Predicting the rate of adjuvant postoperative chemo/radiation in cervical cancer with tumor size ≥2 cm and <4 cm: An Israeli Gynecologic Oncology Group study.

OBJECTIVE: Women with cervical cancer who undergo radical hysterectomy are often treated postoperatively with chemoradiation. Patient selection that minimizes adjuvant treatment is valuable. We compared two methods for predicting postoperative adjuvant treatment of women with tumor size ≥2 cm and <4 cm. STUDY DESIGN: This multicenter retrospective study included 272 women with tumor size ≥2 cm and <4 cm. A receiver operating characteristic curve (ROC) analysis was used to determine the optimal tumor cutoff size to predict adjuvant treatment. A second analysis compared the rate of adjuvant treatment between women with and without lymph vascular space involvement (LVSI). RESULTS: According to the ROC, the optimal cutoff value of tumor size for predicting adjuvant treatment was 2.95 cm (sensitivity 0.70, specificity 0.67). Tumors were ≥3.0 cm in 166 (61.0%) women. The rate of adjuvant treatment was higher in women with larger tumor diameter (73.8% vs. 47.9%, p < 0.0001). Of the 241 women with a LVSI record, LVSI was present in 81 (34%) women. Among women with LVSI, rates were higher of positive lymph nodes (41.0% vs 14.5%, p < 0.0001) and postoperative adjuvant treatment (83.3% vs. 53.7%, p < 0.001). Among women with tumor size ≥3.0 cm and LVSI, the rate of adjuvant treatment was 90.0%. In the multivariate analysis, both tumor size ≥3.0 cm and the presence of LVSI were independently associated with adjuvant treatment (OR 3.9, 95% CI 2.1-7.1; p < 0.0001 and OR 4.9, 95% CI 2.4-10.0; p < 0.0001, respectively). CONCLUSION: In women with cervical cancer who underwent radical hysterectomy, tumors ≥3 cm were associated with a >70% rate of adjuvant treatment, and LVSI was associated with a >80% rate. These data should be weighed in multidisciplinary consultation with radiation oncologists when deciding treatment strategy.

Does sentinel lymph node biopsy in endometrial cancer surgery have an impact on the rate of adjuvant post operative pelvic radiation? An Israeli Gynecologic Oncology Group Study.

Objective: To compare the rates of post-operative radiotherapy between two methods of lymph nodes assessment during surgical staging for endometrial cancer (EC). Methods: We conducted a comparative study of all consecutive women with endometrial cancer who underwent sentinel lymph node detection and biopsy using blue dye and isotope scan (SLNB) at Kaplan Medical Center and patients from the IGOG database, who underwent staging lymphadenectomy (PLND). The primary outcome was the rate of adjuvant and therapeutic radiation. The secondary outcome was a comparison of disease-free survival (DFS) and overall survival (OS). Results: There were 138 patients in the SLNB group and 1022 women in the PLND group. The detection rate of SLN was 74% for unilateral detection and 54% for bilateral detection. In the PLND group 57% were high risk patients vs. 47% in SLNB group (p = 0.03). 43% of high-risk patients in the PLND group received adjuvant or therapeutic pelvic radiation vs. 28% of high-risk women in the SLNB arm (p = 0.017). No statistically significant difference in recurrence rates nor in death rates had been observed in the high-risk group patients. The 5-years survival in the high-risk PLND group was 80% and the recurrence rate was 19% vs. 75% 5-year survival and 14% recurrence in high-risk SLNB cohort, log-rank p = 0.82 for survival and long-rank p = 0.25 for recurrence. Conclusion: Endometrial cancer patients undergoing lymph node assessment by sentinel lymph node biopsy, receive less pelvic radiotherapy.

Predictors of uncommon location of sentinel nodes in endometrial and cervical cancers.

OBJECTIVE: Sentinel node mapping is widely used in the treatment of gynecologic cancers. The current study aimed to identify predictors of uncommon sentinel lymph node (SLN) locations. METHODS: The current study included women who were operated for endometrial or cervical cancer with attempted sentinel lymph node mapping during surgical staging. Data were collected from electronic charts. The pelvis and the external ilia and obturator basins were common node locations. Para-aortic, pre-sacral, common iliac, internal iliac, and parametrial nodes were considered uncommon locations. We conducted analyses stratified according to common, uncommon, and very uncommon (para-aortic, pre-sacral, parametrial) node location sites. RESULTS: A total of 304 women were enrolled in the current study; 15.8% had SLN in uncommon locations and 4.3% had very uncommon node locations. Body mass index (BMI) was a negative predictor for uncommon SLN locations (OR 0.88, p = 0.03). The use of either indocyanine green (ICG) or Tc99 & blue dye was an independent predictor for uncommon SLN locations (OR 8.24, p = 0.006). More recent surgeries and the presence of positive nodes were independent predictors for very uncommon node locations (OR 2.13, p = 0.011, and OR 9.3, p = 0.002, respectively). CONCLUSIONS: BMI, tracer type, surgical year, and positive nodes were independent predictors for uncommon SLN locations. These findings suggest that surgical effort, technique and experience may result in better identification of uncommon SLN locations.

Minimally invasive approach in endometrial cancer with lower uterine segment involvement in stage ≥ II: A retrospective study.

OBJECTIVE: To compare oncological outcomes in women with lower uterine segment involvement (LUSI) in endometrial carcinoma (EC) stage ≥ II - staged by a minimally invasive surgery (MIS) versus laparotomy. STUDY DESIGN: A retrospective multi-center cohort study. Univariate analysis, Kaplan-Meier survival and Cox proportional hazard analysis were performed to compare between women staged by MIS and those staged by laparotomy. RESULTS: Over a median follow-up period of 3 years (interquartile range, 1.5-6 years) 212 women were included, 68 (32.1%) were surgically staged by MIS. Stages of disease did not vary between MIS and laparotomy and were 32.1%, 51.9%, and 16.0%, in stages II, III and IV - respectively. Adjuvant radiation and chemotherapy rate did not differ between groups. Overall recurrence rate was comparable (p = 0.084). Locoregional recurrence rate was higher in the MIS group odds ratio 2.17, 95% confidence interval 1.19-4.20). Overall and progression free survival were similar in both groups (log rank test p = 0.08 and p = 0.912 respectively). In Cox regression model adjusting for age, comorbidities, tumor grade, stage and adjuvant therapy, route of surgery (MIS vs. laparotomy) was not associated with overall survival (p = 0.169). CONCLUSIONS: In women with advanced EC and LUSI, although MIS is associated with locoregional recurrences, survival is comparable to laparotomy.

Prognostic significance of pretreatment thrombocytosis in endometrial cancer: an Israeli Gynecologic Oncology Group study.

OBJECTIVE: Endometrial cancer prognosis is related to stage, histology, myometrial invasion, and lymphovascular space invasion. Several studies have examined the association between pretreatment thrombocytosis and patient outcomes with contrasting results regarding prognosis. Our aim was to evaluate the association of pretreatment platelet count with outcomes in endometrial cancer patients. METHODS: This is an Israeli Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer, who underwent surgery between January 2002 and December 2014. Patients were grouped as low risk (endometrioid G1-G2 and villoglandular) and high risk (endometrioid G3, uterine serous papillary carcinoma, clear cell carcinoma, and carcinosarcoma). Those with stage I disease were compared with stages II-IV. Disease stages were reviewed and updated to reflect International Federation of Gynecology and Obstetrics (FIGO) 2009 staging. All patients underwent pelvic washings for cytology and total abdominal or laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Pelvic lymph node assessment was performed in patients with tumors of moderate-high risk histology or deep myometrial invasion. Para-aortic sampling was performed at the surgeon's discretion. Patients were categorized by pretreatment platelet count into two groups: ≤400×109/L and >400×109/L (defined as thrombocytosis). Clinical and pathological features were compared using Student t-test, χ2 or Fisher's exact test. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations. RESULTS: Of the 1482 patients included, most had stage I disease (961; 74.8%) and most had endometrioid histology (927; 64.1%). A total of 1392 patients (94%) had pretreatment platelet counts ≤400×109/L and 90 (6%) had pretreatment thrombocytosis. Patients with thrombocytosis had a significantly higher rate of high-grade malignancy, advanced stage, lymphovascular space invasion, low uterine segment involvement, and lymph node metastases. They also had shorter 5 year disease-free survival (65% vs 80%, p=0.003), disease-specific survival (63% vs 83%, p<0.05) and overall survival (59% vs 77%, p<0.05). On multivariate analysis, an elevated pretreatment thrombocyte count remained a significant independent predictor for disease-specific survival and overall survival. CONCLUSIONS: Pretreatment thrombocytosis is an independent prognostic factor for decreased disease-specific survival and overall survival among patients with endometrial cancer, and can serve as a predictor of poor outcome.

The diagnosis of endometrial cancer in women with asymptomatic endometrial polyp does not increase survival rates: an israel gynecologic oncology group study.

OBJECTIVE: To compare outcomes of symptomatic and asymptomatic women with endometrial cancer and a preoperative diagnosis of an endometrial polyp. DESIGN: An Israel Gynecologic Oncology Group multi-center retrospective cohort study. METHODS: Of 635 patients with endometrial cancer and a preoperative diagnosis of an endometrial polyp who underwent surgery between 2002 and 2014 in one of 11 centers in Israel were divided into two groups according to the presence of bleeding symptoms. Outcome measures included recurrence-free survival, disease-specific survival and overall survival. Survival data were plotted according to the method of Kaplan and Meier and compared using the log-rank test. RESULTS: There were 513 symptomatic and 122 asymptomatic women with endometrial cancer and a preoperative diagnosis of an endometrial polyp. The median follow-up was 52 months (range 12-120 months). There were no differences between patients who experienced bleeding and those who did not in 5-year recurrence-free survival (85.2 % vs. 85.7 %; p=0.83, respectively), disease-specific survival (88.2 % vs. 89.2 %; p=0.71, respectively), or overall survival (80.2% vs. 78.4 %; p=0.97, respectively). CONCLUSION: The diagnosis of endometrial cancer in patients with asymptomatic endometrial polyps is not associated with improved outcomes as compared with patients with bleeding. In the absence of factors indicating a high risk of endometrial cancer, clinical and sonographic follow-up is the advised management strategy for these patients.

Age is an independent predictor of outcome in endometrial cancer patients: An Israeli Gynecology Oncology Group cohort study.

INTRODUCTION: Advanced age is considered an adverse factor in endometrial cancers but may be a surrogate for other conditions that impact outcomes. The study objective was to assess the association of age with endometrial cancer features, treatment and prognosis. MATERIAL AND METHODS: In this multicenter cohort study, consecutive women with endometrial cancer treated at 10 Israeli institutions between 2000 and 2014 were accrued in an assimilated database. Postmenopausal women were stratified into age groups with a cut-off of 80. Clinical, pathological and treatment data were compared using t test or Mann-Whitney test for continuous variables, and Chi-square Test or Fisher's Exact test for categorical variables. Main outcome measures included disease recurrence and disease-specific and overall survival; these were plotted using the Kaplan-Meier method and compared using the log-rank test. The association between age and recurrence and survival, adjusted for other clinical and pathological factors, was assessed using multivariable Cox regression modeling. RESULTS: A total of 1764 postmenopausal women with endometrial cancer were identified. Adverse pathological features were more prevalent in older women, including high-risk histologies (35% vs 27%, P = .025), deep myoinvasion (44% vs 29%, P = .001) and lymphovascular involvement (22% vs 15%, P = .024). Surgical staging was performed less frequently among older women (33% vs 56%; P < .001). Chemotherapy was less often prescribed, even for non-endometrioid histologies (72% vs 45%; P < .001). On multivariable analysis, age remained a significant predictor for recurrence (HR = 1.75, P = .007), death of disease (HR = 1.89, P = .003) and death (HR = 2.4, P < .001). CONCLUSIONS: Older age in women with endometrial cancer is associated with more adverse disease features, limited surgery and adjuvant treatment, and worse outcomes. On multivariable analysis, age remains an independent prognosticator in this population.

Increased ultrasonographic endometrial thickness is associated with poor survival in patients with endometrial cancer: An Israel gynecologic oncology group study.

BACKGROUND: We aimed to assess the association of pre-operatively evaluated ultrasonographic endometrial thickness with outcomes of patients with endometrial cancer. METHODS: An Israel Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer who underwent surgery between 2002 and 2014 in one of eleven academic centers. Patients were categorized by endometrial thickness into two groups: ≤20 mm and >20 mm. Clinical and pathological features were compared using Student T-test for continuous variables and Chi-square or Fisher's exact test for categorical variables. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations. RESULTS: 1113 patients in whom endometrial thickness data was recorded were the subject of this study and included 2 groups: ≤20 mm (n = 930), >20 mm (n = 183). The median follow-up was 52 months (range 12-120 months). Patients with endometrial thickness >20 mm had significantly lower recurrence-free survival (log rank, p < .0001), disease-specific survival (log rank, p = .01), and overall survival (log rank, p < .0001). On multivariate Cox proportional hazards analysis, endometrial thickness >20 mm remained independently associated with an increased hazard of recurrence and death (HR = 1.77, 95% CI 1.07-2.96, p = .03 for recurrence; and HR = 1.68; 95% CI 1.07-2.65; p = .03 for overall survival). CONCLUSION: In patients with endometrial cancer, endometrial thickness>20 mm as measured preoperatively by ultrasound, is independently associated with decreased recurrence-free and overall survival. This finding suggests that thick endometrium may be considered as one of the risk factors for poor prognosis.

Is the extent of pelvic lymphadenectomy in the staging of endometrial cancer associated with the yield of metastatic nodes? An Israeli Gynecologic Oncology Group study.

OBJECTIVES: Primary, to explore correlation between the extent of pelvic lymphadenectomy in the surgical staging of endometrial cancer and the number of nodes with metastasis. Secondary, evaluate survival measures in relation to the number of excised nodes. METHODS: A retrospective multi-center study of prospectively collected information of 2014 women with endometrial cancer, 1032 of whom underwent lymph node staging. Spearman's rank correlation was used to assess the correlation between the number of pelvic nodes excised and the number of metastatic nodes. Women's data were dichotomized by the median number of excised pelvic nodes. Kaplan-Meier and log rank tests were used to examine the effect of the number of pelvic nodes excised on survival. RESULTS: There was no significant correlation between the number of pelvic nodes harvested and the number of metastatic lymph nodes (r = 0.301; p = 0.28). The median number of excised pelvic nodes was 9 (range 1-77). There was no difference between women with up to 9 and women with more than 9 lymph nodes excised in the 5-year recurrence-free survival (82.4% vs. 83.9%; p = 0.90), disease-specific survival (83.6% vs. 86.7%; p = 0.37), or overall survival (75.8% vs. 82.8%; p = 0.11). CONCLUSIONS: The extent of pelvic lymphadenectomy in the surgical staging of endometrial cancer is not associated with a higher yield of metastatic nodes or with longer survival. Current focus should be on sentinel node procedures that offer women the benefit of accurate staging without the complications associated with extensive lymphadenectomy.

An Israeli Gynecologic Oncology Group study of statin use and endometrial cancer prognosis.

OBJECTIVE: To assess whether statin use by endometrial cancer patients was associated with a survival advantage. METHODS: A retrospective chart review study, by the Israeli Gynecologic Oncology Group, of consecutive endometrial cancer patients who underwent surgery in one of 11 medical centers between 2002 and 2014. Clinical and pathological reports, and measures of survival were compared between statin users and nonusers. Kaplan-Meier and Cox proportional hazard models were used to assess the effect of using statins on survival measures. RESULTS: Over a mean follow-up period of 6.2 years (range, 1-12 years) for 2017 endometrial cancer patients with complete data, 663 (32.8%) used statins prior to diagnosis and 1354 (67.1%) did not. No statistically significant differences between the groups were observed for most demographic and clinical characteristics. There was no difference between statin users and nonusers in 5-year recurrence-free survival (82% vs 83%; P=0.508), disease-specific survival (86% vs 84%; P=0.549), or overall survival (77% vs 75%; P=0.901). CONCLUSIONS: In this large cohort of patients with endometrial cancer, no significant associations were found between use of statins and endometrial cancer survival.

The oncological safety of hysteroscopy in the diagnosis of early-stage endometrial cancer: An Israel gynecologic oncology group study.

OBJECTIVE: To compare survival measures of women with early-stage endometrial cancer who underwent either hysteroscopy or a non-hysteroscopic procedure as a diagnostic procedure. STUDY DESIGN: An Israel Gynecologic Oncology Group multicenter study of 1324 patients with stage I endometrial cancer who underwent surgery between 2002 and 2014. Patients were divided into two groups: hysteroscopy and non-hysteroscopy (curettage or office endometrial biopsy). Clinical, pathological, and survival measures were compared between the groups. RESULTS: There were 355 patients in the hysteroscopy group and 969 patients in the non-hysteroscopy group. The median follow-up was 52 months (range 12-120 months). There were no differences between the groups in the 5-year recurrence-free survival (90.2% vs. 88.2%; p = 0.53), disease-specific survival (93.4% vs. 91.7%; p = 0.5), and overall survival (86.2% vs. 80.6%; p = 0.22). CONCLUSION: Our findings affirm that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.

Cervical Cancer with Intermediate Risk Factors: Is there a Role for Adjuvant Radiotherapy? A Systematic Review and a Meta-Analysis.

BACKGROUND: The yield of adjuvant radiotherapy in cervical cancer patients with intermediate risk factors is controversial. The objective of our meta-analysis was to shed light on this important issue. MATERIAL AND METHODS: Search was conducted in several databases. By independent screening of titles and abstracts, 2 investigators selected original researches examining the effect of adjuvant radiation treatment on overall survival and progression-free survival in cervical cancer patients with intermediate risk factors. RESULTS: Of the 5 articles included, a total of 591 patients with intermediate risk factors were encompassed. Statistical significance was noted in favor of radiation therapy in a subgroup of patients with 2 or more intermediate factors in terms of recurrence (OR 0.46 [95% CI 0.28-0.74, p = 0.001]) and overall survival (OR 1.86 [95% CI 1.03-3.36, p = 0.04]). After adding patients with one risk factor, radiation exerted a non-significant effect on recurrence rate, overall survival, disease-free survival, and 5-year cancer-specific survival, while increasing the rate of gastrointestinal side effects (2.4 vs. 0%, p = 0.0156). CONCLUSIONS: Adjuvant radiation therapy decreases the risk for recurrence and increases the overall survival in patients with 2 intermediate risk factors. These benefits were not shown after adding patients with one risk factor.

Endometrial Polyp Size and the Risk of Malignancy in Asymptomatic Postmenopausal Women.

OBJECTIVE: The appropriate management of endometrial polyps in asymptomatic postmenopausal patients remains controversial. The aim of the study was to evaluate the relationship between endometrial polyp size and malignancy risk among asymptomatic postmenopausal women. METHODS: This observational retrospective study investigated 472 postmenopausal asymptomatic women who underwent hysteroscopic polypectomy between 2010 and 2014 (Canadian Task Force Classification II-3). RESULTS: Of the 472 women, premalignant and malignant lesions were found in 11 (2.33%) cases; four (0.84%) had endometrial carcinoma, and seven (1.49%) had atypical endometrial hyperplasia. The incidence of premalignant or malignant lesions among various cut-offs of polyp size (10, 15, 20 mm) was not significantly different. CONCLUSION: In the current series no significant risk factor for malignancy was found among different cut-offs of polyp size.

Effect of Menopausal Status on the Diagnosis of Endometrial Polyp.

OBJECTIVE: This study sought to compare the value of transvaginal ultrasonography (TVUS) and hysteroscopy in premenopausal and postmenopausal women in the diagnosis of endometrial polyp. METHODS: The records of 694 women with an ultrasonographic diagnosis of suspected endometrial polyp who underwent hysteroscopy were studied. Patients were divided into two groups according to menopausal status, and a comparison was made between two groups. RESULTS: There were 299 postmenopausal and 395 premenopausal women in the study. Hysteroscopy confirmed the ultrasonographic diagnosis of endometrial polyp in 212 (71%) and 212 (53%) patients in the postmenopausal and premenopausal groups, respectively (P = 0.001). In postmenopausal patients, 94% of the polyps observed by hysteroscopy were confirmed by histology, whereas in premenopausal patients, the percentage was 85% (P = 0.004). CONCLUSION: In premenopausal patients, the diagnostic value of TVUS and hysteroscopy is lower than in postmenopausal patients. The appropriate time for TVUS and hysteroscopy should be scheduled in premenopausal women, especially in women with abnormal uterine bleeding.

Is there a survival advantage in diagnosing endometrial cancer in asymptomatic postmenopausal patients? An Israeli Gynecology Oncology Group study.

BACKGROUND: Incidental ultrasonographic findings in asymptomatic postmenopausal women, such as thickened endometrium or polyps, often lead to invasive procedures and to the occasional diagnosis of endometrial cancer. Data supporting a survival advantage of endometrial cancer diagnosed prior to the onset of postmenopausal bleeding are lacking. OBJECTIVE: To compare the survival of asymptomatic and bleeding postmenopausal patients diagnosed with endometrial cancer. STUDY DESIGN: This was an Israeli Gynecology Oncology Group retrospective multicenter study of 1607 postmenopausal patients with endometrial cancer: 233 asymptomatic patients and 1374 presenting with postmenopausal bleeding. Clinical, pathological, and survival measures were compared. RESULTS: There was no significant difference between the asymptomatic and the postmenopausal bleeding groups in the proportion of patients in stage II-IV (23.5% vs 23.8%; P = .9) or in high-grade histology (41.0% vs 38.4%; P = .12). Among patients with stage-I tumors, asymptomatic patients had a greater proportion than postmenopausal bleeding patients of stage IA (82.1% vs 66.2%; P < .01) and a smaller proportion received adjuvant postoperative radiotherapy (30.5% vs 40.6%; P = .02). There was no difference between asymptomatic and postmenopausal bleeding patients in the 5-year recurrence-free survival (79.1% vs 79.4%; P = .85), disease-specific survival (83.2% vs 82.2%; P = .57), or overall survival (79.7% vs 76.8%; P = .37). CONCLUSION: Endometrial cancer diagnosed in asymptomatic postmenopausal women is not associated with higher survival rates. Operative hysteroscopy/curettage procedures in asymptomatic patients with ultrasonographically diagnosed endometrial polyps or thick endometrium are rarely indicated. It is reasonable to reserve these procedures for patients whose ultrasonographic findings demonstrate significant change over time.

[SENTINEL LYMPH NODES DISSECTION IN GYNECOLOGICAL MALIGNANCIES].

INTRODUCTION: During the last decade sentinel lymph nodes biopsy has become an essential part of primary surgical treatment in a number of malignancies including breast cancer, melanoma and head-and-neck malignancies. Dye or radioactive substances are injected at the primary tumor site, followed by pre-operative and intra-operative mapping. During surgery only positive lymph nodes are being dissected instead of a complete dissection of the lymphatic basin. The advantages of sentinel lymph nodes dissection are reducing the side effects of extensive lymph nodes dissection, while maintaining high detection rates and sensitivity in identifying cases with lymphatic tumor spread. In the past years, the use of sentinel lymph nodes biopsy has also been incorporated in the treatment of gynecological malignancies. In vulvar cancer, it has been shown that sentinel lymph nodes biopsy is correlated with the same survival and recurrence rates as full groin lymph nodes dissection, while substantially lowering complications and especially morbid lymphedema. Preliminary experience in cervical cancer and carcinoma of the endometrium also displays the feasibility and liability of this method. Yet, there are still several controversies regarding the optimal detection method, site of injection and its oncological safety. In this article we present a review of the current literature on this evolving field.

Can malignant potential of endometrial polyps be determined by incorporating the endometrial intraepithelial neoplasia (EIN) classification?

OBJECTIVE: The reported frequency of malignant or premalignant changes confined to endometrial polyps (EP) is 0.5-6%. The management of atypical endometrial hyperplasia (AEH) confined to EP is not yet established. Recently, an alternative pathological nomenclature has emerged using the term endometrial intraepithelial neoplasia (EIN) instead of atypia. The objective of this study was to evaluate the safety of conservative hysteroscopic resection of endometrial polyps with AEH or EIN. METHODS: Retrospective cohort study of all cases of hysteroscopic resections of EP was performed at a single center between the years 2000-2011. All patients with a pathologic diagnosis of AEH in EP were included. A post-hoc revision of the pathologic specimens was made according to the EIN classification. RESULTS: Of the 32 patients with AEH in EP, 25 had normal endometrial curetting. Even with AEH confined to EP, 12 cases (48%) showed AEH (11 cases) or carcinoma (1 case) in the hysterectomy specimens. EIN in EP (14 cases) was correlated with 57% of diagnosis of EIN or carcinoma in the uterus; whereas in the absence of EIN in EP only 1 of 9 cases showed EIN in the final pathologic specimen (p=0.002), and none with carcinoma, which yields a PPV of 14% and a NPV of 100%. CONCLUSION: The diagnosis of EIN in EP may be a better predictor than AEH for endometrial involvement with malignant or pre-malignant neoplasms. The safety of conservative hysteroscopic resection of EP with AEH/EIN is questioned.

L1CAM is expressed in triple-negative breast cancers and is inversely correlated with androgen receptor.

BACKGROUND: Breast cancer is a heterogeneous disease displaying distinct molecular features and clinical outcome. The molecular profile of triple-negative breast cancers (TNBCs) overlaps with that of basal-like breast cancers that in turn show similarities with high-grade serous ovarian and endometrial carcinoma. L1CAM is an established biomarker for the latter cancers and we showed before that approximately 18% of primary breast cancers are positive for L1CAM and have a bad prognosis. Here we analysed the expression of L1CAM breast cancer subtypes. METHODS: We analyzed mRNA and protein expression data from different breast cancer cohorts for L1CAM, estrogen receptor, progesterone receptor, Her-2 and Androgen receptor (AR) and correlated the data. We performed Western blot analysis on tumor cell lysates and carried out chromatin-immuno-precipitation (CHIP) after AR overexpression. RESULTS: We find that L1CAM is expressed preferentially though not exclusively in TNBCs. Using the human cancer genome atlas database and two independent breast cancer cohorts we find that L1CAM is inversely correlated with androgen receptor (AR) expression. We found that L1CAM(high)AR(low) primary breast tumors have the worst clinical outcome. Overexpression of AR in MDA-MB436 breast cancer cells decreased L1CAM expression at the protein and mRNA level and CHIP-analysis revealed binding of AR to the L1CAM promoter region. CONCLUSIONS: These results suggest that L1CAM in breast cancer is under AR control. The data also strongly advocate the use of L1CAM assessment in breast cancer diagnosis. We suggest that L1CAM expression could be causally related to the bad prognosis of TNBCs.

The omentum and omentectomy in epithelial ovarian cancer: a reappraisal. Part I--Omental function and history of omentectomy.

OBJECTIVE: This article reviews the literature concerning the function of the omentum and how omentectomy came to be part of the staging and treatment of epithelial ovarian cancer. METHODS: A review of the English language literature based on a MEDLINE (PubMed) database search using the key words: ovary, cancer, carcinoma, omentum, and omentectomy. An additional collection of reports was found by systematically reviewing all references from retrieved papers. RESULTS: Descriptions of the omentum can be found as far back as the time of the ancient Egyptians. An immunologic role of the omentum was confirmed in 1980s when "milky spots" were described. Omentectomy arrived as part of the ovarian cancer guidelines in the 1960s after observing that the omentum was a frequent site of metastasis and that patients with removal of all diseased tissue did better. The exact role of the omentum in immunology and cancer remains incompletely understood. CONCLUSIONS: Historically, occult omental metastases in otherwise early disease have led to the inclusion of omentectomy for the purpose of accurate staging and for a possible therapeutic benefit. Laboratory studies on the role in cancer of the omental fat and milky spots are controversial.

L1CAM in early-stage type I endometrial cancer: results of a large multicenter evaluation.

BACKGROUND: Despite the excellent prognosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to predict clinical outcome. METHODS: We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The Kaplan-Meier method and Cox proportional hazard model were applied for survival and multivariable analyses. A machine-learning approach was used to validate variables for predicting recurrence and death. RESULTS: Of 1021 included cancers, 17.7% were rated L1CAM-positive. Of these L1CAM-positive cancers, 51.4% recurred during follow-up compared with 2.9% L1CAM-negative cancers. Patients bearing L1CAM-positive cancers had poorer disease-free and overall survival (two-sided Log-rank P < .001). Multivariable analyses revealed an increase in the likelihood of recurrence (hazard ratio [HR] = 16.33; 95% confidence interval [CI] = 10.55 to 25.28) and death (HR = 15.01; 95% CI = 9.28 to 24.26). In the L1CAM-negative cancers FIGO stage I subdivision, grading and risk assessment were irrelevant for predicting disease-free and overall survival. The prognostic relevance of these parameters was related strictly to L1CAM positivity. A classification and regression decision tree (CRT)identified L1CAM as the best variable for predicting recurrence (sensitivity = 0.74; specificity = 0.91) and death (sensitivity = 0.77; specificity = 0.89). CONCLUSIONS: To our knowledge, L1CAM has been shown to be the best-ever published prognostic factor in FIGO stage I, type I endometrial cancers and shows clear superiority over the standardly used multifactor risk score. L1CAM expression in type I cancers indicates the need for adjuvant treatment. This adhesion molecule might serve as a treatment target for the fully humanized anti-L1CAM antibody currently under development for clinical use.