Carbohydrate sulfotransferases (CHST) catalyse the biosynthesis of proteoglycans that enable physical interactions and signalling between different neighbouring cells in physiological and pathological states. The study aim was to provide an overview of emerging diagnostic and prognostic applications of CHST. PubMed database search was conducted using the keywords \"carbohydrate sulfotransferase\" together with appropriate inclusion and exclusion criteria, whereby 41 publications were selected. Additionally, 40 records on CHST genetic and biochemical properties were hand-picked from UniProt, GeneCards, InterPro, and neXtProt databases. Carbohydrate sulfotransferases have been applied mainly in diagnostics of connective tissue disorders, cancer and inflammations. The lack of CHST activity was found in congenital connective tissue disorders while CHST overexpression was detected in different malignancies. Mutations of CHST3 gene cause skeletal dysplasia, chondrodysplasia, and autosomal recessive multiple joint dislocations while increased tissue expression of CHST11, CHST12 and CHST15 is an unfavourable prognostic factor in ovarian cancer, glioblastoma and pancreatic cancer, respectively. Recently, CHST11 and CHST15 overexpression in the vascular smooth muscle cells was linked to the severe lung pathology in COVID-19 patients. Promising CHST diagnostic and prognostic applications have been described but larger clinical studies and robust analytical procedures are required for the more reliable diagnostic performance estimations.

Cancer arising from adenomyosis is very rare, with transformation occurring in only 1% of cases and in older individuals. Adenomyosis, endometriosis and cancers may share a common pathogenic mechanism that includes hormonal factors, genetic predisposition, growth factors, inflammation, immune system dysregulation, environmental factors and oxidative stress. Endometriosis and adenomyosis both exhibit malignant behaviour. The most common risk factor for malignant transformation is prolonged exposure to oestrogens. The golden standard for diagnosis is histopathology. Colman and Rosenthal emphasised the most important characteristics in adenomyosis-associated cancer. Kumar and Anderson emphasised the importance of demonstrating a transition between benign and malignant endometrial glands in cancer arising from adenomyosis. As it is very rare, it is difficult to standardize treatment. In this manuscript, we try to emphasize some aspects regarding the management strategy, as well as how heterogenous the studies from the literature are in terms of prognosis in both cancers that develop from adenomyosis or those that are only associated with adenomyosis. The pathogenic mechanisms of transformation remain unclear. As these types of cancer are so rare, there is no standardised treatment. A novel target in the diagnosis and treatment of gynaecological malignancies associated with adenomyosis is also being studied for the development of new therapeutic concepts.

BACKGROUND: Ovarian cancer has a low incidence, but high mortality due to a habitual diagnosis in advanced cancer stages. Currently, used biomarkers have good sensitivity, but low specificity.
OBJECTIVE: To determine the usefulness of the biomarkers and algorithms used up to now in the screening, diagnosis, response to treatments and identification of recurrence in patients with ovarian masses.
METHODS: Systematic search of publications in English in the Medline-PubMed database with the terms: \"biomarkers\", \"tumour\", \"tumour biomarkers\", \"marker\", \"tumour marker\", \"ovarian cancer\", \"ovarian\", \"Neoplasms\", \"cancer\", CA-125 Antigen; Human Epididymis-specific Protein E4; Risk of Malignancy Index (RMI); Risk of Ovarian Malignancy Algorithm (ROMA); Ovarian Neoplasms. Original articles, clinical trials, reviews, systematic reviews and meta-analyses, published between January 2000 and November 2020, were selected to determine the usefulness (among others) of CA 125 and HE4 antigen in ovarian cancer.
RESULTS: Finally, 39 transcendental publications were selected to write this article to determine the usefulness of tumour markers and algorithms in ovarian cancer.
CONCLUSIONS: The usefulness of the tumour markers antigen CA125 and antigen HE4 individually or as a basis for decision-making algorithms has low specificity; however, there is little evidence that confirms their usefulness as markers in ovarian cancer screening.

BACKGROUND: Blood-borne tumour markers in the form of circulating tumour cells (CTCs) are of intense research interest in the diagnostic and prognostic work-up of hepatocellular carcinoma (HCC).
METHODS: This is a meta-analysis. Using a PICO strategy, adults with HCC was the population, with the individual CTCs as the intervention and comparators. The primary outcome was the sensitivity and specificity of HCC detection with tumour specific single gene methylation alteration. Secondary outcomes were the comparison using specific assay methods and the effect of early vs. late stages on CTC positivity. We included patients with HCC who had samples taken from peripheral blood and had sufficient data to assess the outcome data. ASSIA, Cochrane library, EMbase, Medline, PubMed and the knowledge network Scotland were systematically searched with appropriate Mesh terms employed. The quality assessment of diagnostic accuracy studies (QUADAS) was used to ensure quality of data. Statistical analysis was performed using the \'Rev Man\' meta-analysis soft ward for Windows.
RESULTS: The review included 36 studies, with a total of 5,853 patients. Here, we found that AFP has the highest overall diagnostic performance. The average Youden index amongst all CTC was 0.46 with a mode and median of 0.5 with highest of 0.87 and lowest of 0.01.
CONCLUSIONS: The available literature provides weak evidence that there is potential in the use of CTC, however the lack of a standardised procedure in the study of CTC contribute to the lack of consensus of use. Future research should include large scaled, standardized studies for the diagnostic accuracy of CTCs.

Estrogen receptors alpha (ERα) and beta (ERβ) and the cooperating protein GATA-binding factor 3 (GATA3) have been implicated in bladder carcinogenesis and tumour progression. GATA3 and ER have been functionally linked in the establishment of luminal fate in breast tissue, but to date their relationship in bladder cancer has not been established. This information will be useful to advance diagnostic and prognostic markers.
To determine the relationship between the expression of ERα, ERβ and GATA3 in bladder cancer, disclose their prognostic and diagnostic value and their association with clinicopathological characteristics.
A comprehensive literature search in PubMed database was performed for all immunohistochemical studies of ERα, ERβ and/or GATA3 in bladder cancer patients. We selected eligible studies in accordance with the PRISMA guidelines and evaluated methodological quality and risk of bias based on quality criteria from the reporting recommendations for tumour MARKer (REMARK) prognostic studies. Risk of bias assessment was performed using Review Manager 5. R software was used for all statistical analysis, the packages used were meta and dmetar for the standard meta-analysis, and netmeta for the network meta-analysis.
Thirteen studies were eligible for ERα, 5 for ERβ and 58 for GATA3 meta-analysis. Low grade tumours showed significantly lower ERα expression. GATA3 was widely expressed in bladder tumours, especially urothelial carcinomas, with higher expression of GATA3 in low grade and low stage tumours. Data was insufficient to determine the prognostic value of either ERα or ERβ, but GATA3-positivity was associated with higher recurrence free survival. A negative correlation between ERα or ERβ positivity and GATA3 expression was disclosed. Additionally, several sources of heterogeneity were identified, which can be used to improve future studies.
The clinicopathological value of ERα and ERβ was inconclusive due to low availability of studies using validated antibodies. Still, this meta-analysis supports GATA3 as good prognostic marker. On the contrary, ERα-positivity was associated to higher grade tumours; while ERα and ERβ were inversely correlated with GATA3 expression. Considering that it has previously been shown that bladder cancer cell lines have functional ERs, this suggests that ERα could be activated in less differentiated cells and independently of GATA3. Therefore, a comprehensive analysis of ERα and ERβ expression in BlaCa supported by complete patient clinical history is required for the identification of BlaCa subtypes and subgroups of patients expressing ERα, to investigate if they could benefit from treatment with hormonal therapy.
Prospero, CRD42021226836.

The coexistence of imperforate hymen and vaginal septum is rare and their ability to mimic malignant manifestations have not been frequently reported. This current case report describes a 13-year-old girl that presented with cyclic abdominal pain for 6 months. She was found to have a huge mass via abdominal plain film X-ray and sonography, with inexplicably high levels of serum carcinoembryonic antigen, cancer antigen (CA)-19-9 and CA-125. Pelvic computed tomography imaging disclosed two huge cystic lesions in the uterine and upper vaginal cavities. Surgical intervention conformed the diagnosis of a concurrent imperforate hymen and transverse vaginal septum, echoing the imaging findings of haematocolpometra. Her tumour marker levels gradually returned to normal after surgery. This rare case of concomitant imperforate hymen and transverse vaginal septum highlights that haematocolpometra, a benign disease that might mimic malignancy, should be taken into consideration in any adolescent females with an abdominal mass and amenorrhoea to ensure an early diagnosis and timely appropriate management.

Most adnexal masses are benign, incidental findings of pregnancy which resolve spontaneously. They may present clinically due to haemorrhage, rupture, torsion and mass effect. Aetiological classification includes ovarian benign, ovarian malignant, non-ovarian, gynaecological, non-ovarian non-gynaecological and an additional subset of pathologies unique to pregnancy. Ultrasound is the first-line imaging modality for the evaluation of adnexal masses. This may be supplemented with magnetic resonance imaging. Tumour markers support evaluation of malignant potential, but interpretation of results in pregnancy is challenging. Surgical intervention requires consideration of gestation, lesion characteristics and presence of complications. Laparoscopy is preferred owing to shorter operative time, quicker recovery and resultant lower thrombotic risk. Post-viability, fetal wellbeing and assessment must be considered. Management of the pregnancy may include cardiotocography, steroids, non-teratogenic antibiotics and tocolytics. In rare cases, particularly related to malignancy, termination of pregnancy may be required to enable immediate management where there are concerns for maternal wellbeing.

BACKGROUND: Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). A systematic review and meta-analysis of the published literature was carried out to summarise and analyse the evidence for discriminatory IHC biomarkers to differentiate the two entities.
METHODS: PubMed database was used to identify relevant literature. Primary end point was comparison of positive immunostaining of the biomarkers in chRCC and RO, with extracted data used to calculate OR and 95% CI and statistical I(2) test of heterogeneity for multiple studies.
RESULTS: One hundred and nine manuscripts were available for review. Data extracted were subjected to quantitative meta-analysis. Ten most effective biomarkers (OR of chRCC/RO and CI) are: amylase α1A (n=129, OR=0.001, 95% CI 0.0001 to 0.019); Wnt-5a (n=38, OR=0.0076, 95% CI 0.0004 to 0.015); FXYD2 (n=57, OR=130, 95% CI 14.2 to 1192.3); ankyrin-repeated protein with a proline-rich region (ARPP) (n=25, OR=0.0054, 95% CI 0.0002 to 0.12); cluster of differentiation 63 (CD63) (n=62, diffuse (chRCC) vs apical/polar (RO) stain pattern); transforming growth factor β 1 (TGFβ1) (n=34, membranous (chRCC) vs cytoplasmic (RO)); cytokeratin 7 (CK7) (11 studies, n=448, pooled OR=44.22, 95% CI 22.52 to 86.64, I(2)=15%); S100A1 (4 studies, n=124, pooled OR=0.01, 95% CI 0 to 0.03, I(2)=0%); caveolin-1 (2 studies, n=102, pooled OR=32.95, 95% CI 3.67 to 296.1, I(2)=70%) and claudin-7 (3 studies, n=89, pooled OR=24.7, 95% CI 6.28 to 97.1, I(2)=0%).
CONCLUSIONS: We recommend a panel of IHC biomarkers of amylase α1A, Wnt-5a, FXYD2, ARPP, CD63, TGFβ1, CK7, S100A1, caveolin-1 and claudin-7 to aid in the differentiation of chRCC and RO.