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OBJECTIVE: Molecular features are essential for estimating the risk of recurrence and impacting overall survival in patients with endometrial cancer. Additionally, the surgical procedure itself could be personalized based on the molecular characteristics of the tumor. This study aims to assess the feasibility of obtaining reliable molecular classification status from biopsy specimens collected during hysteroscopy to better modulate the appropriate surgical treatment. METHODS: This monocentric, retrospective, observational study was conducted on 106 patients who underwent a biopsy procedure followed by radical surgery for endometrial cancer, with concurrent molecular investigation. The molecular classification was determined through immunohistochemical staining for p53 and mismatch repair proteins, along with gene sequencing for POLE. RESULTS: Overall, 106 patients underwent molecular investigation, which was finally achieved on 99 patients (93.4%). Among these, the molecular analysis was conducted in 71 patients (67%) on the pre-operative endometrial biopsy and on the final uterine specimen in 28 patients (26.4%). Most of the endometrial biopsies were performed using Bettocchi hysteroscopy (66%). Molecular analysis was not possible in seven patients (6.6%), with six cases due to sample inadequacy and one case attributed to intra-mucosal carcinoma. The molecular results showed that the copy number low sub-group was the most common, and five cases of 'multiple classifiers' were observed in the low-risk category. CONCLUSION: Our experience in obtaining molecular information from biopsy samples underscores the feasibility and efficacy of this technique, even in small tissue samples. This capability helps define the prognostic group of patients, facilitates timely decision-making, and develops a personalized strategy for each patient.
Subject(s)
Endometrial Neoplasms , Precision Medicine , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/genetics , Endometrial Neoplasms/surgery , Retrospective Studies , Middle Aged , Aged , Biopsy , Prognosis , Adult , Aged, 80 and over , Feasibility StudiesABSTRACT
OBJECTIVE: The Moon has a noticeable influence on the Earth due to its gravity, the most visible manifestation of which are tides. We aimed to see if the Moon's daily cycle, like the Sun's, affects the prevalence and incidence of childbirth. METHODS: In this retrospective cohort study, we examined all deliveries at the Academic Hospital of Udine between 2001 and 2019. All consecutive singleton pregnancies with spontaneous labor and vaginal delivery were included. RESULTS: During the period, 13,349 singleton pregnancies with spontaneous labor and vaginal delivery were delivered in 6939 days. A significantly higher prevalence of deliveries was found with the Moon above the horizon (50.63% vs. 49.37%, p < 0.05). Moreover, during the day, there was a significantly higher prevalence of deliveries than during nighttime (53.74% vs. 45.79%, p < 0.05). Combining the Moon and Sun altitude, the majority of deliveries were registered when both were above the horizon (27.39% vs. 26.13%, 23.25%, or 23.24%, p < 0.05). These findings were confirmed in multivariate analysis after adjusting for parity, gestational age, or season. We found no correlation between birth and the Moon phase. CONCLUSIONS: Our data support the interaction of the Moon and the Sun in determining the time of birth. More research is needed to understand these phenomena and improve our understanding of labor initiation mechanisms.
Subject(s)
Birth Rate , Moon , Humans , Female , Retrospective Studies , Pregnancy , Adult , Birth Rate/trends , Sunlight , Delivery, Obstetric/statistics & numerical data , Delivery, Obstetric/methods , ParturitionABSTRACT
INTRODUCTION: The study aimed to validate the Betella algorithm, focusing on molecular analyses exclusively for endometrial cancer patients, where molecular classification alters risk assessment based on ESGO/ESTRO/ESP 2020 guidelines. MATERIALS AND METHODS: Conducted between March 2021 and March 2023, the retrospective research involved endometrial cancer patients undergoing surgery and comprehensive molecular analyses. These included p53 and mismatch repair proteins immunohistochemistry, as well as DNA sequencing for POLE exonuclease domain. We applied the Betella algorithm to our population and evaluated the proportion of patients in which the molecular analysis changed the risk class attribution. RESULTS: Out of 102 patients, 97 % obtained complete molecular analyses. The cohort exhibited varying molecular classifications: 10.1 % as POLE ultra-mutated, 30.3 % as mismatch repair deficient, 11.1 % as p53 abnormal, and 48.5 % as non-specified molecular classification. Multiple classifiers were present in 3 % of cases. Integrating molecular classification into risk group calculation led to risk group migration in 11.1 % of patients: 7 moved to lower risk classes due to POLE mutations, while 4 shifted to higher risk due to p53 alterations. Applying the Betella algorithm, we can spare the POLE sequencing in 65 cases (65.7 %) and p53 immunochemistry in 17 cases (17.2 %). CONCLUSION: In conclusion, we externally validated the Betella algorithm in our population. The application of this new proposed algorithm enables assignment of the proper risk class and, consequently, the appropriate indication for adjuvant treatment, allowing for the rationalization of the resources that can be allocated otherwise, not only for the benefit of settings with low resources, but of all settings in general.
Subject(s)
Algorithms , DNA Polymerase II , Endometrial Neoplasms , Tumor Suppressor Protein p53 , Humans , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Female , Retrospective Studies , Middle Aged , Aged , Tumor Suppressor Protein p53/genetics , DNA Polymerase II/genetics , Mutation , Immunohistochemistry , Poly-ADP-Ribose Binding Proteins/genetics , Risk Assessment/methods , DNA Mismatch Repair , Aged, 80 and over , Adult , Sequence Analysis, DNA/methodsABSTRACT
No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.
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Severe maternal and newborn morbidity and mortality associated with pre-eclampsia, which are caused partly by premature delivery, affect a factual proportion of pregnancies. Despite its prevalence, the underlying causes of pre-eclampsia remain elusive, with emerging evidence implicating the aryl hydrocarbon receptor (AhR) in its pathogenesis. This study sought to elucidate the involvement of the AhR and its associated pathway in pre-eclampsia by comparing placental components of the AhR pathway in pregnant individuals with and without pre-eclampsia. This case-control investigation was conducted at the University Hospital of Udine from May 2021 to February 2023. The AhR was assessed using immunohistochemistry and immunofluorescence, and its mRNA was evaluated using a Real-Time Quantitative Reverse Transcription PCR. Levels of mRNA expression were also estimated for other components of the AhR pathway (CYP1B1, IDO1, ARNT, TIPARP, S100A4, and AHRR). Our findings show decreased levels of expression of AhR, IDO1, ARNT, TiPARP, and S100A4 in the placental tissues of individuals with pre-eclampsia compared to controls (p < 0.05). The AhR exhibited a distinct localization within the syncytiotrophoblast (nuclei and cytoplasm) and CD45-positive cells (nuclei and cytoplasm). Furthermore, a significant positive correlation between the AhR and S100A4 (rho = 0.81) was observed in normal placentas, while CYP1B1 displayed a significant negative correlation with the AhR (rho = -0.72), within addition to its negative correlation with TiPARP (rho = -0.83). This study illuminates pre-eclampsia's molecular aberrations, suggesting new diagnostic, therapeutic, and mechanistic approaches. This study emphasizes the need for more research to validate and broaden these findings to improve the management of this complex pregnancy condition.
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This study examines 8-hydroxyguanine (8-oxo-Gua) staining in placental tissue samples based on fetal size at birth as well as its relationships with placental histology and other pregnancy variables. This prospective cohort study included women > 18 years with a singleton pregnancy, a live fetus, fluency in Italian, and delivery at term. A total of 165 pregnancies were included in the study. The nuclear syncytiotrophoblast 8-oxo-Gua staining score in LGA was substantially greater than in late FGR (p < 0.05), although the cytoplasm score was lower in SGA and LGA than in AGA (p < 0.05). Furthermore, a sex-specific pattern of 8-oxo-Gua staining was discovered in single-term placentas, with more oxidative damage found in the nuclei of syncytiotrophoblast cells and stromal and endothelial cells in AGA males compared to AGA females (p < 0.05). Second, the histological pattern of late FGR placentae differed by gender. Finally, a significant correlation (p < 0.05) was found between high-intensity 8-oxo-Gua staining in the cytoplasm of syncytiotrophoblast cells and thrombi in the chorionic plate or villi in males. On the other hand, female fetuses demonstrated a significant connection (p < 0.05) between high-intensity 8-oxo-Gua staining in endothelial and stromal cells and high birthweight MoM values. Our findings indicated a significant variation in the oxidative stress pattern between male and female placentae, implying that fetal growth is regulated differently in the two sexes.
Subject(s)
Endothelial Cells , Placenta , Infant, Newborn , Female , Pregnancy , Male , Humans , Prospective Studies , Immunohistochemistry , Endothelial Cells/pathology , Fetal Growth Retardation/pathology , Gestational Age , Fetal DevelopmentABSTRACT
Hepatoid carcinoma of the ovary (HCO) is a tumor that resembles, both histologically and cytologically, hepatocarcinoma (HCC) in a patient with a non-cirrhotic liver not involved by the disease. Hepatoid carcinoma is an extremely rare histologic subtype of ovarian cancer and should be distinguished from metastatic HCC. Here, we report the rare case of a 67-year-old woman with ovarian recurrence of HCC 12 years after first diagnosis. The patient was being followed by oncologists because she had been diagnosed with HCV-related HCC (Edmonson and Stainer grade 2, pT2 N0 M0, G2, V1) in 2009. She had undergone surgery for enlarged left hepatectomy to the 4th hepatic segment with cholecystectomy and subsequent placement of a Kehr drain. The preoperative alpha-fetoprotein (AFP) level was 8600 ng/mL, while the postoperative value was only 2.7 ng/mL. At the first diagnosis, no other localizations of the disease, including the genital tract, were found. At the time of recurrence, however, the patient was completely asymptomatic: her liver function was within normal limits with negative blood indices, except for an increased blood dosage of AFP (467 ng/mL), and CA125, which became borderline (37.4 IU/mL). The oncologist placed an indication for a thoracic abdominal CT scan, which showed that the residual liver was free of disease, and the presence of a formation with a solid-cystic appearance and some calcifications at the left adnexal site. The radiological findings were confirmed on level II gynecological ultrasound. The patient then underwent a radical surgery of hysterectomy, bilateral oophorectomy, pelvic peritonectomy, and omentectomy by a laparotomic approach, with the sending of intraoperative extemporaneous histological examination on the annexus site of the tumor mass, obtaining RT = 0. Currently, the patient continues her gyneco-oncology follow-up simultaneously clinically, in laboratory, and instrumentally every 4 months. Our study currently represents the longest elapsed time interval between first diagnosis and disease recurrence, as evidenced by current data in the literature. This was a rather unique and difficult clinical case because of the rarity of the disease, the lack of scientific evidence, and the difficulty in differentiating the primary hepatoid phenotype of the ovary from an ovarian metastasis of HCC. Several multidisciplinary meetings for proper interpretation of clinical and anamnestic data, with the aid of immunohistochemistry (IHC) on histological slides were essential for case management.
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OBJECTIVE: To evaluate the diagnostic performance of the one-step nucleic acid amplification (OSNA) method for the detection of sentinel lymph node (SLN) metastases in women with apparent early-stage endometrial cancer compared with standard ultrastaging. METHODS: Prospective, multicentric, interventional study. Patients with apparent early-stage endometrial cancer who underwent primary surgical staging with SLN mapping were included. SLNs were serially sectioned with 2 mm slices perpendicular to the longest axis of the node: the odd slices were submitted to ultrastaging, whereas the even slices were submitted to the OSNA analysis. Diagnostic performance was calculated taking ultrastaging as referral standard. RESULTS: Three-hundred and sixteen patients with 668 SLNs were included. OSNA assay detected 22 (3.3%) positive SLNs, of which 17 (2.5%) were micrometastases and 5 (0.7%) macrometastases, whereas ultrastaging detected 24 (3.6%) positive SLNs, of which 15 (2.2%) were micrometastases and 9 (1.3%) macrometastases (p=0.48). Regarding negative SLNs, OSNA detected 646 (96.7%) negative nodes, including 8 (1.2%) isolated tumor cells, while ultrastaging detected 644 (96.4%) negative nodes with 26 (3.9%) isolated tumor cells. Specificity of OSNA was 98.4% (95% CI 97.5 to 99.4), accuracy was 96.7% (95% CI 95.4 to 98.1), sensitivity was 50% (95% CI 30.0 to 70.0), while negative predictive value was 98.1% (95% CI 97.1 to 99.2). Discordant results were found in 22 SLNs (3.3%) corresponding to 20 patients (6.3%). These were 10 (1.5%) false-positive SLNs (all micrometastases): one (0.1%) of these was a benign epithelial inclusion at ultrastaging. There were 12 (1.8%) false-negative SLNs of OSNA, of which 9 (1.3%) were micrometastases and 3 (0.5%) macrometastases. Overall, 17/668 (2.5%) benign epithelial inclusions were detected at ultrastaging. CONCLUSION: The OSNA method had high specificity and high accuracy in detecting SLN metastasis in apparent early-stage endometrial cancer. The advantage of the OSNA method could be represented as the possibility to analyze the entire lymph node thus eliminating sampling bias.
Subject(s)
Breast Neoplasms , Endometrial Neoplasms , Nucleic Acids , Humans , Female , Lymphatic Metastasis/pathology , Sentinel Lymph Node Biopsy/methods , Prospective Studies , Neoplasm Micrometastasis/diagnosis , Neoplasm Micrometastasis/pathology , Lymph Nodes/pathology , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Breast Neoplasms/pathology , Neoplasm StagingABSTRACT
Endometrial cancer is the most common gynecological malignancy in Europe and its management involves a variety of health professionals. In recent years, big discoveries were made concerning the management of patients diagnosed with endometrial cancer, particularly in the field of molecular biology and minimally invasive surgery. This requires the continuous updating of guidelines and protocols over the years. In this paper, we aim to summarize and compare common points and disparities among protocols for management of patients diagnosed with endometrial cancer by leading international gynecological oncological societies. We therefore systematically report the parallel among the guidelines based on the various steps patients with endometrial cancer usually undergo. The comparison between American and European protocols revealed some relevant disparities, in particular regarding surgical staging, molecular biology application as a prognostic tool and follow up regimens. This could possibly cause differences in interpreting and applying protocols in clinical practice in small centers, leading to a lack of adherence to guidelines or even prompting a confusing mix of them.
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Our primary aim was to estimate the magnitude of stage I endometrial cancer (EC) survivors that could benefit from hormonal therapy (HT). Our secondary aims were to assess EC incidence in women below 50 and below 60 over the years, and analyze the overall survival and any influencing factors. We analyzed the endometrioid EC data from the Surveillance, Epidemiology, and End Results (SEER) program according to women's age, tumor stage, and grade. We analyzed the proportions of EC survivors below 50 and below 60 years of age and stratified those age groups by race. For age distribution and survival analysis SEER, 18 registries' research data (2000-2018) were analyzed. We analyzed the SEER 12 registries' research data (1992-2019) for incidence time trends. Our investigation found a 14% and 40% cumulative prevalence of stage I EC that occurs in women below 50 or 60 years, respectively. EC's prevalence has progressively risen in recent decades, but cancer-specific mortality remains low. The increasing number of women affected by EC in premenopause or early postmenopause face an 18 years-survival rate of 96.86% and 95.73%, respectively. A significant proportion of low-grade EC survivors can potentially benefit from HT treatment, and this requires awareness of other aspects of their health or quality of life, in addition to cancer treatments.
Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Female , Humans , Quality of Life , SEER Program , Endometrial Neoplasms/drug therapy , Carcinoma, Endometrioid/drug therapy , Carcinoma, Endometrioid/epidemiology , HormonesABSTRACT
Mesonephric-like adenocarcinomas (MLA) are rare neoplasms that arise in the uterine body and ovary and have been added to the World Health Organisation's recent 2020 classification of female genital cancers. The pathogenesis of MLA is unknown and it remains debated whether they represent mesonephric carcinomas (Wolffian) arising in the endometrium/ovary or endometrioid carcinomas (Müllerian) closely mimicking mesonephric carcinomas. Here we report the case of a 57-year-old woman with an initial misdiagnosis of endometrioid adenocarcinoma on diagnostic biopsy. The patient came to our clinical evaluation for the appearance of menometrorrhagia complicated by anemia for several months. Therefore, she underwent pelvic echo-flowmetry, with indication for diagnostic hysteroscopy with endometrial biopsy, which yielded a positive result for endometrioid endometrial adenocarcinoma. Following staging CT scan and targeted examinations on pulmonary findings, the patient underwent surgery with surprise of definitive diagnosis deponent for endometrial MLA. Our intention is to establish a brief review of the scientific evidence in the literature and the tools available for a correct histological diagnosis, in the light of the scant anatomopathological evidence. Our question gives rise to the motive for the publication: is immunohistochemistry the right way to resolve the diagnostic error at histology, which is usually the only source of diagnostic certainty? This case is intended to alert of diagnostic error that risked having the patient treated as a neoplasm with a favorable prognosis and low degree of aggressiveness instead of for a very aggressive and poor prognosis tumor such as MLA.
Subject(s)
Adenocarcinoma , Carcinoma, Endometrioid , Humans , Female , Middle Aged , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Carcinoma, Endometrioid/diagnosis , Carcinoma, Endometrioid/pathology , Immunohistochemistry , Endometrium/pathology , Biomarkers, TumorABSTRACT
Objective: High-grade serous ovarian carcinoma (HGSC) often presents lymph node involvement. According to the paths of lymphatic drainage, the most common site of nodal metastasis is in the aortic area. However, pelvic lymph nodes are also involved and inguinal metastases are less frequent. Methods: Our report concerns the case of a 78-year-old woman with an inguinal lymph node relapse of HGSC, with the prior positivity of a right inguinal lymph node, after the primary surgery. Ovaries and tubes were negative on histological examination. A comprehensive search of the literature published from January 2000 to October 2021 was conducted on PubMed and Scopus. The papers were selected following the PRISMA guidelines. Nine retrospective studies were evaluated. Results: Overall, 67 studies were included in the initial search. Applying the screening criteria, 36 articles were considered eligible for full-text reading of which, after applying the exclusion criteria, 9 studies were selected for the final analysis and included in the systematic review. No studies were included for a quantitative analysis. We divided the results according to the relapse location: loco-regional, abdominal, and extra-abdominal recurrence. Conclusions: Inguinal node metastasis is a rare but not unusual occurrence in HGSC. A reasonable level of suspicion should be maintained in patients with inguinal adenopathy and high CA125 values, especially in women with a history of gynecologic surgery, even in the absence of negative imaging for an ovarian origin.
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Survivin was previously associated with tumor stage and grade in ovarian cancer and interfered with the tumor's drug sensitivity. In addition, Survivin expression was found to be regulated by the Sonic hedgehog (Shh) pathway, Krüppel-like factor (KLF) family proteins, and p53 pathway. The main aim of this study was to assess the prognostic values of immunohistochemical expression of Survivin, Klf5, Klf11, Shh, p53, p21, and Mdm2 in a cohort of high-grade ovarian serous cancers. Other aims were comparison between high- and low-grade ovarian serous cancer and between platinum-resistant and the other cases. The last aim was to assess the correlations among the immunohistochemical expression of the studied proteins. Retrospective cohort study to assess immunohistochemical expression of Survivin, Klf5, Klf11, Shh, p53, p21, and Mdm2 in a tissue microarray of primary tumor samples among 73 women affected by high-grade ovarian serous cancer and 9 by low-grade ovarian serous cancer. Klf5 and Shh cytoplasmic staining were associated with short overall survival (HR 6.38, 95% CI 2.25-18.01, P < .05 and 2.25, 95% CI 1.19-4.23, P < .05, respectively). In addition, cytoplasmic Klf5 staining, high Klf11, and p53 nuclear staining were associated with platinum resistance (P < .05). Cytoplasmic Shh score was significantly correlated to the immunohistochemical expression of Klf5, Klf11, Mdm2, and Survivin. Our data highlight the possible role of Klf5 and Shh as prognostic markers, meanwhile confirming the role of the KLF family proteins and p53 in ovarian cancer drug resistance. Moreover, Shh appeared to play an important role in the intracellular network of ovarian neoplasia.
Subject(s)
Cystadenocarcinoma, Serous , Ovarian Neoplasms , Biomarkers, Tumor , Carcinoma, Ovarian Epithelial , Cystadenocarcinoma, Serous/pathology , Female , Hedgehog Proteins , Humans , Kruppel-Like Transcription Factors/metabolism , Ovarian Neoplasms/pathology , Retrospective Studies , Survivin/metabolism , Tumor Suppressor Protein p53/metabolismABSTRACT
Simple Summary: Implementing intraoperative assessment of sentinel lymph nodes by one-step nucleic acid amplification in early breast cancer can reduce the surgical burden to the patient and the costs to the health system. However, only limited data are available in terms of long-term disease-free survival and overall survival. Therefore, this study aims to compare disease-free survival and overall survival between one-step nucleic acid amplification, frozen section, and definitive histology. These results could impact the healthcare community, adding further proof to the body of evidence supporting the broader adoption of this innovative technology that enables a safe reduction in patient surgical burden and healthcare costs. Background: The one-step nucleic acid amplification (OSNA) system is a novel molecular technique, which consents to quick intraoperative detection of sentinel lymph node metastases by the amplification of cytokeratin 19 mRNA. Our study aims to evaluate the OSNA method in comparison with frozen section (FS) and definitive histological examination of the sentinel lymph node biopsy among early breast cancer patients considering disease-free survival (DFS) and overall survival (OS). Methods: In this study, we included all women who underwent sentinel lymph node biopsy (SLNB) for breast cancers classified as TNM stage I and II in our center between January 2005 and January 2017, and the follow-up was collected up to January 2019. We divided patients among three groups based on SLNB evaluation: definitive histological examination, intra-operative FS, or OSNA. Results: We included 2412 SLNBs: 727 by definitive histological examination, 697 by FS, and 988 by OSNA. Isolated tumor cells were found in 2.32% of cases, micrometastasis in 9.12%, and macrometastases in 13.64%. Surgical procedure duration was significantly shorter in OSNA than in FS (42.1 minutes ±5.1 vs. 70.1 minutes ±10.5, p <0.05). No significant differences have been observed among the three groups regarding OS, DSF, cumulative local, or distant metastases. In particular 5-year DFS was 96.38% in definitive histology (95% C.I. 95.02-97.75%), 96.37% in FS (95% C.I. 94.98-97.78%), and 96.51% in OSNA group (95% C.I. 95.32-97.72%). Conclusions: No difference in OS and DFS was found comparing OSNA, FS, and definitive histology. Furthermore, reduced operative time was found in the OSNA group.
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Albeit it does not have the highest venous thromboembolism (VTE) incidence compared to other neoplasms, breast cancer contributes to many VTE events because it is the most diagnosed tumor in women. We aim to analyze the occurrence and timing of VTE during the follow-up of patients who underwent breast surgery, the possible correlated factors, and the overall survival. This retrospective study included all female patients diagnosed with mammary pathology and surgically treated in our clinic between January 2002 and January 2012. Of 5039 women who underwent breast surgery, 1056 were found to have no evidence of malignancy, whereas 3983 were diagnosed with breast cancer. VTE rate resulted significantly higher in patients with invasive breast cancer than in women with benign breast disease or carcinoma in situ. Invasive cancers other than lobular or ductal were associated with a higher VTE rate. In addition, chronic hypertension, high BMI, cancer type, and evidence of metastasis turned out to be the most significant risk factors for VTE in women who underwent breast surgery. Moreover, VTE occurrence significantly impacted survival in invasive breast cancer patients. Compared to women with benign mammary pathology, VTE prevalence in women with breast cancer is significantly higher. The knowledge about the risk factors of VTE could be helpful as prognostic information, but also to eventually target preventive treatment strategies for VTE, as far as the co-existence of invasive breast cancer and VTE has a significantly negative impact on survival.
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BACKGROUND: Recent reports indicate the potential role of the stimulated by retinoic acid 6 (STRA6) protein in developing insulin resistance. The study's objective was to assess placental STRA6 expression and staining pattern in human pregnancy complicated by gestational diabetes mellitus (GDM). The expression pattern of further relevant genes involved in retinoid metabolism was also evaluated. METHODS: A retrospective case-control study on paraffin-embedded placental tissue. Twenty-two human pregnancies affected by GDM, namely, 11 insulin-treated (iGDM) and 11 diet-controlled (dGDM), were compared with 22 normal-developed pregnancies (controls). An RT-PCR was performed in a random sample of 18 patients (six iGDM, six dGDM, and six controls) to assess RNA expression of STRA6 and further markers of retinoid metabolism. A semi-quantitative intensity evaluation at immunohistochemistry was performed for STRA6 in all 44 recruited patients. RESULTS: STRA6 showed a decreased placental staining (9.09% vs. 68.18% positively stained samples, p < 0.05) and augmented RNA expression in dGDM patients than controls (ΔCT expression 0.473, IQR 0.403-0.566 vs. 0.149, IQR 0.092-0.276, p < 0.05). The protein staining pattern in patients affected by iGDM was comparable to controls. A reduced RNA expression of LPL, LRP1, VLDLR, and MTTP besides an augmented expression of LDLR was found in dGDM, while overexpression of LRP1 and LPL was found in iGDM patients. Unlike in the control group, significant positive correlations were found between RXRα and the proteins involved in the intracellular uptake of ROH, such as STRA6, LRP1, LRP2, and VLDLR. CONCLUSIONS: An altered placental expression and staining pattern of STRA6 were found in pregnancies complicated by GDM compared to the controls. These changes were coupled to an altered expression pattern of several other genes involved in the retinoid metabolism.
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Chorioamnionitis can be either an infection or a sterile inflammation. This study aims to analyze the prevalence of acute inflammatory lesions of the placenta, the association with a positive result of the microbiological examination, and the fetal-maternal outcomes. This retrospective study considered all single, consecutive pregnancies and their placental pathological examination during 2014-2017. The evidence of funisitis, chorionic vasculitis, and chorioamnionitis was assessed by a pathologist, including stage and grade. Moreover, maternal fever, placental microbiological examination, and neonatal outcomes were also recorded. Among the 5910 pregnancies in the considered period, 1770 had a placental pathological examination, and 358 (6.06%) had acute placental inflammation. Microbiological examination was performed in 125 cases, revealing 64 cases with a positive microbiological outcome. In the presence of acute placental inflammation, there was a higher rate of neonatal cardiopulmonary resuscitation, admission to neonatal intensive care unit, and postnatal death of the newborn. Multivariate analysis inferred that acute inflammation of membranes was a risk factor for neonatal cardiopulmonary resuscitation (OR 2.12; CI.95 1.36-3.31; p < 0.05), acute funisitis was a risk factor for admission to intensive neonatal care unit (OR 3.2; CI.95 1.67-6.12; p < 0.05), and chorionic vasculitis was a risk factor for postnatal death of the newborn (OR 5.38; CI.95 1.37-21.06; p < 0.05). The prevalence of chorioamnionitis was 6.06%, and about half of the cases were sterile inflammation. Chorioamnionitis was associated with higher rates of adverse fetal and neonatal outcomes; in particular, chorionic vasculitis was a risk factor for postnatal death.
Subject(s)
Pregnancy Complications/microbiology , Cohort Studies , Female , Humans , Infant , Inflammation/therapy , Intensive Care Units, Neonatal , Male , Placenta , Pregnancy , Pregnancy Complications/pathology , Pregnancy Complications/therapy , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Breast cancer chemoresistance is attributed to a wide variety of mechanisms, including autophagy. Transcription factor EB (TFEB) has been recently identified and characterized as one major regulator of autophagy and lysosomal genesis. OBJECTIVE: This study aims to evaluate the prognostic impact of TFEB and its pathway in breast cancer chemoresistance. METHODS: This retrospective study analyzes the expression of TFEB, CARM1, SIRT1, and Beclin-1 and the methylation of PITX2 in breast carcinoma. A group of breast cancer patients treated with chemotherapy, who relapsed within 12 months from treatment initiation, were compared to a sub-cohort of chemo-treated patients who did not recur within 12 months of follow-up. The expression of TFEB, CARM1, SIRT1, and Belcin-1 was analyzed using immunohistochemistry or RT-PCR on formalin-fixed paraffin-embedded samples. PITX2 methylation was tested with the diagnostic CE-marked kit Therascreen PITX2 RGQ PCR. In the final model, 136 cases of chemo-treated breast cancer were included. RESULTS: A higher TFEB and Beclin-1 expression correlate with shorter survival in patients with chemo-treated invasive breast cancer (respectively HR 3.46, CI.95 1.27-9.47, p < 0.05 and 7.11, CI.95 2.54-19.9). TFEB, CARM1, and SIRT1 are positively correlated with Beclin-1. The protein expression of SIRT1 is significantly associated with TFEB and CARM1 so that a very low SIRT1 expression (lower than the first quartile of the H-score distribution) correlates with a low expression of TFEB and CARM1 and with longer survival. SIRT1 seems to have a lower H-score in the basal-like and HER2-enriched tumors than the luminal subtypes. Beclin-1 and TFEB seem to have a higher H-score in the basal-like and HER2-enriched tumors than the luminal subtypes. PITX2 methylation analysis was feasible only in 65% of the selected samples, but no significant differences between cases and controls were found, and there was also no correlation with the expression of the TFEB pathway. CONCLUSIONS: TFEB, SIRT1, and Beclin-1 seem to have a potential prognostic significance in patients with chemo-treated breast cancer, likely because of their role in the regulation of autophagy. In addition, no correlation between TFEB and PITX2 methylation was found, likely because they perform two different roles within the autophagy process.
Subject(s)
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Beclin-1/metabolism , Breast Neoplasms/metabolism , Drug Resistance, Neoplasm , Homeodomain Proteins/metabolism , Protein-Arginine N-Methyltransferases/metabolism , Sirtuin 1/metabolism , Transcription Factors/metabolism , Aged , Aged, 80 and over , Autophagy/physiology , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Case-Control Studies , Chemotherapy, Adjuvant , Female , Humans , Immunohistochemistry , Methylation , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Prognosis , Receptor, ErbB-2/metabolism , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Tissue Array Analysis , Homeobox Protein PITX2ABSTRACT
OBJECTIVE: Accelerated placental maturation is regarded as a sign of vascular malperfusion and is often interpreted as a compensatory response by the placenta. In vitro embryo culture affects placental development. This study assessed placental maturation in spontaneous conceived and in vitro conceived pregnancies. METHODS: Retrospective cohort study on a single center between 2014 and 2017. For this study, preterm placentas of singleton pregnancies between 24 and 36 weeks were considered. Routine placental examinations were retrospectively reviewed. RESULTS: During the considered period, 423 placentas of singleton pregnancies were assessed. Three hundred ninety-six placentas were from spontaneous conception and 20 from in vitro fertilization and embryo transfer (IVF/ET). IVF/ET was significantly associated with accelerated villous maturation (AVM) and distal villous hypoplasia (DVH) (P<0.05). CONCLUSIONS: Placental AVM and DVH were significantly associated with in vitro fertilization in singleton pregnancies. This result supports the hypothesis that AVM is a compensatory response by the placenta to improve its transport capacity in specific settings such as in vitro fertilization.
ABSTRACT
BACKGROUND: Atypical polypoid adenomyoma (APA) is a rare uterine tumor typically found in fertile age and associated with infertility. Among young nullipara women, conservative treatment is proposed despite the high recurrence rate and the association with endometrial cancer.Our aim was to assess the risk of recurrence with different conservative treatments in fertile ages and the prevalence of malignant or pre-malignant associated lesions to better address an adequate patient counselling when treatment modalities are discussed. METHODS: This study is a systematic review and meta-analysis of case reports and case series about APA management and follow-up. A literature search was carried from Medline and Scopus for studies published from January 1, 1980 to December 31, 2018. RESULTS: We included 46 observational studies and 296 cases in fertile women. The prevalence of APA relapse was 44% (CI.95 33-57%) and was lower in cases treated with operative hysteroscopy (22%; CI.95 11-39%) than in cases treated with blind curettage and polypectomy (38%; CI.95 15-67%). The prevalence of the concomitant or during the follow-up diagnosis of endometrial carcinoma was 16% (CI.95 9-29%). The risk of cancer development during follow-up was significantly less in cases treated with histeroscopy (10.56% new cumulative diagnosis at 5 years follow up; CI.95 0-23.7%) than blind curettage and polypectomy (35.5% new cumulative diagnosis at 5 years; CI.95 11.65-52.92%; Pâ<â.05). Medical treatment with medroxyprogesterone acetate after surgery does not reduce APA recurrence. Pregnancy was observed in 79% cases in which the desire was expressed. CONCLUSION: This review suggests that conservative treatment performed by operative hysteroscopy is the optimal choice because it lowers the risk of recurrence, improves the accuracy of concomitant carcinoma or hyperplasia diagnosis, and leaves the possibility of future pregnancies.