This study assessed the prognostic value of HE4 marker measurements at various stages of first-line chemotherapy for ovarian cancer.
The study consisted of 90 ovarian cancer patients, including 48 ...women undergoing primary surgical treatment and 42 patients qualified for neoadjuvant chemotherapy. Each patient underwent HE4 and CA 125 level measurements at the time of diagnosis and subsequently as follows: after surgical treatment, after the third course of adjuvant chemotherapy, before interval cytoreductive surgery and after chemotherapy. The HE4 value was assessed based on the PSF, OS, DFS, surgical outcome, two-year survival and platinum sensitivity.
Preoperative HE4 levels were a predictor of platinum sensitivity (AUC- 0.644; p = 0.035) and DFS (AUC = 0.637; p = 0.0492). A univariate logistic regression analysis showed that serum HE4 significantly correlated with PFS (baseline results over median HR = 2.96, p = 0.0009; baseline over 75 percentile HR = 2.44, p = 0.0062; normalization after treatment HR = 0.46, p = 0.0125; 50% reduction before IDS HR = 0.64, p = 0.0017). In the multivariate analysis, normalization after treatment and 50% reduction before IDS significantly influenced the PFS (HR = 0.29, p = 0.00008; HR = 0.23, p = 0.0024). The HE4 levels also correlated with the OS as follows: values below the median (HR = 1.88, p = 0.0087), normalization after chemotherapy (HR = 0.08, p = 0.0003), and 50% reduction before IDS (HR = 0.39, p = 0.0496).
The significant effect of the normalization of the HE4 marker after therapy and 50% reduction of HE4 levels before interval cytoreductive surgery on PFS and OS confirmed that HE4 might be an independent prognostic factor of treatment response. HE4 measurements performed during first-line treatment of ovarian cancer may have prognostic significance.
The aim of the study was to analyze the frequency and magnitude of association of 21 recurrent founder germline mutations in
,
,
,
, and
genes with ovarian cancer risk among unselected patients in ...Poland. We genotyped 21 recurrent germline mutations in
(9 mutations),
(4 mutations),
(3 mutations),
(2 mutations), and
(3 mutations) among 2270 Polish ovarian cancer patients and 1743 healthy controls, and assessed the odds ratios (OR) for developing ovarian cancer for each gene. Mutations were detected in 369 out of 2095 (17.6%) unselected ovarian cancer cases and 117 out of 1743 (6.7%) unaffected controls. The ovarian cancer risk was associated with mutations in
(OR = 40.79, 95% CI: 18.67-114.78;
= 0.29 × 10
), in
(OR = 25.98; 95% CI: 1.55-434.8;
= 0.001), in
(OR = 6.28; 95% CI 1.77-39.9;
= 0.02), and in
(OR 3.34; 95% CI: 1.06-14.68;
= 0.06). There was no association found for
We found that pathogenic mutations in
,
,
or
are responsible for 12.5% of unselected cases of ovarian cancer. We recommend that all women with ovarian cancer in Poland and first-degree female relatives should be tested for this panel of 18 mutations.
There are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian ...carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs.
The study group consisted of 102 patients with histologically confirmed BOT and 1743 healthy controls. In addition, 167 cases with ovarian cancer G1 were analyzed. The analyses included genotyping of 21 founder and recurrent mutations localized in 5 genes (BRCA1, BRCA2, PALB2, RAD51C, and CHEK2). The risk for developing BOT and low-grade ovarian cancer, as well as the association of tested mutations with survival, was estimated.
The CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03), at an earlier age at diagnosis and about 10% worse rate of a 10-year survival. Mutations in BRCA1 and PALB2 were associated with a high risk of ovarian cancer G1 (OR=8.53, p=0.005 and OR=7.03, p=0.03, respectively) and were related to worse all-cause survival for BRCA1 carriers (HR=4.73, 95%CI 1.45-15.43, p=0.01).
Results suggest that CHEK2 (c.470T>C) may possibly play a role in the pathogenesis of BOT, but due to the low number of BOT patients, obtained results should be considered as preliminary. Larger more in-depth studies are required.
MMP and TIMP play an important role in the degradation of extracellular matrix components which are essential for tumor growth, invasion and metastasis. Aim of this research was to assess MMP3 and ...TIMP3 as prognostic factors among patients with ovarian cancer.
It was found that high levels of output MMP3 correlated with shortened overall survival time of patients by 9.7 months. In addition, it has been shown that high concentrations of output MMP3 were significantly associated with a shorter disease free time in median concentrations implemented p = 0.0059. Statistically significant dependence has been shown between an average concentration of TIMP3 protein to the overall survival of patients. The higher output concentration of TIMP3, the longer patients' survival by 8.9 month. In addition, it was found that high TIMP3 concentrations output were associated with a significantly longer disease free duration at a median concentrations p = 0.007.
Preliminary research shows that output levels of MMP3 and TIMP3 proteins correlate with overall survival of patients. In some cases also time free of illness.
Cervical cancer is the third most common malignant neoplasm in women worldwide. HPV infection is the necessary factor for the cancer to develop. HPV DNA can be integrated into the genome of squamous ...epithelium and cause transcription of the viral oncoproteins and development of invasive cancer within 15-20 years. We assessed ICC co-expression of p16/Ki-67 proteins in smears collected from the uterine cervix and the association between p16/Ki-67 co-expression and cytologic and histologic results. Samples were collected from 93 women using liquid based cytology (LBC). Two microscopic slides were prepared: for Papanicolaou staining and ICC staining. Biopsy samples were collected from 43 women. Diagnosis of CIN 2+ was the endpoint of the study. p16/Ki-67 positive cells were found in women with: 1) a cytology result of ASC-US (3.59%), LSIL (2.22%), ASC-H (21.92%), HSIL (33.18%), SCC (72.22%) or NILM (3.44%); 2) a histopathologic result of CIN 1 (2.13%), CIN 2 (19.93%), CIN 3 (23.22%), SCC (69.72%) or normal histology (7.58%). p16/Ki-67 dual staining can increase the efficiency of screening methods and indicate women in whom further diagnostic procedures are required or those with extremely low risk of cancer. Sparing protocols will have a significant role in women of reproductive age.
An ERAS protocol provides the latest perioperative care principles, whose primary aim is to reduce complication rates, and therefore mortality. The aim of this study is to establish the progress of ...the ERAS pathway implementation in our gynaecology department.
This was a retrospective analysis of two sets of 100 consecutive medical records: patients treated before (PRE-ERAS) and after (ERAS) introduction of the ERAS protocol. All patients were comparable and all underwent major gynaecological surgery. Patients as well as medical and nursing staff were informed about the proposed preparation, surgical management and postoperative routine.
Patients were given supper and drank water during the night. Laparoscopic surgery was used in 44% and spinal anaesthesia was given for open surgery in 43 study patients. Use of drains was reduced only by 23%, bowel preparation by 15%. Intravenous fluid administration was reduced by 22%. Use of postoperative morphine was minimised to 12 patients. Postoperative nausea was managed with the regular use of anti-emetics. Anti-coagulation was given to 80% of the study group. Difficulties in the introduction of the ERAS protocol were due to refusal by some patients to mobilise and eat early postoperatively. Patients in the ERAS programme group were discharged earlier.Further information about the ERAS protocol in the media would facilitate patients' education among conservative society. In order to introduce new and innovative treatment methods, one has to take into account the cultural and ideological factors, especially when patient involvement is essential.
The most important prognostic factor in the ovarian cancer is optimal cytoreduction. The neoadjuvant chemotherapy, an only optional method of treatment in this case and is still the subject of ...debate. The object of this study was to evaluate the usefulness of markers: CA 125, HE4, YKL-40 and bcl-2 as well as cathepsin L in predicting optimal cytoreduction and response to chemotherapy.
Sera were secured preoperatively. The division into groups was performed retrospectively depending on the method of treatment (surgery vs neoadjuvant chemotherapy) as well as on response to chemotherapy (sensitive vs resistant vs refractory). Comparisons were made between groups, and the diagnostic usefulness of tested proteins was examined.
We found that statistically significant differences between primary operated patients and patients undergoing neoadjuvant chemotherapy were applicable only to the tumour markers (CA125 1206.79 vs 2432.38, p=0.000191; HE4 78.87 vs 602.45, p=0.000004; YKL-40 108.13 vs 203.96, p=0.003991). Cathepsin-L and Bcl-2 were statistically insignificant. The cut-off point values were determined for the CA 125 (345 mIU/ml), HE4 (218.43 pmol/L) and YKL-40 (140.9 ng/ml). The sensitivity, specificity, PPV and NPV were as follows: CA125 (83.3%; 75%; 80.6%; 78.3%), HE4 (86.6%; 91.3%; 92.9%; 84%) and YKL-40 (75%; 83.3%; 84%; 74.1%).
Among the tested proteins the HE4 marker appears to be helpful in forecasting of optimal cytoreduction and possibly also of the prediction of response to platinum analogues used in first-line treatment of ovarian cancer.
Ovarian cancer is characterised by the greatest mortality among all tumors of the reproductive tract.
This study included 246 patients which consisted of 136 women with ovarian cancer without genetic ...mutation and 110 women with benign ovarian cysts.
We created two mathematical logic models containing positive and negative risk factors of ovarian cancer such as: age at last menstruation cycle, patient age, OC, HRT, smoking, education status, and alcohol consumption. The calculated cut-off point for the first model was 0.5117. Classification determined on the basis of that cut-off point yielded 87.19% of correctly classified cases, of which 91.38% are “case” and 81.61% - „noncase”. For the second model the designated cut-off point was set at 0.5149 and the percentage of correctly classified patients was 88.12%, with 92.24% correctly rated as cancer patients and 82.56% of the cases rightly recognised as having no ovarian cancer.
Logit is a simple mathematical model that can be a useful tool for identification of patients with increased risk of ovarian cancer.
Breast and ovarian cancer penetrance in BRCA1 mutation carriers is estimated to be between 15% and 80% by age 70 years. At present, it is not possible to predict with any certainty who is most likely ...to develop disease or which age it will develop. Previous studies have tried to correlate the sites of BRCA1 mutations with disease risk; however, the results have not yielded any definitive association. An alternative explanation that could account for differences in the penetrance of BRCA1 mutations is the action of modifier genes. In this study, we have investigated the role of the RAD51_135_G>C polymorphism in breast and ovarian cancer case-control populations of Polish women who have been matched for BRCA1 mutation and year of birth. The results reveal that women who harbor the C allele have almost twice the reduction in breast and ovarian cancer risk compared with women who harbor only the G allele. These findings suggest that the effect of the RAD51 C allele is an important risk modifier for malignancies occurring on a background of BRCA1 mutations. In addition, we were able to show that the site of the BRCA1 mutation does not influence the effect of the RAD51 C allele, indicating that this polymorphism contributes to prevention of disease in BRCA1 carriers. In conclusion, the RAD51 C allele seems to protect against both breast and ovarian cancer in women harboring BRCA1 mutations.
The ovarian tumor microenvironment, ie, the peritoneal fluid, is an intriguing research subject. The goal of this study was to assess the behavior of selected cytokines and growth factors within the ...peritoneal fluid in pathologies associated with ascites and to assess the relationship between the levels of these substances and select prognostic factors of ovarian cancer.
A total of 74 patients were enrolled in the study, including 36 patients with ovarian cancer and 38 patients with benign gynecological conditions. Peritoneal fluid collected during surgical procedures was used to assess the levels of interleukin (IL)-6, IL-8, stem cell factor (SCF), dickkopf-1, growth differentiation factor-15 (GDF-15), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), osteoprotegerin (OPG), osteopontin, osteonectin, and human epididymis protein 4. The median levels of these factors were compared between the two groups, and the levels of selected factors were assessed in the ovarian cancer group with regard to the clinical stage of cancer, tumor differentiation, presence of peritoneal spread and positive peritoneal fluid cytology results. The diagnostic value of the analyzed proteins within the peritoneal fluid was also assessed.
Differences were observed between the patients with ovarian cancer and the patients with benign gynecological conditions associated with ascites with regard to the levels of IL-6, IL-8, GDF-15, SCF, osteopontin, osteonectin, and OPG. There were no differences in dickkopf-1, TRAIL, and human epididymis protein 4 levels between the two study groups. Cancer stage affected only the mean SCF and OPG levels, with lower SCF values and higher OPG values in advanced cancers compared to less-advanced cancers. Tumor differentiation was associated with significantly lower SCF values in the group of poorly differentiated tumors. A significant reduction in SCF values and a significant increase in OPG and IL-6 values were also observed within cancer cell-positive peritoneal fluid. Peritoneal spread was associated with higher levels of TRAIL, osteonectin, and IL-6 in ovarian cancer patients.
On the basis of the conducted studies, it appears that of the studied factors, GDF-15, SCF, and OPG deserve special attention in the context of future research on the tumor microenvironment. With regard to diagnostics, attention should be given primarily to GDF-15, IL-6, and osteonectin.
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