Epithelial Ovarian Cancer and the Occurrence of Skin Cancer in The Netherlands: Histological Type Connotations

Background. Patients with epithelial ovarian cancer have a high risk of (non-)melanoma skin cancer. The association between histological variants of primary ovarian cancer and skin cancer is poorly documented. Objectives. To further evaluate the risk of skin cancer based on the histology of the epithelial ovarian cancer. Methods. A cross-sectional study within a large population-based dataset. Results. Skin cancer was found in 2.7% (95% CI: 2.3–3.1) of the 5366 individuals forming our dataset. The odds ratio (OR) for endometrioid cancer in the ovary to skin cancer in the under 50 age group was 8.9 (95% CI: 3.2–25.0). The OR decreased in older patients to 1.2. Conclusions. Patients with epithelial ovarian malignancies show an increased risk of skin cancer. A significantly increased risk (4.3%) for endometrioid ovarian cancer was found in the group aged under 50

The Association between Primary Endometrioid Carcinoma of the Ovary and Synchronous Malignancy of the Endometrium

Objective. Ovarian and endometrial cancers coincide rather frequently in the same patient. Few data are available on the involvement of the specific morphological subtypes. To identify histological pathways in the synchronous occurrence, a population-based study was performed in The Netherlands. Methods. Using the national pathology database (PALGA) information of ovarian cancers and of earlier or later cancer in the endometrium was obtained. 5366 Patients were identified with primary malignant epithelial or borderline malignancy. Results. In 157 cases (2.9%) a new primary malignancy in the endometrium was diagnosed (146 within 1 year). The ratio of observed versus expected number of synchronous malignancy in the endometrium was estimated at 3.6 (95% CI: 2.7–4.7). Among 460 ovarian endometrioid carcinoma patients 53 cases showed a second primary endometrial cancer; 40 out of these 53 cases (75.5%) showed at both organ sites an endometrioid adenocarcinoma. Conclusion. These findings suggest an important role for the endometrioid subtype and prompt to mechanism-based studies incorporating molecular techniques

Epithelial Ovarian Carcinoma Types and the Coexistence of Ovarian Tumor Conditions

Objective. Ovarian carcinomas are presumed to arise within ovarian inclusion cysts or from a coexisting epithelial lesion in the ovary. Insight may be gained by relating different subtypes of ovarian cancer with the presence of coexisting tumor-like conditions. Methods. The Dutch nation-wide pathology database PALGA (Pathologisch Anatomisch Landelijk Geautomatiseerd Archief) identified the various histopathological subtypes of ovarian cancer in 824 patients diagnosed in 1996–2003, and recorded the presence of epithelial tumor conditions around the ovarian tumors. In addition, a PALGA database of all 153 consecutive patients referred to the Nijmegen University Medical Centre in 2007 for histopathological work-up was analyzed. Results. The prevalence of coexisting ovarian tumor conditions was 16.4% (135 out of 824 patients, (95% CI: 8.4%–24.4%)). The coexistence was highest for endometrioid, mucinous, clear cell, and borderline malignancies. The referral group revealed 35% (54 out of 153 patients, (95% CI: 28%–42%)) of coexisting epithelial ovarian tumor conditions. Conclusion. One in six patients with a malignant ovarian tumor has a coexisting epithelial tumor condition in the ovary, which is also rather frequently observed in the diagnostic work-up practice

Relevance of Molecular Profiling in Patients With Low-Grade Endometrial Cancer

Molecular Profiling; Endometrial CancerPerfil molecular; Càncer d'endometriPerfil molecular; Cáncer de endometrioImportance Patients with low-grade (ie, grade 1-2) endometrial cancer (EC) are characterized by their favorable prognosis compared with patients with high-grade (ie, grade 3) EC. With the implementation of molecular profiling, the prognostic relevance of tumor grading might lose attention. As most patients present with low-grade EC and have an excellent outcome, the value of molecular profiling for these patients is unclear. Objective To determine the association of molecular profiling with outcomes among patients with low-grade EC. Design, Setting, and Participants This retrospective cohort study included a multicenter international European cohort of patients diagnosed with EC between 1994 and 2018, with a median follow-up of 5.9 years. Molecular subgroups were determined by next-generation sequencing using single-molecule molecular inversion probes and by immunohistochemistry. Subsequently, tumors were classified as polymerase epsilon (POLE)-altered, microsatellite instable (MSI), tumor protein p53 (TP53)-altered, or no specific molecular profile (NSMP). Patients diagnosed with any histological subtypes and FIGO (International Federation of Gynecology and Obstetrics) stages of EC were included, but patients with early-stage EC (FIGO I-II) were only included if they had known lymph node status. Data were analyzed February 20 to June 16, 2022. Exposures Molecular testing of the 4 molecular subgroups. Main Outcomes and Measures The main outcome was disease-specific survival (DSS) within the molecular subgroups. Results A total of 393 patients with EC were included, with a median (range) age of 64.0 (31.0-86.0) years and median (range) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 29.1 (18.0-58.3). Most patients presented with early-stage (290 patients [73.8%]) and low-grade (209 patients [53.2%]) disease. Of all patients, 33 (8.4%) had POLE-altered EC, 78 (19.8%) had MSI EC, 72 (18.3%) had TP53-altered EC, and 210 (53.4%) had NSMP EC. Across all molecular subgroups, patients with low-grade EC had superior 5-year DSS compared with those with high-grade EC, varying between 90% to 100% vs 41% to 90% (P < .001). Multivariable analysis in the entire cohort including age, tumor grade, FIGO stage, lymphovascular space invasion, and the molecular subgroups as covariates found that only high-grade (hazard ratio [HR], 4.29; 95% CI, 2.15-8.53; P < .001), TP53-altered (HR, 1.76; 95% CI, 1.04-2.95; P = .03), and FIGO stage III or IV (HR, 4.26; 95% CI, 2.50-7.26; P < .001) disease were independently associated with reduced DSS. Conclusions and Relevance This cohort study found that patients with low-grade EC had an excellent prognosis independent of molecular subgroup. These findings do not support routine molecular profiling in patients with low-grade EC, and they demonstrate the importance of primary diagnostic tumor grading and selective profiling in low-grade EC to increase cost-effectiveness

Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer

Inhibidores de la aromatasa; Terapia de progestinaAromatase inhibitors; Progestin therapyInhibidors de l'aromatasa; Teràpia amb progestinaBackground Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. Objective This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. Study Design Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction–based messenger RNA model to measure the activity of estrogen receptor–related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. Results Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9–43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2–64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9–68.9) and 75.0% (95% confidence interval, 62.2–87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1–73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20–48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20–52) with an estrogen receptor pathway activity score of >15 had not progressed. Conclusion The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study

Ovarian Cyst Fluid of Serous Ovarian Tumors Contains Large Quantities of the Brain Amino Acid N-acetylaspartate

BACKGROUND: In humans, N-acetyl L-aspartate (NAA) has not been detected in other tissues than the brain. The physiological function of NAA is yet undefined. Recently, it has been suggested that NAA may function as a molecular water pump, responsible for the removal of large amounts of water from the human brain. Ovarian tumors typically present as large cystic masses with considerable fluid accumulation. METHODOLOGY AND PRINCIPAL FINDINGS: Using Gas Chromatography-Mass Spectrometry, we demonstrated that NAA was present in a high micromolar concentration in oCF of epithelial ovarian tumors (EOTs) of serous histology, sometimes in the same range as found in the extracellular space of the human brain. In contrast, oCF of EOTs with a mucinous, endometrioid and clear cell histological subtype contained a low micromolar concentration of NAA. Serous EOTs have a cellular differentiation pattern which resembles the lining of the fallopian tube and differs from the other histological subtypes. The NAA concentration in two samples of fluid accumulation in the fallopian tube (hydrosalpinx) was in the same ranges as NAA found in oCF of serous EOTs. The NAA concentration in oCF of patients with serous EOTs was mostly 10 to 50 fold higher than their normal serum NAA concentration, whereas in patients with other EOT subtypes, serum and cyst fluid NAA concentration was comparable. CONCLUSIONS AND SIGNIFICANCE: The high concentration of NAA in cyst fluid of serous EOTs and low serum concentrations of NAA in these patients, suggest a local production of NAA in serous EOTs. Our findings provide the first identification of NAA concentrations high enough to suggest local production outside the human brain. Our findings contribute to the ongoing research understanding the physiological function of NAA in the human body

Preoperative CA125 Significantly Improves Risk Stratification in High-Grade Endometrial Cancer

Advanced stage; Endometrial cancer; OutcomeEtapa avançada; Càncer d'endometri; ResultatEtapa avanzada; Cáncer de endometrio; ResultadoPatients with high-grade endometrial carcinoma (EC) have an increased risk of tumor spread and lymph node metastasis (LNM). Preoperative imaging and CA125 can be used in work-up. As data on cancer antigen 125 (CA125) in high-grade EC are limited, we aimed to study primarily the predictive value of CA125, and secondarily the contributive value of computed tomography (CT) for advanced stage and LNM. Patients with high-grade EC (n = 333) and available preoperative CA125 were included retrospectively. The association of CA125 and CT findings with LNM was analyzed by logistic regression. Elevated CA125 ((>35 U/mL), (35.2% (68/193)) was significantly associated with stage III-IV disease (60.3% (41/68)) compared with normal CA125 (20.8% (26/125), [p < 0.001]), and with reduced disease-specific—(DSS) (p < 0.001) and overall survival (OS) (p < 0.001). The overall accuracy of predicting LNM by CT resulted in an area under the curve (AUC) of 0.623 (p < 0.001) independent of CA125. Stratification by CA125 resulted in an AUC of 0.484 (normal), and 0.660 (elevated). In multivariate analysis elevated CA125, non-endometrioid histology, pathological deep myometrial invasion ≥50%, and cervical involvement were significant predictors of LNM, whereas suspected LNM on CT was not. This shows that elevated CA125 is a relevant independent predictor of advanced stage and outcome specifically in high-grade EC