8 research outputs found
Effect of the 3q26-coding oncogene SEC62 as a potential prognostic marker in patients with ovarian neoplasia
With approximately 220,000 newly diagnosed cases per year, ovarian cancer is
among the most frequently occurring cancers among women and the second
leading cause of death from gynecological malignancies worldwide. About 70%
of these cancers are diagnosed in advanced stages (FIGO IIB–IV), with a 5-year
survival rate of 20–30%. Due to the poor prognosis of this disease, research has
focused on its pathogenesis and the identification of prognostic factors. One
possible approach for the identification of biological markers is the
identification of tumor entity-specific genetic “driver mutations”. One such
mutation is 3q26 amplification in the tumor driver SEC62, which has been
identified as relevant to the pathogenesis of ovarian cancer. This study was
conducted to investigate the role of SEC62 in ovarian malignancies. Patients
with ovarian neoplasias (borderline tumors of the ovary and ovarian cancer) who
were treated between January 2007 and April 2019 at the Department of
Gynecology and Obstetrics, Saarland University Hospital, were included in
this retrospective study. SEC62 expression in tumor tissue samples taken
during clinical treatment was assessed immunohistochemically, with the
calculation of immunoreactivity scores according to Remmele and Stegner,
Pathologe, 1987, 8, 138–140. Correlations of SEC62 expression with the TNM
stage, histological subtype, tumor entity, and oncological outcomes
(progression-free and overall survival) were examined. The sample
comprised 167 patients (123 with ovarian cancer and 44 with borderline
tumors of the ovary) with a median age of 60 (range, 15–87) years. At the
time of diagnosis, 77 (46%) cases were FIGO stage III. All tissue slides showed
SEC62 overexpression in tumor cells and no SEC62 expression in other cells.
Median immunoreactivity scores were 8 (range, 2–12) for ovarian cancer and 9
(range, 4–12) for borderline tumors of the ovary. Patients with borderline
tumors of the ovary as well as patients with ovarian cancer and an
immunoreactive score (IRS) ≤ 9 showed an improved overall survival compared to those presenting with an IRS score >9 (p = 0.03). SEC62 seems to
be a prognostic biomarker for the overall survival of patients with ovarian
malignancies
The 3q Oncogene SEC62 Predicts Response to Neoadjuvant Chemotherapy and Regulates Tumor Cell Migration in Triple Negative Breast Cancer
In the absence of targeted treatment options, neoadjuvant chemotherapy (NACT) is applied
widely for triple-negative breast cancer (TNBC). Response to NACT is an important parameter
predictive of oncological outcomes (progression-free and overall survival). An approach to the
evaluation of predictive markers enabling therapy individualization is the identification of tumor
driver genetic mutations. This study was conducted to investigate the role of SEC62, harbored at 3q26
and identified as a driver of breast cancer pathogenesis, in TNBC. We analyzed SEC62 expression
in The Cancer Genome Atlas database, and immunohistologically investigated SEC62 expression
in pre- and post-NACT tissue samples from 64 patients with TNBC treated at the Department of
Gynecology and Obstetrics/Saarland University Hospital/Homburg between January 2010 and
December 2018 and compared the effect of SEC62 on tumor cell migration and proliferation in
functional assays. SEC62 expression dynamics correlated positively with the response to NACT
(p ≤ 0.01) and oncological outcomes (p ≤ 0.01). SEC62 expression stimulated tumor cell migration
(p ≤ 0.01). The study findings indicate that SEC62 is overexpressed in TNBC and serves as a
predictive marker for the response to NACT, a prognostic marker for oncological outcomes, and a
migration-stimulating oncogene in TNBC
Influence of androgen levels on conception probability in patients undergoing fertility treatment: a retrospective cohort study
PurposePrimary and secondary sterility have become an issue of increasing importance due to demographic and social changes in society. Data regarding the association between female androgen levels and the probability of successful conception after fertility treatment are sparse and contradictive. This study was designed to assess this clinical question.MethodsIn this retrospective single-center cohort study concentrations of androgens androstenedione, dehydroepiandrosteronsulfat (DHEAS) and testosterone (ng/ml) were investigated in the serum of patients presenting for sterility at the department of reproductive medicine of Saarland University hospital Homburg between January 2015 and December 2017. Androgen levels were correlated with reproductive outcomes. Statistical analysis was performed with the aid of SPSS version 24. Significance for conception rates in dependence of androgen concentration was assessed using Kruskal-Wallis test (significance was estimated with p<0.05).ResultsThe laboratory values of a total of 301 patients were examined (64% primary, 36% secondary sterility). Median age at first visit at the fertility department was 32.7years (range 20-47years). 64 pregnancies were observed during the study period (conception rate 21.3%). 23 out of 301 patients (7.6%) suffered from hypoandrogenaemia, 248 (82.4%) had normal androgen levels and 30 (10%) showed hyperandrogenaemia (p=0.25). Regarding patients in whom fertility treatment was successful 3 (4.7%) showed hypoandrogenaemia, 54 (84.4%) were normoandrogenaemic and 7 (10.9%) had hyperandrogenaemia (p=0.40 Kruskal-Wallis test).ConclusionsWe found no association between female androgen levels and sterility and reproductive outcomes
Dkk1 as a Prognostic Marker for Neoadjuvant Chemotherapy Response in Breast Cancer Patients
Purpose: To investigate the role of Dkk1 as a predictor of response to NACT in BC patients.
Methods: This retrospective monocentric study included 145 women who had undergone NACT
followed by breast surgery. Dkk1 protein expression was assessed using immunohistochemistry
staining in core needle biopsies and mammary carcinoma specimens. Results: Dkk1 levels were
lower in treated BC tumours than in untreated tumours. The outcomes of 68 matched pre- and
post-therapy tissues showed that Dkk1 levels in mammary carcinoma tissues were significantly
predicted by levels in core needle biopsies and that Dkk1 expression was reduced in 83% of cases.
Smaller cT stage, positive Her2 expression, and decreased Dkk1-IRS in core needle biopsy tissues
were all independent predictors of regression grade (R4), according to Sinn. However, the percentage
of Dkk1 expression differences prior to and following NACT had no effect on PFS or OS. Conclusions:
In this study, we demonstrated for the first time that Dkk1 could be identified as an independent
predictor of NACT response in BC patients, particularly those with TNBC. Further research with a
multicentric expanded (pre-/post-therapy) sample set and better-defined populations in terms of
molecular subtypes, therapy modality, and long-term follow-up is recommended to obtain more
solid evidence