Monika Sobočan

Changes in the Extracellular Matrix in Endometrial and Cervical Cancer: A Systematic Review

Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.

Evaluation of Patient-Reported Symptoms and Functioning after Treatment for Endometrial Cancer

The overall survival of women with endometrial cancer is excellent after management. Different management strategies are associated with variable patient-reported outcomes (PROs). Evaluating PROs in the follow-up period can aid in better counseling and intervention for PRO improvement. This study aimed to evaluate the properties of the Slovenian translation of the EORTC QLQ-EN24 assessment scale. Women treated at the University Medical Centre Maribor, Slovenia, between January 2016 and December 2019 were invited to report their symptoms using the EORTC QLQ-EN24 questionnaire. Data were correlated with treatment modalities and clinical characteristics. The median age of participants in our study was 61 years old. PROs were not specific to therapy or clinical characteristics. Overall, women who more frequently reported gastrointestinal symptoms, muscular pain, or back pain also had statistically more frequently decreased levels of PROs in other assessed areas. Women who reported sexual or vaginal problems more often reported significantly poorer body images. Sexual activity within 4 weeks prior to completing the scale was reported by 39% of women. Sexual functioning assessments also showed important correlations between sexual interest, enjoyment, and activity. Individualized follow-ups addressing PROs should be offered to better address concerns and improve long-term outcomes in women with endometrial cancer.

The Role of CTNNB1 in Endometrial Cancer

Endometrial cancer (EC) is the most common gynaecologic malignancy in the developed countries. Recent evidence suggests that histopathological subtyping together with molecular subgrouping can lead to more accurate assessment of the risk profile for the patient. Clinical studies suggest the currently used molecular classification improves the risk assessment of women with endometrial cancer but does not explain the differences in recurrence profiles clearly. This could be improved by novel markers. One of such are mutations in the β-catenin (CTNNB1) gene, a frequently mutated gene in endometrial cancer. This shows mutations mostly at phosphorylation sites of the β-catenin and almost exclusively in the endometrial subgroup of no specific molecular profile. CTNNB1 mutations lead to alterations in the Wnt/β-catenin signalling pathway, involved in the carcinogenesis and progression of EC by inducing transcription of target genes, whose function is to regulate the cell cycle. Although tumours with mutations in CTNNB1 tend to have low-risk characteristics, they are related to worse outcomes with significantly increased rate of disease recurrence and lower overall survival.

Ultra-High-Risk Gestational Choriocarcinoma of the Ovary Associated with Ectopic Pregnancy

Gestational choriocarcinoma of the ovary is an exceptionally rare and highly aggressive tumor. Preoperative diagnosis of extrauterine choriocarcinoma is difficult due to nonspecific clinical presentation and its resemblance to ectopic pregnancy. Without molecular genetic analysis, it is not possible to reliably differentiate gestational from non-gestational choriocarcinoma. Here, we present a case of a 44-year-old woman who presented to our emergency department with complaints of pelvic pain, vaginal bleeding, and amenorrhea. Because of a recent history of conservatively managed ectopic pregnancy, the patient underwent emergency laparoscopy. Right-sided salpingo-oophorectomy was performed due to intraoperatively suspected ovarian ectopic pregnancy. Histopathology results revealed the diagnosis of ovarian choriocarcinoma of possible gestational origin. It was classified as FIGO stage IV and WHO ultra-high-risk, and she underwent multi-agent chemotherapy without major complications. She has remained in complete remission after a 12-month follow-up. Considering the rarity of this diagnosis, we conducted a literature review including all published cases of suspected gestational choriocarcinomas of the ovary. We conclude that due to the rarity of this entity, preoperative differentiating between ovarian ectopic pregnancy and ovarian choriocarcinoma is extremely challenging, and without molecular genetic analysis, it is not possible to identify the genetic origin of the tumor.