PTEN and Gynecological Cancers

PTEN is a tumour suppressor gene, and its loss of function is frequently observed in both heritable and sporadic cancers. It is involved in a great variety of biological processes, including maintenance of genomic stability, cell survival, migration, proliferation and metabolism. A better understanding of PTEN activity and regulation has therefore emerged as a subject of primary interest in cancer research. Gynaecological cancers are variously interested by PTEN deregulation and many perspective in terms of additional prognostic information and new therapeutic approaches can be explored. Here, we present the most significant findings on PTEN in gynaecological cancers (ovarian, endometrial, cervical, vulvar and uterine cancer) focusing on PTEN alterations incidence, biological role and clinical implications

Ovarian cancer beyond imaging: integration of AI and multiomics biomarkers

Abstract High-grade serous ovarian cancer is the most lethal gynaecological malignancy. Detailed molecular studies have revealed marked intra-patient heterogeneity at the tumour microenvironment level, likely contributing to poor prognosis. Despite large quantities of clinical, molecular and imaging data on ovarian cancer being accumulated worldwide and the rise of high-throughput computing, data frequently remain siloed and are thus inaccessible for integrated analyses. Only a minority of studies on ovarian cancer have set out to harness artificial intelligence (AI) for the integration of multiomics data and for developing powerful algorithms that capture the characteristics of ovarian cancer at multiple scales and levels. Clinical data, serum markers, and imaging data were most frequently used, followed by genomics and transcriptomics. The current literature proves that integrative multiomics approaches outperform models based on single data types and indicates that imaging can be used for the longitudinal tracking of tumour heterogeneity in space and potentially over time. This review presents an overview of studies that integrated two or more data types to develop AI-based classifiers or prediction models. Relevance statement Integrative multiomics models for ovarian cancer outperform models using single data types for classification, prognostication, and predictive tasks. Key points • This review presents studies using multiomics and artificial intelligence in ovarian cancer. • Current literature proves that integrative multiomics outperform models using single data types. • Around 60% of studies used a combination of imaging with clinical data. • The combination of genomics and transcriptomics with imaging data was infrequently used. Graphical Abstrac

Ovarian cancer beyond imaging: integration of AI and multiomics biomarkers

Acknowledgements: Figure 1 was created in the Mind the Graph platform (www.mindthegraph.com).High-grade serous ovarian cancer is the most lethal gynaecological malignancy. Detailed molecular studies have revealed marked intra-patient heterogeneity at the tumour microenvironment level, likely contributing to poor prognosis. Despite large quantities of clinical, molecular and imaging data on ovarian cancer being accumulated worldwide and the rise of high-throughput computing, data frequently remain siloed and are thus inaccessible for integrated analyses. Only a minority of studies on ovarian cancer have set out to harness artificial intelligence (AI) for the integration of multiomics data and for developing powerful algorithms that capture the characteristics of ovarian cancer at multiple scales and levels. Clinical data, serum markers, and imaging data were most frequently used, followed by genomics and transcriptomics. The current literature proves that integrative multiomics approaches outperform models based on single data types and indicates that imaging can be used for the longitudinal tracking of tumour heterogeneity in space and potentially over time. This review presents an overview of studies that integrated two or more data types to develop AI-based classifiers or prediction models. Relevance statement Integrative multiomics models for ovarian cancer outperform models using single data types for classification, prognostication, and predictive tasks. Key points • This review presents studies using multiomics and artificial intelligence in ovarian cancer. • Current literature proves that integrative multiomics outperform models using single data types. • Around 60% of studies used a combination of imaging with clinical data. • The combination of genomics and transcriptomics with imaging data was infrequently used. Graphical Abstract

Ovarian cancer beyond imaging: integration of AI and multiomics biomarkers.

High-grade serous ovarian cancer is the most lethal gynaecological malignancy. Detailed molecular studies have revealed marked intra-patient heterogeneity at the tumour microenvironment level, likely contributing to poor prognosis. Despite large quantities of clinical, molecular and imaging data on ovarian cancer being accumulated worldwide and the rise of high-throughput computing, data frequently remain siloed and are thus inaccessible for integrated analyses. Only a minority of studies on ovarian cancer have set out to harness artificial intelligence (AI) for the integration of multiomics data and for developing powerful algorithms that capture the characteristics of ovarian cancer at multiple scales and levels. Clinical data, serum markers, and imaging data were most frequently used, followed by genomics and transcriptomics. The current literature proves that integrative multiomics approaches outperform models based on single data types and indicates that imaging can be used for the longitudinal tracking of tumour heterogeneity in space and potentially over time. This review presents an overview of studies that integrated two or more data types to develop AI-based classifiers or prediction models.Relevance statement Integrative multiomics models for ovarian cancer outperform models using single data types for classification, prognostication, and predictive tasks.Key points• This review presents studies using multiomics and artificial intelligence in ovarian cancer.• Current literature proves that integrative multiomics outperform models using single data types.• Around 60% of studies used a combination of imaging with clinical data.• The combination of genomics and transcriptomics with imaging data was infrequently used

Ovarian cancer beyond imaging: integration of AI and multiomics biomarkers

Acknowledgements: Figure 1 was created in the Mind the Graph platform (www.mindthegraph.com).AbstractHigh-grade serous ovarian cancer is the most lethal gynaecological malignancy. Detailed molecular studies have revealed marked intra-patient heterogeneity at the tumour microenvironment level, likely contributing to poor prognosis. Despite large quantities of clinical, molecular and imaging data on ovarian cancer being accumulated worldwide and the rise of high-throughput computing, data frequently remain siloed and are thus inaccessible for integrated analyses. Only a minority of studies on ovarian cancer have set out to harness artificial intelligence (AI) for the integration of multiomics data and for developing powerful algorithms that capture the characteristics of ovarian cancer at multiple scales and levels. Clinical data, serum markers, and imaging data were most frequently used, followed by genomics and transcriptomics. The current literature proves that integrative multiomics approaches outperform models based on single data types and indicates that imaging can be used for the longitudinal tracking of tumour heterogeneity in space and potentially over time. This review presents an overview of studies that integrated two or more data types to develop AI-based classifiers or prediction models.Relevance statement Integrative multiomics models for ovarian cancer outperform models using single data types for classification, prognostication, and predictive tasks.Key points• This review presents studies using multiomics and artificial intelligence in ovarian cancer.• Current literature proves that integrative multiomics outperform models using single data types.• Around 60% of studies used a combination of imaging with clinical data.• The combination of genomics and transcriptomics with imaging data was infrequently used. Graphical Abstract</jats:p

Management of stage III and IVa uterine cancer

The prognosis of patients with advanced endometrial cancer is poor with limited therapeutic options. Nevertheless, the integration of molecular features in the clinico-pathological classification of endometrial cancer has significantly refined prognostic risk groups, representing a major breakthrough not only in the management of the disease but also in treatment perspectives. New therapeutic compounds such as target therapies, immunotherapy, and hormonal therapies have emerged for this clinical setting. Furthermore, molecular-driven clinical trials may improve significantly the efficacy of new treatments selecting those patients who are highly likely to respond. This review aims at describing the state of the art of advanced stage III-IVa endometrial cancer management, providing also the most interesting clinical perspectives

L1CAM Expression in Microcystic, Elongated, and Fragmented (MELF) Glands Predicts Lymph Node Involvement in Endometrial Carcinoma

Simple Summary L1CAM overexpression (&gt;= 10%) and the microcystic, elongated, and fragmented (MELF) pattern of invasion have previously been assessed as prognostic factors in endometrial carcinoma. We aimed to assess the relationship between L1CAM expression, MELF glands, and lymph node involvement in endometrial carcinoma, as all these factors are related to epithelial-to-mesenchymal transition. We evaluated L1CAM expression in 58 cases of uterine-confined, low-grade endometrioid carcinomas. We found that most cases (65.5%) expressed L1CAM in a limited manner to MELF glands. Cases with L1CAM expression in &gt;= 10% of the MELF component showed a significantly higher tendency to lymph node spread (p &lt; 0.001), even when adjusted for lymphovascular space invasion, depth of myometrial invasion and p53/mismatch repair status. On this account, L1CAM expression in the MELF component may stratify the prognosis and management in patients with uterine-confined, low-grade carcinomas. In endometrial carcinoma, both L1CAM overexpression and microcystic, elongated and fragmented (MELF) patterns of invasion have been related to epithelial-to-mesenchymal transition and metastatic spread. We aimed to assess the association between L1CAM expression, the MELF pattern, and lymph node status in endometrial carcinoma. Consecutive cases of endometrial carcinoma with MELF pattern were immunohistochemically assessed for L1CAM. Inclusion criteria were endometrioid-type, low-grade, stage T1, and known lymph node status. Uni- and multivariate logistic regression were used to assess the association of L1CAM expression with lymph node status. Fifty-eight cases were included. Most cases showed deep myometrial invasion (n = 42, 72.4%) and substantial lymphovascular space invasion (n = 34, 58.6%). All cases were p53-wild-type; 17 (29.3%) were mismatch repair-deficient. Twenty cases (34.5%) had positive nodes. No cases showed L1CAM positivity in &gt;= 10% of the whole tumor. MELF glands expressed L1CAM at least focally in 38 cases (65.5%). L1CAM positivity in &gt;= 10% of the MELF component was found in 24 cases (41.4%) and was the only significant predictor of lymph node involvement in both univariate (p &lt; 0.001) and multivariate analysis (p &lt; 0.001). In conclusion, L1CAM might be involved in the development of the MELF pattern. In uterine-confined, low-grade endometrioid carcinomas, L1CAM overexpression in MELF glands may predict lymph node involvement

Ovarian Cancer Treatments Strategy: Focus on PARP Inhibitors and Immune Check Point Inhibitors

Ovarian cancer treatment strategy is mainly based on three pillars: cytoreductive surgery, platinum-based chemotherapy, and targeted therapies. The latter in the last decade has provided a remarkable improvement in progression free patients and, hopefully, in overall survival. In particular, poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors exploit BRCA 1/2 mutations and DNA damage response deficiencies, which are believed to concern up to 50% of high grade epithelial ovarian cancer cases. While these agents have an established role in ovarian cancer treatment strategy in BRCA mutated and homologous recombination deficient patients, an appropriate predictive molecular test to select patients is lacking in clinical practice. At the same time, the impressive results of immunotherapy in other malignancies, have opened the space for the introduction of immune-stimulatory drugs in ovarian cancer. Despite immune checkpoint inhibitors as a monotherapy bringing only modest efficacy when assessed in pretreated ovarian cancer patients, the combination with chemotherapy, anti-angiogenetics, PARP inhibitors, and radiotherapy is believed to warrant further investigation. We reviewed literature evidence on PARP inhibitors and immunotherapy in ovarian cancer treatment

Assessment of preoperative nutritional status using {BIA}-derived phase angle ({PhA}) in patients with advanced ovarian cancer: Correlation with the extent of cytoreduction and complications

Objective. To investigate whether patients' altered body composition (measured with bioimpedentiometry), due to a poor nutritional status, predicts the incidence of no residual disease at primary debulking and the risk of complications in patients with newly-diagnosed advanced epithelial ovarian cancer (EOC).Methods. Data regarding patients with newly-diagnosed stage IIIC-IV EOC undergoing elective nutritional assessment between December 2016 and March 2017, were prospectively collected. Bioelectrical impedance analysis (BIA) with measurement of BIA-derived phase angle [PM] at 50 KHz, was accomplished. Only patients with disease which was considered resectable at staging laparoscopy were submitted to open primary cytoreduction. The rate of residual tumor (RT) = 0 and the incidence of complications were assessed.Results. Seventy patients were included. Fifty-two of them were submitted to primary cytoreduction (74.3%) and 48 (68.6% of the entire cohort, 92.3% of those who underwent primary debulking) had RT = 0 at the end of surgery. Median values of PM were significantly lower in patients with RT &gt; vs. =0 (4.7, range: 3.6-5.8 vs. 53, range: 4.2-6.8; p = 0.001). Twenty-four (out of the 52 operated) patients (462%) developed at least one complication. PhA was significantly lower in patients with vs. without complications (5, range: 3.6-6.4, vs. 5.4, range 4.5-6.8; p = 0.03). After multivariable analysis, Fagotti score and PM were the only independent predictors of residual disease (OR:13.56; 95%0:1.33-137.6; p = 0.027 and 924; 1.16-73.43; p = 0.036, respectively) and of any complication (OR:4.9;95%CI:1.17-20.6; p = 0.03 and 7.27; 1.45-36.4; p = 0.01, respectively).Conclusions. Derangement of body composition (likely due to disease-related malnutrition) expressed as a low phase angle, is an independent predictor of residual disease and peri-operative complications at the time of upfront cytoreduction for advanced EOC. (C) 2018 Elsevier Inc. All rights reserved

Targeting the hallmarks of ovarian cancer: The big picture

Objective As a result of relevant achievements in the field of translational research, several active drugs and multiple biological targets are available in ovarian cancer (OC). In this complex scenario, there is an urgent need to effectively summarize the available data in order to update conclusions, and outline perspectives. Methods The results in terms of target identification and drug development have been summarized using the well-known hallmarks of cancer firstly described, and recently modified by Hanahan and Weinberg [1-2]. Published data from clinical trials have been retrieved from PubMed, Embase, CINAHL and Cochrane database. Ongoing clinical trials were searched using clinicaltrials.gov web platform, and identified using NCT number. Results Genomic instability and angiogenesis are the most actively investigated hallmarks in high-grade serous OC, and the inhibition of tumor immune evasion appears as the emerging strategy for molecularly-driven therapy. Targeting sustained proliferative signaling through MEK and mTOR inhibitors seems the most promising approach in clear cell, and low-grade serous OC. Conclusions This substantial amount of data suggests that targeted therapies are already part of the clinical and therapeutic management of OC patients. The expectations of getting from translational research a better knowledge of tumor biology and therefore personalized drugs are high and worthy of maximum effort from referral centers