serum YKL-40 levels were detected and compared in 34 of the 50 cases with EC before surgery, in 22 of the 34 with EC after surgery, in 30 cases with uterine myoma, and in 30 healthy women as normal controls. Receiver operating characteristics (ROC) curves were adopted for diagnosis and calculation of area under each ROC curve in EC. The progression-free survival (PFS) and overall survival (OS) between YKL-40 positive and negative patients were compared in the follow-up.

Results

The mean pre-operative serum YKL-40 values were significantly higher than that in the uterine myoma cases and in the healthy women (P = 0.000). The mean post-operative serum YKL-40 in the 22 EC cases was significantly lower than pre-operative serum YKL-40 levels in these cases (P = 0.000). There were critical differences between the area under ROC curve for YKL-40 and CA125 (P = 0.053). The PFS and OS for the YKL-40-positive patients were significantly shorter than those for the YKL-40-negative patients.

Conclusion

Preliminary investigations have shown that serum YKL-40 level may have a definite clinical value in the diagnosis and prognosis of EC.     

Assessment of prognostic factors in stage IIIA endometrial cancer

OBJECTIVE: The objective of this study was the assessment of prognostic factors in stage IIIA endometrial cancer. METHODS: Between 1984 and 1993, 51 patients with stage IIIA endometrial cancer received definitive treatment at our institution. Thirty-seven patients had positive peritoneal cytologic findings only (stage IIIA1), and 14 had adnexal or uterine serosal involvement (USI) (stage IIIA2). Median follow-up of surviving patients was 82.5 months. RESULTS: The 5-year disease-related survival (DRS) and recurrence-free survival (RFS) were 88 and 73%, respectively. RFS was 79% in patients with stage IIIA1 disease, compared with 57% in patients with stage IIIA2 disease (P = 0.04). However, DRS did not significantly differ between stages IIIA1 and IIIA2. In the 37 patients with stage IIIA1 tumors, histologic grade 3, nonendometrioid histologic subtype, and lymphovascular invasion (LVI) significantly predicted a poor prognosis, with extraabdominal sites of failure (P < 0.05). Of the 22 patients who had stage IIIA1 disease with endometrioid histologic subtype and without LVI, none had recurrence [17 had whole abdominal irradiation (WAR) or intraperitoneal injection of (32)P, 2 had pelvic external radiotherapy (PRT)]. By contrast, of the 15 patients with either nonendometrioid histologic subtype or LVI, 9 (60%) had recurrence and 7 (47%) died of disease (12 had WAR or (32)P). An extraabdominal component was present in 7 of the 9 recurrences observed in this subgroup. Among the 14 patients with stage IIIA2 tumors (6 had WAR, 6 had PRT), those with USI had a 5-year DRS of 83% and a rate of extraabdominal failure of 83%, compared with 100 and 12.5% in patients without USI (P < 0.05). CONCLUSION: Patients with stage IIIA endometrial cancer who have endometrioid tumors, no LVI, and positive peritoneal cytologic findings as the only sign of extrauterine disease have an excellent prognosis. Nonendometrioid histologic subtype, LVI, and USI are strong predictors of distant failures and poor prognosis. Patients with either of these histologic factors should be considered candidates for systemic adjuvant therapy.     

The accuracy of magnetic resonance imaging for preoperative deep myometrium assessment in endometrial cancer

ObjectiveTo evaluate the accuracy of preoperative magnetic resonance imaging (MRI) to detect deep myometrial invasion in patients with endometrial cancer.Materials and MethodsWe retrospectively reviewed 66 cases of women with endometrial cancer, who underwent preoperative MRI assessment and surgical staging between January 2006 and October 2010. The MRI findings were then compared with the pathology results. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI in detecting deep myometrium invasion were evaluated.ResultsThe sensitivity, specificity, accuracy, PPV, and NPV results of MRI for the detection of deep myometrium invasion were 92.52%, 74.35%, 81.81%,71.42%, and 93.54%, respectively, with a kappa of 0.64. In the postmenopausal group, the values were 100%, 55.5%, 74.19%, 61.9%, and 100%. In the premenopausal women, they improved to 85.7%, 90.47%, 88.57%, 88.71%, and 90.47%. The sensitivity (100%) was better than the specificity (55.56%) in the postmenopausal women. The predictive value was markedly higher in the premenopausal women than the postmenopausal women (85.7% vs. 61.9%).ConclusionIn patients with endometrial cancer, a preoperative MRI contributes to accurate staging, allowing planning for the scale of surgery and preoperative counseling. In our study, the pretreatment identification of myometrium invasion provided the opportunity for small-scale surgery in the premenopausal women with early endometrial cancer. However, for the postmenopausal patients, the standard surgical procedure is indicated even if the degree of myometrium invasion is low.     

The prognostic value of quantitative analysis in the endometrial carcinoma

The epithelial and stromal components in 146 adenocarcinomas, adenocanthomas and adenosquamous carcinomas of the endometrium were quantified morphometrically on Feulgen-stained tissue sections. The classification of the tumors was based on the criteria of World Health Organization and International Federation of Gynecology and Obstetrics. As expected, the survival percentage of the patients fell with the advancing clinical stage and histological grade. The ratio of the epithelial cells to the stromal ones proved to be a good prognostic indicator and may be useful in identification of cases with the most favorable prognosis among grade 1 tumors. A high mitotic activity predicted poor prognosis to the patient although statistical significance was not achieved.     

Depth of myometrial invasion in endometrial cancer: Preoperative assessment by transvaginal ultrasonography

Twenty-five patients with cancer of the uterus underwent transvaginal sonography (TVS) to assess depth of myometrial invasion. All scans were performed with a 5.0-MHz curvilinear array probe (Toshiba, Inc., Tustin, CA) within 1 week of hysterectomy. In 21 cases (84%) sonography correctly predicted the depth of invasion (within 15% of actual). Only one of three cases with cervical involvement was detected. Transvaginal sonography can accurately detect depth of myometrial invasion and is well suited as a screening test to detect high-risk patients for consultation or referral.     

The value of preoperative platelet count in the prediction of cervical involvement and poor prognostic variables in patients with endometrial carcinoma

OBJECTIVE(S): To evaluate the relationship between preoperative platelet counts and prognostic factors extensively, among endometrial cancer patients, especially with respect to cervical involvement. METHODS: One-hundred fifty-five patients with endometrial carcinoma, who underwent surgery as the initial treatment consisting peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, systematic pelvic-paraaortic lymphadenectomy, and omentectomy were retrospectively analyzed. RESULTS: There were no differences with respect to age, histological type (endometrioid vs. non-endometrioid), depth of myometrial invasion, peritoneal cytology, LVSI, and lymphatic metastasis. However, advanced stage (stages III and IV), poorly differentiated tumor grade (grade 3), the presence of cervical and adnexal involvements were associated with significantly higher median preoperative platelet counts. Accepting 325.000/microl platelet count as a threshold value, multivariate analysis revealed cervical involvement (P=0.008; OR=1.84, 95% CI:1.17-2.89) and presence of high grade histology (P=0.014; OR=2.23, 95% CI:1.18-4.23, for grade 3 disease) to be significantly associated with higher platelet count. At a cut-off value of 326.000/microl, 42.3% sensitivity and 82.8% specificity for the prediction of cervical involvement was observed under receiver operator characteristic curve method. CONCLUSION(S): Higher preoperative platelet counts, even in conditions with normal range (150.000-400.000/microl), may reflect poor prognostic factors such as cervical involvement and high grade among patients with endometrial carcinoma. Also, the higher platelet count should be taken into consideration for the necessity of radical hysterectomy.     

The value of transvaginal ultrasonography in the prediction of endometrial pathologies in asymptomatic postmenopausal breast cancer tamoxifen-treated patients

OBJECTIVE: There is no established ultrasonographic endometrial cutoff value for the diagnosis of endometrial pathologies in asymptomatic postmenopausal tamoxifen (TAM)-treated patients. We attempted to seek the most accurate cutoff value. MATERIALS AND METHODS: Multiple ultrasonographic cutoff points were evaluated by logistic regression analysis based on 279 patients who had transvaginal ultrasonographic examinations followed by endometrial histopathological analysis. Performance characteristics were calculated with correlation to the endometrial histological findings. We also calculated how many endometrial pathologies could have been left undiagnosed and the number of endometrial samplings, with different cutoff values, which could have been avoided. RESULTS: There was a gradual increase in specificity and a gradual decrease in sensitivity of the ultrasonographic studies with the increase of endometrial thickness. More overall and more various endometrial pathologies were identified with the increase in cutoff values. The best cutoff value appeared to be 15 mm (sensitivity 37.9%, specificity 87.2%, positive predictive value 63.0%, and negative predictive value 70.2%). However, by avoiding performance endometrial sampling up to this cutoff value, 62.2% endometrial pathologies including 48 endometrial polyps, one case of endometrial hyperplasia with atypia, and one case of endometrial cancer may have been left undiagnosed. At the same time, endometrial sampling in 78.5% of cases may have been avoided. CONCLUSION: In asymptomatic postmenopausal breast cancer tamoxifen-treated patients, the use of wider ultrasonographic endometrial cutoff values could be associated not only with the performance of fewer endometrial samplings, but also with a higher possibility of endometrial pathologies, including endometrial cancers, being left undiagnosed.     

Combined use of preoperative transvaginal ultrasonography and intraoperative gross examination in the assessment of myometrial invasion in endometrial carcinoma

Objective

To evaluate the diagnostic performance of gross examination and transvaginal ultrasonography in the assessment of the depth of myometrial infiltration when they are used alone or together as a combined test.

Study design

The data of 219 consecutive patients with a diagnosis of endometrial cancer were evaluated retrospectively. Transvaginal ultrasound was carried out as a part of the routine preoperative work-up within three days of surgical intervention in all cases. All patients underwent hysterectomy with bilateral salpingo-oophorectomy and routine surgical staging and all uterine specimens were examined immediately after hysterectomy. The depth of myometrial invasion was classified into two groups: no or <50% invasion and ≥50% invasion. The findings of ultrasound and intraoperative gross examination were compared with the final histopathological results. The data of these two methods were integrated to evaluate the diagnostic performance of the combined test. If the results of myometrial invasion evaluation were different for the same patient, the deeper one (the depth of invasion ≥50%) was accepted.

Results

Sensitivity, specificity, PPV, NPV and accuracy of preoperative ultrasonography in predicting myometrial infiltration ≥50% were 62%, 81%, 60%, 82%, and 75% respectively. The corresponding rates for intraoperative gross examination were 61%, 88%, 70%, 83% and 79%, respectively. For the combined test they were 78%, 76%, 60%, 88% and 70% respectively. There was no statistically significant difference in sensitivity and specificity between ultrasound and gross examination. The sensitivity of the combined test was significantly higher than that of ultrasound and gross examination (p = 0.001 and p < 0.0001, respectively). The specificity of the combined test was significantly lower than that of TVS and gross examination (p = 0.008 and p < 0.0001, respectively).

Conclusion

Combining ultrasonography and intraoperative gross examination may be a good option to assess the depth of myometrial invasion, as it has a higher sensitivity and negative predictive value in comparison to using these methods alone.     

The prognostic significance of positive peritoneal cytology in endometrial cancer

A retrospective analysis of clinical data extracted from hospital records of 145 patients who had had primary surgical treatment for endometrial cancer in Queen Mary Hospital, Hong Kong, from 1987 to 1993 was performed to study the prognostic significance of positive peritoneal cytology. Positive peritoneal cytology was found to be associated with poor prognostic factors such as deep myometrial invasion, high grade tumor, extrauterine spread and lymphovascular permeation. By univariate analysis, all the poor prognostic factors were found to be significant in affecting survival. These included age above 65, nonadenocarcinoma histology, deep myometrial invasion, positive cytology, extrauterine involvement and lymphovascular involvement. By multivariate analysis, only histology and extrauterine involvement remained significant. In patients with positive cytology, 61.1% had extrauterine involvement at initial presentation. Patients who had positive cytology and extrauterine disease had the shortest survival. The survival was independent of cytology result when the tumor was confined to the uterus.     

The prognostic value of fetal ultrasonography before induction of labour.

OBJECTIVE: To investigate whether ultrasound examination of the fetus and amniotic fluid before induction of labour can provide useful prognostic information about the course of labour and mode of delivery. DESIGN: A prospective observational study. SETTING: The delivery suite of St Mary's Hospital, London. SUBJECTS: 101 women undergoing induction of labour. MEASURED VARIABLES: Biparietal diameter, head circumference, abdominal circumference, occipital position, amniotic fluid volume and umbilical artery Doppler velocimetry waveforms. MAIN OUTCOME MEASURES: The outcome of labour was assessed in terms of the induction delivery interval, the mode of delivery and the incidence of abnormal cardiotocograms in labour. RESULTS: Seven women were delivered by emergency caesarean section early in the first stage of labour because of a significant abnormality of the fetal heart trace and these pregnancies were characterized by small fetal abdominal circumference measurements. Marked oligohydramnios was also noted in five of these seven subjects. Small or average size babies who were surrounded by an adequate volume of amniotic fluid tended to be born spontaneously, whereas the majority of operative deliveries for failure to progress in labour were associated with fetal abdominal circumference measurements > or = 340 mm. The mean Bishop score of women before labour who delivered spontaneously was not significantly different from the scores of women who had a forceps delivery or caesarean section. Abnormal cord Doppler waveforms were observed in only one instance. CONCLUSIONS: In women undergoing induction of labour, the measurement by ultrasonography of two variables (fetal abdominal circumference and amniotic fluid volume) may allow the prospective identification of pregnancies at increased risk of fetal distress or dystocia. If these findings can be replicated in early spontaneous labour than more rational utilization of resources may be possible in hospital based obstetric practice.     

Preoperative assessment of myometrial invasion and cervical involvement of endometrial cancer by transvaginal ultrasonography

The aim of the study was to assess the depth of myometrial invasion and cervical involvement by endometrial cancer using preoperative 6.5-MHz, high-frequency transvaginal ultrasonography as compared with postoperative assessment using histopathological examination. The study included 47 patients with histologically proven cancers of the endometrium. All patients underwent transvaginal sonography before surgery. The depth of myometrial invasion was classified as none, inner half of the uterine wall, and outer half of the uterine wall. Cervical spread is recorded as positive or negative. Of 36 (76.6%) patients with proven myometrial invasion, 33 cases (91.66%) were revealed by sonography. Histologically proven cervical invasion that correlated with sonography was shown in 3 patients (75%). In 7 patients (14.9%) ultrasonography could not correctly predict the depth of myometrial invasion. The depth of invasion was underestimated in 4 (8.5%) cases and overestimated in 3 (6.4%) cases. Preoperative assessment of invasion of the uterine wall and cervical spread by transvaginal ultrasonography had an accuracy of 85 and 97.8% if correlated with the definitive histopathological examination. The role of transvaginal ultrasonography in preoperative assessment of the depth of myometrial invasion and cervical involvement in patients with endometrial cancer needs to be studied further before making reliable conclusions.     

Elevated platelet count in patients with endometrial carcinoma: correlation with selected prognostic factors and with survival

Platelets may play a role in the metastatic process and, among gynecologic malignancies, thrombocytosis has been reported in cervical and ovarian malignancy. The present study was conducted in order to assess the prevalence of thrombocytosis in endometrial carcinoma and to correlate platelet count with prognostic factors and with survival. The prevalence of preoperative thrombocytosis was assessed in 66 endometrial carcinoma patients and their platelet count was correlated with selected prognostic factors and with projected survival. The prevalence of thrombocytosis ( 400 000 µL⁻¹) was low (one of 66 patients) compared with that in cervical and ovarian carcinoma. Nevertheless, a significant ( P = 0.032) correlation was found between an elevated ( 300 000 µL⁻¹) platelet count and unfavorable grade of differentiation. Patients with an elevated count also had a poorer survival rate and a higher prevalence of older age, high stage and deep myometrial invasion, but this trend did not reach statistical significance. The combination of unfavorable grade and an elevated platelet count had a higher specificity and positive predictive value for deep myometrial invasion than unfavorable grade alone. The prevalence of thrombocytosis in endometrial carcinoma is low. An elevated platelet count may have some prognostic significance, but its ultimate role in endometrial carcinoma remains to be elucidated.     

Histomorphologic prognostic factors in stage I endometrial cancers

The prognostic significance of qualitative and quantitative morphological tumour characteristics for endometrial carcinoma of stage I (FIGO) is to be ascertained from the available 230 operation specimens from 1976 to 1983 (inclusive). The fundamental objective is to design a standardized and reliably reproducible histological technique. By utilizing a multi-dimensional statistical comparison (multiple regression analysis), the maximal relative extent of the endometrial invasion as a determinant prognostic feature shall also be ascertained. Furthermore, the degree of differentiation (Grading) and tumour type (Typing) influence the survival rate whereas the maximal superficial extension of the carcinoma has no significant prognostic importance.