The evolving role of MUC16 (CA125) in the transformation of ovarian cells and the progression of neoplasia.

MUC16 (the cancer antigen CA125) is the most commonly used serum biomarker in epithelial ovarian cancer, with increasing levels reflecting disease progression. It is a transmembrane glycoprotein with multiple isoforms, undergoing significant changes through the metastatic process. Aberrant glycosylation and cleavage with overexpression of a small membrane-bound fragment consist MUC16-related mechanisms that enhance malignant potential. Even MUC16 knockdown can induce an aggressive phenotype but can also increase susceptibility to chemotherapy. Variable MUC16 functions help ovarian cancer cells avoid immune cytotoxicity, survive inside ascites and form metastases. This review provides a comprehensive insight into MUC16 transformations and interactions, with description of activated oncogenic signalling pathways, and adds new elements on the role of its differential glycosylation. By following the journey of the molecule from pre-malignant states to advanced stages of disease it demonstrates its behaviour, in relation to the phenotypic shifts and progression of ovarian cancer. Additionally, it presents proposed differences of MUC16 structure in normal/benign conditions and epithelial ovarian malignancy.

Detection of ovarian cancer (± neo-adjuvant chemotherapy effects) via ATR-FTIR spectroscopy: comparative analysis of blood and urine biofluids in a large patient cohort.

Ovarian cancer remains the most lethal gynaecological malignancy, as its timely detection at early stages remains elusive. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy of biofluids has been previously applied in pilot studies for ovarian cancer diagnosis, with promising results. Herein, these initial findings were further investigated by application of ATR-FTIR spectroscopy in a large patient cohort. Spectra were obtained by measurements of blood plasma and serum, as well as urine, from 116 patients with ovarian cancer and 307 patients with benign gynaecological conditions. A preliminary chemometric analysis revealed significant spectral differences in ovarian cancer patients without previous chemotherapy (n = 71) and those who had received neo-adjuvant chemotherapy-NACT (n = 45), so these groups were compared separately with benign controls. Classification algorithms with blind predictive model validation demonstrated that serum was the best biofluid, achieving 76% sensitivity and 98% specificity for ovarian cancer detection, whereas urine exhibited poor performance. A drop in sensitivities for the NACT ovarian cancer group in plasma and serum indicates the potential of ATR-FTIR spectroscopy to identify chemotherapy-related spectral changes. Comparisons of regression coefficient plots for identification of biomarkers suggest that glycoproteins (such as CA125) are the main classifiers for ovarian cancer detection and responsible for smaller differences in spectra between NACT patients and benign controls. This study confirms the capacity of biofluids' ATR-FTIR spectroscopy (mainly blood serum) to diagnose ovarian cancer with high accuracy and demonstrates its potential in monitoring response to chemotherapy, which is reported for the first time. ATR-FTIR spectroscopy of blood serum achieves good segregation of ovarian cancers from benign controls, with attenuation of differences following neo-adjuvant chemotherapy.

A comparative analysis of different biofluids towards ovarian cancer diagnosis using Raman microspectroscopy.

Biofluids, such as blood plasma or serum, are currently being evaluated for cancer detection using vibrational spectroscopy. These fluids contain information of key biomolecules, such as proteins, lipids, carbohydrates and nucleic acids, that comprise spectrochemical patterns to differentiate samples. Raman is a water-free and practically non-destructive vibrational spectroscopy technique, capable of recording spectrochemical fingerprints of biofluids with minimum or no sample preparation. Herein, we compare the performance of these two common biofluids (blood plasma and serum) together with ascitic fluid, towards ovarian cancer detection using Raman microspectroscopy. Samples from thirty-eight patients were analysed (n = 18 ovarian cancer patients, n = 20 benign controls) through different spectral pre-processing and discriminant analysis techniques. Ascitic fluid provided the best class separation in both unsupervised and supervised discrimination approaches, where classification accuracies, sensitivities and specificities above 80% were obtained, in comparison to 60-73% with plasma or serum. Ascitic fluid appears to be rich in collagen information responsible for distinguishing ovarian cancer samples, where collagen-signalling bands at 1004 cm-1 (phenylalanine), 1334 cm-1 (CH3CH2 wagging vibration), 1448 cm-1 (CH2 deformation) and 1657 cm-1 (Amide I) exhibited high statistical significance for class differentiation (P < 0.001). The efficacy of vibrational spectroscopy, in particular Raman spectroscopy, combined with ascitic fluid analysis, suggests a potential diagnostic method for ovarian cancer. Raman microspectroscopy analysis of ascitic fluid allows for discrimination of patients with benign gynaecological conditions or ovarian cancer.

The impact of socioeconomic deprivation on mortality in cervical cancer patients in Cornwall (England).

OBJECTIVES: To assess the association between risk factors, including socioeconomic deprivation, and mortality, recurrence and chemo- or radiation toxicity in cervical cancer patients. METHODS: Retrospective study of cervical cancer patients diagnosed between January 2007 and July 2018. Patient characteristics and mortality data, including recurrence, were assessed, together with socioeconomic deprivation measures evaluated using the English Indices of Multiple Deprivation. Markov multi-state models were used to model mortality and recurrence, and logistic regression models were used to model chemo- or radiation toxicity. RESULTS: Included were 243 women with a median age of 49 years. A total of 57 patients died (23%), of which 41 due to cervical cancer, and 21 (9%) had recurrent disease. Hazard ratios (HR) showed no evidence of association between socioeconomic deprivation and cancer-specific hazard of mortality from diagnosis or recurrence, hazard of mortality due to other causes or hazard of cancer recurrence. Furthermore, there was no evidence of association between socioeconomic deprivation and chemo- or radiation toxicity (bowel, bladder or vaginal stenosis). CONCLUSIONS: No associations were found between socioeconomic deprivation and cancer mortality or recurrence in cervical cancer patients in the population of Cornwall. In addition, no association was found between socioeconomic deprivation and chemo- or radiation toxicity.

A three-dimensional discriminant analysis approach for hyperspectral images.

Raman hyperspectral imaging is a powerful technique that provides both chemical and spatial information of a sample matrix being studied. The generated data are composed of three-dimensional (3D) arrays containing the spatial information across the x- and y-axis, and the spectral information in the z-axis. Unfolding procedures are commonly employed to analyze this type of data in a multivariate fashion, where the spatial dimension is reshaped and the spectral data fits into a two-dimensional (2D) structure and, thereafter, common first-order chemometric algorithms are applied to process the data. There are only a few algorithms capable of working with the full 3D array. Herein, we propose new algorithms for 3D discriminant analysis of hyperspectral images based on a three-dimensional principal component analysis linear discriminant analysis (3D-PCA-LDA) and a three-dimensional discriminant analysis quadratic discriminant analysis (3D-PCA-QDA) approach. The analysis was performed in order to discriminate simulated and real-world data, comprising benign controls and ovarian cancer samples based on Raman hyperspectral imaging, in which 3D-PCA-LDA and 3D-PCA-QDA achieved far superior performance than classical algorithms using unfolding procedures (PCA-LDA, PCA-QDA, partial lest squares discriminant analysis [PLS-DA], and support vector machines [SVM]), where the classification accuracies improved from 66% to 83% (simulated data) and from 50% to 100% (real-world dataset) after employing the 3D techniques. 3D-PCA-LDA and 3D-PCA-QDA are new approaches for discriminant analysis of hyperspectral images multisets to provide faster and superior classification performance than traditional techniques.

Raman spectroscopy of blood and urine liquid biopsies for ovarian cancer diagnosis: identification of chemotherapy effects.

Blood plasma and serum Raman spectroscopy for ovarian cancer diagnosis has been applied in pilot studies, with promising results. Herein, a comparative analysis of these biofluids, with a novel assessment of urine, was conducted by Raman spectroscopy application in a large patient cohort. Spectra were obtained through samples measurements from 116 ovarian cancer patients and 307 controls. Principal component analysis identified significant spectral differences between cancers without previous treatment (n = 71) and following neo-adjuvant chemotherapy (NACT), (n = 45). Application of five classification algorithms achieved up to 73% sensitivity for plasma, high specificities and accuracies for both blood biofluids, and lower performance for urine. A drop in sensitivities for the NACT group in plasma and serum, with an opposite trend in urine, suggest that Raman spectroscopy could identify chemotherapy-related changes. This study confirms that biofluids' Raman spectroscopy can contribute in ovarian cancer's diagnostic work-up and demonstrates its potential in monitoring treatment response.

Laparoscopic salpingo-oophorectomy for ovarian ablation in women with hormone-sensitive breast cancer.

OBJECTIVE: To evaluate institutional experiences regarding laparoscopic salpingo-oophorectomy in breast cancer patients and to compare the technique with gonadotropin-releasing hormone (GnRH) analogs among premenopausal women with hormone-sensitive breast cancer. METHODS: Between 2004 and 2009, 103 women with breast cancer underwent laparoscopic salpingo-oophorectomy at Addenbrooke's Hospital, Cambridge, UK. All relevant medical records-including reasons for salpingo-oophorectomy, peri-operative events, and subsequent follow-up-were reviewed. RESULTS: In the study period, 3 (2.9%) women experienced a recurrence of breast cancer but none had primary peritoneal/ovarian cancer within a median follow-up interval of 34 months (range, 0-70 months). No operative complications were noted among these women and all of them went home on the day of their operation. CONCLUSION: Laparoscopic salpingo-oophorectomy seems to be a safe, permanent, and cost-effective method of ovarian ablation compared with the use of GnRH analogs. Salpingo-oophorectomy also considerably reduces the risk of subsequent ovarian/fallopian tube malignancy in this high-risk population.

Age-related differential diagnosis of vaginal bleeding in postmenopausal women: a series of 3047 symptomatic postmenopausal women.

OBJECTIVE: The aim of this study is to identify the causes of vaginal bleeding in different age groups of postmenopausal women. Also, we attempt to estimate the incidence of postmenopausal vaginal bleeding and endometrial cancer in a defined geographical area. STUDY DESIGN: The study was conducted at a gynaecological oncology centre in the United Kingdom, between February 2006 and May 2009. Patients were investigated according to established evidence-based departmental guidelines. RESULTS: During the study period 3047 women were referred with postmenopausal vaginal bleeding. In 1356 women (44.5%) the endometrial thickness measured less than 5 mm on transvaginal ultrasound scan. Benign histology was found in 1144 women (37.5%). Benign endometrial polyps were the cause of bleeding in 10.1% of the cases. The incidence of endometrial cancer in our study population was 5%. The rate of postmenopausal vaginal bleeding during the study period peaks at the age of 55-59 years (25.9/1000 postmenopausal women/year) and declines thereafter. The peak incidence of endometrial cancer during the study period (12.6/10,000 postmenopausal women/year) was seen between the ages of 60 and 64 years and similarly declines with increasing age. CONCLUSION: To our knowledge, this is the first population-based estimation of the incidence of genital tract bleeding and endometrial cancer among postmenopausal women in the United Kingdom. The results of this study showing the age-related differential diagnosis can be used to inform clinical practice when counselling postmenopausal women with vaginal bleeding.