Jitka Hausnerová

Cytological and Immunocytochemistry Findings in Fallopian Tube Brush Specimens and Their Correlation With Histology

ABSTRACTContextHigh‐grade serous carcinoma (HGSC), the most prevalent and lethal form of ovarian cancer, is increasingly recognised to originate in the fimbrial end of the fallopian tube (FT). Timely detection remains a critical unmet clinical need due to ineffective screening methods. This prospective observational study assesses the diagnostic potential of FT brush cytology by correlating cytomorphological and immunocytochemical findings with histologically confirmed HGSC.Methods and MaterialA total of 134 FT from 89 patients undergoing salpingo‐oophorectomy (with or without hysterectomy) were analysed. Liquid‐based cytology samples were evaluated for morphological abnormalities and subjected to immunocytochemistry using p53 and Ki‐67 markers. Cytological results were classified as benign, suspicious or malignant. Statistical analyses included sensitivity, specificity and odds ratio calculations via logistic regression (α = 0.05), performed using the R software.ResultsHistopathology confirmed HGSC in 15 patients. Of these, brush cytology identified 12 as suspicious or malignant, demonstrating high diagnostic concordance. Aberrant p53 expression was found in 11 cases, and a high Ki‐67 proliferation index was observed in 10. These findings underscore the strong correlation between cytological, immunocytochemical and histological features of tubal HGSC.ConclusionsIn conclusion, FT brush cytology combined with p53 and Ki‐67 immunocytochemistry shows promise as a minimally invasive approach for early HGSC detection. Future research should focus on larger prospective cohorts, ideally incorporating in vivo hysteroscopic sampling.

Improving pre-operative binary grading: relevance of p53 and PR expression in grade 2 endometrioid endometrial carcinoma

This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas. Three European endometrial carcinoma cohort studies were included. Patients with pre-operative grade 2 endometrioid carcinoma and known pre-operative PR and p53 status were included (n = 400), as were patients with pre-operative grade 1 (n = 602) or grade 3 (n = 148) endometrioid carcinomas. Kaplan-Meier and Cox regression analyses were performed to analyze disease-specific and disease-free survival. Patients with pre-operative grade 2 endometrial carcinoma and wild-type p53 plus PR-positive expression showed a similar 7-year disease-specific survival to grade 1 endometrial carcinoma patients (95.8% vs 97.5%, p = .13), while the 7-year disease-specific survival of patients with grade 2 endometrial carcinoma with p53 aberrant and/or negative PR expression (83.5%) was significantly lower (p < .001). The combination of these markers was an independent prognostic factor in multivariate Cox regression analyses. The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression.

LAMP‐based electrochemical platform for monitoring HPV genome integration at the mRNA level associated with higher risk of cervical cancer progression

AbstractHuman papillomaviruses (HPVs) represent a diverse group of double‐stranded DNA viruses associated with various types of cancers, notably cervical cancer. High‐risk types of HPVs exhibit their oncogenic potential through the integration of their DNA into the host genome. This integration event contributes significantly to genomic instability and the progression of malignancy. However, traditional detection methods, such as immunohistochemistry or PCR‐based assays, face inherent challenges, and thus alternative tools are being developed to fasten and simplify the analysis. Our study introduces an innovative biosensing platform that combines loop‐mediated amplification with electrochemical (EC) analysis for the specific detection of HPV16 integration. By targeting key elements like the E7 mRNA, a central player in HPV integration, and the E2 viral gene transcript lost upon integration, we show clear distinction between episomal and integrated forms of HPV16. Our EC data confirmed higher E7 expression in HPV16‐positive cell lines having integrated forms of viral genome, while E2 expression was diminished in cells with fully integrated genomes. Moreover, we revealed distinct expression patterns in cervical tissue of patients, correlating well with digital droplet PCR, qRT‐PCR, or immunohistochemical staining. Our platform thus offers insights into HPV integration in clinical samples and facilitates further advancements in cervical cancer research and diagnostics.

TRPS1 expression in 451 tubo-ovarian tumours: a potential prognostic marker for high-grade serous carcinoma.

Trichorhinophalangeal syndrome type 1; transcriptional repressor GATA binding 1 (TRPS1), a member of the GATA transcription factor family, functions primarily as a transcriptional repressor. TRPS1 is frequently utilised as a diagnostic marker for breast carcinoma, although its specificity is lower than previously believed. Moreover, TRPS1 is expressed in various solid tumours originating from the skin, salivary glands, soft tissues, prostate, urothelium, and female genital tract. The current study evaluated the diagnostic and prognostic significance of TRPS1 in 451 primary tubo-ovarian tumours. The cohort included 94 high-grade serous carcinomas (HGSCs), 81 low-grade serous carcinomas (LGSCs), 31 micropapillary serous borderline tumours (mSBTs), 92 clear cell carcinomas (CCCs), 52 endometrioid carcinomas (ECs), 31 mucinous carcinomas (MCs), and 70 mucinous borderline tumours (MBTs). Immunohistochemical analysis was performed using tissue microarrays following standardised protocols. Clinical data were analysed to determine the prognostic relevance of TRPS1 expression. TRPS1 expression was detected in 47% of HGSCs, 44% of ECs, 35% of CCCs, 19% of LGSCs, and 29% of mSBTs with complete negativity in MC/MBT. TRPS1-negative HGSC cases had higher recurrence rates than those with positive staining. Furthermore, TRPS1 expression significantly correlated with improved metastasis-free survival in HGSC cases. These findings suggest that TRPS1 may serve as an independent prognostic marker for HGSC. Despite varying expression rates across primary tubo-ovarian carcinomas, the routine use of TRPS1 in the differential diagnosis seems to be limited, ​as other robust immunohistochemical markers are available for distinguishing the individual subgroups. Further research is needed to clarify the specific functions and clinical implications of TRPS1 in tubo-ovarian cancer.

ENDORISK-2: A personalized Bayesian network for preoperative risk stratification in endometrial cancer, integrating molecular classification and preoperative myometrial invasion assessment

ENDORISK is a Bayesian network that can assist in preoperative risk estimation of lymph node metastasis (LNM) risk in endometrial cancer (EC) with consistent performance in external validations. To reflect state of the art care, ENDORISK was optimized by integrating molecular classification and preoperative assessment of myometrial invasion (MI). Variables for POLE, MSI, and preoperative assessment of MI, either by expert transvaginal ultrasound or pelvic magnetic resonance imaging (MRI), were added to develop ENDORISK-2. The p53 biomarker, part of the molecular classification, was already included in ENDORISK. External validation of ENDORISK-2 for LNM prediction was performed in two independent cohorts from: Brno (CZ), (n = 581) and Tübingen (DE), (n = 247). ENDORISK-2 yielded AUCs of 0·85 (95 % CI 0·80-0·90) (CZ) and 0·86 (95 % CI 0·77-0·96) (DE) for predicting LNM. In patients with low-grade histology, 83 % (CZ) and 89 % (DE) were estimated having less than 10 % risk of LNM, with false negative rates (FNR) of 4·3 % (CZ) and 2·2 % (DE). The previously defined set of minimally required variables, i.e.: preoperative tumor grade, three of the four immunohistochemical (IHC) markers, and one clinical marker, could be interchanged with the new variables, with comparable validation metrics, including AUC values of 0·79-0·87 for LNM prediction. Incorporation of molecular data and preoperative MI improved the flexibility of ENDORISK with comparable diagnostic accuracy for estimating LNM as when based on low-cost immunohistochemical biomarkers. In addition, the high diagnostic accuracy in patients with low-grade EC demonstrates how ENDORISK-2 could aid clinicians in identifying patients in whom surgical lymph node assessment may safely be omitted. These results underline its power for clinical use in both high and low resource countries.