Sexual activity and quality of life in patients after treatment for breast and ovarian cancer.

OBJECTIVE: Sexual activity (SA) and functioning (SF) are important factors influencing quality of life (QoL). Anticancer treatment can cause or promote sexual dysfunctions. In this study we analyzed the SA, SF and QoL in patients after completion of treatment for breast cancer (BC) and ovarian cancer (OC). METHODS: In this retrospective multicenter study 396 BC patients and 93 OC patients aged between 18 and 70 years were surveyed at least 24 months after cancer diagnosis and compared to 60 healthy women. Data were collected through validated questionnaires (Sexual Activity Questionnaire, Female Sexual Function Index-d, EORTC Quality of Life Questionnaire-C30). RESULTS: 45.9% of BC patients and 56.5% of OC patients reported SA. SF and well-being of sexually active BC patients were not influenced by the type and radicality of surgery or the administration of chemotherapy. Patients who received antihormonal therapy at the time of evaluation showed a lower frequency of SA (p = 0.007), less satisfaction (p = 0.003) and more discomfort during SA (p = < 0.001) compared to healthy controls but no differences in experiencing orgasms, health status, QoL and global health status. In contrast, BC patients without antihormonal therapy showed only a higher discomfort score (p = 0.028) than healthy controls and estimated their health status and QoL significantly better than patients who received antihormonal therapy (p = 0006). In general, SA was associated with a better health status (p = 0.007), a better QoL (p = 0.004) and a better global health status (p = 0.004) in BC patients. Sexually active OC patients showed no significant differences in SF, QoL and health status compared to healthy controls. CONCLUSIONS: Compared to healthy controls BC patients showed limitations in SF with a lower SA rate and more discomfort. Antihormonal therapy was an important factor influencing SF and well-being. Breast and OC survivors reported good physical and psychical health without differences in QoL and health status compared to controls. This might be explained by a change of perspective on life difficulties and altered priorities through a life threatening disease.

Validity Parameters of the Human Papillomavirus Detection Test Hybrid Capture 2 With and Without Cytology After Laser Destruction and Large Loop Excision of the Transformation Zone Treatment of High-Grade Cervical Intraepithelial Neoplasia Lesions.

OBJECTIVE: The aim of this study was to calculate the validity parameters of the Digene Hybrid Capture 2 (HC2) high-risk human papillomavirus DNA test with and without cytology in the follow-up examinations after laser treatment of the transformation zone or large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia (CIN). METHODS: We performed a standardized follow-up examination in 113 postlaser and 153 post-LLETZ patients in our colposcopy clinic. Routine cytology, HC2 tests, and colposcopically-guided cervical biopsies were performed and sensitivity, specificity, and positive and negative predictive values were calculated using the histological cervical biopsy result as the criterion standard. RESULTS: After a median follow-up time of 25.5 months, the overall posttreatment recurrence/persistence rate of CIN 2 or higher (CIN 2+) was 24% after laser and 12.4% after Post-LLETZ treatment. Hybrid Capture 2 alone had a sensitivity/NPV of 70/88% in post-laser and 70/93% in post-LLETZ patients. Cytology alone had a sensitivity/NPV for CIN 2+ of 48/84% in post-laser and 58/91% in post-LLETZ patients. Combined testing of HC2 with cytology had a sensitivity/NPV of 81/92% in postlaser and 88/95% in post-LLETZ patients. DISCUSSION: In this test of cure study, combined testing of cytology with HC2 resulted in a high sensitivity and NPV. Hybrid Capture 2 and cytology-negative women may safely return to routine recall. Cytology alone is not an adequate follow-up strategy in postlaser patients.

Structured reporting ensures complete content and quick detection of essential data in pathology reports of oncological breast resection specimens.

There is increasing evidence that not only the way of data acquisition but also the design of data visualization (i.e., the format) has impact on the quality of pathology reports. Therefore, we investigated the correlation between the format of pathology reports and the amount as well as the detection time of transmitted data. All reports of oncological breast resection specimens referred to the Institute for Surgical Pathology, University Medical Center Freiburg, between 2003 and 2011 (n = 4181) were classified into descriptive reports (DR, n = 856), structured reports (SR, n = 2455), or template-based synoptic reports (TBSR, n = 870). The reports were screened regarding the content of nine organ-specific essential data. The amount of recorded essential data per report was summarized in an essential data score (EDS) and the format types were statistically compared regarding their EDS. Additionally, we measured the time a gynecologist needed to detect all nine essential data within a subset of reports and compared the format types regarding the detection times statistically. A full-score EDS of 9 was seen in 28.4 % of all reports, in 4 % of DRs, in 21.4 % of SRs, and in 72.3 % of TBSRs (p < 0.0001). Median EDS of DRs was 7, of SRs 8, and of TBSRs 9 (p < 0.0001). Data regarding tumor localization, tumor size, specific grading, angioinvasion, hormone receptor status, and additional findings were mentioned more frequently in TBSRs compared to other format type reports with a statistically highly significant difference (p < 0.0001). Mean data detection time decreased significantly from 26 to 20 and 14 s in DRs, SRs, and TBSRs, respectively. Our results clearly show that due to the use of TBSRs reporting of oncological breast resection specimens are improved regarding the content of essential data and the clarity of the data layout resulting in a rapid detection of essential data by clinicians.

MRI and FDG-PET/CT imaging in gynecological malignancies: the radiation oncology perspective.

MRI and FDG-PET imaging plays an important role in diagnosis, monitoring and follow-up of gynecological cancer. The goal of this paper was to summarize data of the literature about sensitivity and specificity of MRI and FDG-PET/CT for detection of primary tumor, lymph nodes invasion and metastases in cervix and endometrial cancer and to discuss their implication for radiation treatment planning and monitoring.

Hyperthermia-driven aberrations of secreted microRNAs in breast cancer in vitro.

PURPOSE: Expression profile alterations of nine breast cancer (BC)-associated secreted microRNAs (miRs) were determined under microenvironmental alterations occurring in tumour progression, metastasis or specific oncological treatment modalities. Thereto, the potential influence of the exogenic stimuli hypoxia, acidosis and hyperthermia was investigated in vitro. MATERIAL AND METHODS: Four established BC cell lines were applied as in vitro BC model systems. Quantitative analyses of secreted microRNA specimens were performed by RNA isolation from cell culture supernatant and subsequent real-time PCR in cells under physiological versus hypoxic, acidic or hyperthermia conditions. RESULTS: The in vitro application of exogenic stimuli hypoxia, extracellular acidosis and hyperthermia caused heterogeneous expression alterations for the investigated secreted miRNA phenotypes. The majority of relevant exogenic stimuli-dependent microRNA expression alterations were restricted to single events displaying distinct cell type and stimulus dependent correlations only. Most remarkably, hyperthermia triggered a uniform significant down-regulatory effect on the expression levels of the three secreted microRNAs miR-10b, miR-15b and miR-139, respectively. The marked decrease in miR-10b and miR-15b levels was detectable in all four, while miR-139 was found significantly reduced in three out of four BC cell lines. CONCLUSION: Hyperthermia-dependent down-regulatory influence on three distinct BC-related microRNAs in vitro generates translational aspects for clinical BC treatment, since the identified microRNAs miR-10b, miR-15b and miR-139 are known to have oncogenic as well as tumour suppressor functions in BC. However, an evaluation regarding the potential impact of microRNA-related hyperthermia-dependent alterations for innovative BC treatment approaches demands further analysis including in vivo data.

Feasibility of urinary microRNA detection in breast cancer patients and its potential as an innovative non-invasive biomarker.

BACKGROUND: Since recent studies revealed the feasibility to detect blood-based microRNAs (miRNAs, miRs) in breast cancer (BC) patients a new field has been opened for circulating miRNAs as potential biomarkers in BC. In this pilot study, we evaluated to our knowledge for the first time whether distinct pattern of urinary miRNAs might be also applicable as innovative biomarkers for BC detection. METHODS: Urinary miRNA expression levels of nine BC-related miRNAs (miR-21, miR-34a, miR-125b, miR-155, miR-195, miR-200b, miR-200c, miR-375, miR-451) from 24 untreated, primary BC patients and 24 healthy controls were quantified by realtime-PCR. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy. RESULTS: Significant differences were found in the expression of four BC-associated miRNAs quantified as median miRNA expression levels. Urinary miR-155 levels were significantly higher in BC patients compared to healthy controls (1.49vs.0.25; p < 0.001). In contrast, compared to healthy controls, BC patients exhibited significantly lower urinary expression levels of miR-21 (2.27vs.5.07; p < 0.001), miR-125b (0.71vs.1.62; p < 0.001), and miR-451 (0.02vs.0.59 p = 0.004), respectively. The ROC including all miRNAs as well as the group of the four significant deregulated miRNAs separated BC patients from healthy controls with a very high (area under the receiver operating characteristic curve [AUC] = 0.932) and high accuracy (AUC = 0.887), respectively. CONCLUSIONS: We were able to demonstrate for the first time the feasibility to detect distinct BC-dependent urinary miRNA profiles. The expression levels of four urinary miRNAs were specifically altered in our cohort of BC patients compared to healthy controls. This distinct pattern offers the possibility for a specific discrimination between healthy women and primary BC patients. This sustains the potential role of urinary miRNAs as non-invasive innovative urine-based biomarkers for BC detection.

Functional outcome after pelvic floor reconstructive surgery with or without concomitant hysterectomy.

PURPOSE: When counseling patients about surgical alternatives for pelvic organ prolapse (POP) repair, numerous things have to be considered. Uterine preservation vs. hysterectomy is one relevant issue. Hysterectomy has been traditionally performed for POP, but its benefit regarding outcome has never been proven. Furthermore, a growing number of women ask for uterine preservation. METHODS: In this retrospective cohort study, 384 patients who had undergone surgery for POP between 2000 and 2012 at Freiburg University Medical Center were included. Using a standardized questionnaire, further surgeries, urinary incontinence, recurrent POP, pessary use, and satisfaction with the surgical outcome were evaluated. The functional results after uterine preservation vs. concomitant hysterectomy were compared using t test. RESULTS: 196 (51.04%) women were available for follow-up and agreed to participate (n = 122 with hysterectomy, n = 72 with uterine-preserving surgery, respectively). After a mean follow-up time of 67 months, vaginal bulge symptoms and urinary incontinence did not differ between treatment groups. We observed higher success rates and satisfaction scores in the uterine-preserving group. Regarding satisfaction with surgery and whether the patients thought it had been successful, we observed a trend toward better results in the uterine-preserving group (mean satisfaction score: 8.45 ± 2.15 vs. 7.76 ± 2.91, range 0-10, p = 0.061; success: 91.4 vs. 81.7 %, p = 0.087). CONCLUSIONS: There was no difference with regard to functional outcome between patients with or without concomitant hysterectomy. Satisfaction with the operation was slightly higher after uterus preserving surgery. Therefore, uterine-preserving surgery is a valuable option unless there are contraindications.

Neoadjuvant chemotherapy in breast cancer significantly reduces number of yielded lymph nodes by axillary dissection.

BACKGROUND: Neoadjuvant chemotherapy (NC) is an established therapy in breast cancer, able to downstage positive axillary lymph nodes, but might hamper their detectibility. Even if clinical observations suggest lower lymph node yield (LNY) after NC, data are inconclusive and it is unclear whether NC dependent parameters influence detection rates by axillary lymph node dissection (ALND). METHODS: We analyzed retrospectively the LNY in 182 patients with ALND after NC and 351 patients with primary ALND. Impact of surgery or pathological examination and specific histomorphological alterations were evaluated. Outcome analyses regarding recurrence rates, disease free (DFS) and overall survival (OS) were performed. RESULTS: Axillary LNY was significantly lower in the NC in comparison to the primary surgery group (median 13 vs. 16; p < 0.0001). The likelihood of incomplete axillary staging was four times higher in the NC group (14.8% vs. 3.4%, p < 0.0001). Multivariate analyses excluded any influence by surgeon or pathologist. However, the chemotherapy dependent histological feature lymphoid depletion was an independent predictive factor for a lower LNY. Outcome analyses revealed no significant impact of the LNY on local and regional recurrence rates as well as DFS and OS, respectively. CONCLUSION: NC significantly reduces the LNY by ALND and has profound effects on the histomorphological appearance of lymph nodes. The current recommendations for a minimum removal of 10 lymph nodes by ALND are clearly compromised by the clinically already established concept of NC. The LNY of less than 10 by ALND after NC might not be indicative for an insufficient axillary staging.

Expression of tumor-promoting Cyr61 is regulated by hTRA2-ß1 and acidosis.

The matricellular protein Cysteine rich 61 (Cyr61) displays a remarkable diversity of multiple cellular functions involved in significant physiologic and pathologic processes. Cyr61 is known as an important player in tumor progression, promoting neovascularization and metastasis. Our prior investigations elucidated an oxygen-dependent Cyr61 alternative splicing process characterized by retention of its intron 3, regulating its biological function in a hypoxia-driven on/off switch mechanism. In this work, we identified extracellular acidosis as a potent inducer for altered Cyr61 alternative splicing pattern regulating Cyr61 expression. Intriguingly, splicing factor hTRA2-beta1 displayed an opposite effect on Cyr61 expression. Nuclear hTRA2-beta1 protein expression was found markedly reduced under acidic conditions. In keeping with these conclusions, we show that hTRA2-beta1 can specifically bind a 'GAAG' motif in Cyr61 exon 3 RNA, that the splicing factor displays acidosis-dependent protein localization in cellular compartments, and shRNA-mediated hTRA2-beta1 knock-down triggers the same effects on Cyr61 alternative splicing like acidosis or hypoxia. Our findings strongly support the hypothesis of a specific regulation of Cyr61 expression by hTRA2-beta1.

Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications.

BACKGROUND: Cancer-testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors. METHODS: The reactivity pattern of various mAbs (6C1, MA454, M3H67, 57B, E978, GAGE #26 and NY-BR-1 #5) were assessed by immunohistochemistry in a tissue micro array series of 210 randomly selected primary invasive breast cancers in order to study the diversity of different CTAs (e.g. MAGE-A, NY-ESO-1, GAGE) and NY-BR-1. These expression data were correlated to clinico-pathological parameters and outcome data including disease-free and overall survival. RESULTS: Expression of at least one CTA was detectable in the cytoplasm of tumor cells in 37.2% of the cases. NY-BR-1 expression was found in 46.6% of tumors, respectively. Overall, CTA expression seemed to be linked to adverse prognosis and M3H67 immunoreactivity specifically was significantly correlated to shorter overall and disease-free survival (p=0.000 and 0.024, respectively). CONCLUSIONS: Our findings suggest that M3H67 immunoreactivity could serve as potential prognostic marker in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define new targets for specific breast cancer therapies.

Alterations in expression pattern of splicing factors in epithelial ovarian cancer and its clinical impact.

OBJECTIVE: Alternative splicing represents an important nuclear mechanism in the posttranscriptional regulation of gene expression, which is frequently altered during tumorigenesis. Previously, we described marked changes in alternative splicing of the CD44 gene in ovarian and breast cancer as well as specific induction of distinct splicing factors during tumor development. The present study was focused on the expression profiles of different splicing factors, including classical serine-arginine (SR) proteins including ASF/SF2, hTra2ß1, hTra2α, and Y-box-binding protein (YB-1) in physiological and malignant epithelial ovarian tissue to evaluate their expression pattern with regard to tumor development and disease progression. MATERIALS AND METHODS: Expression levels of the different splicing factors were analyzed in physiological epithelial ovarian tissue samples, primary tumors, and metastatic samples of patients with a diagnosis of epithelial ovarian cancer using quantified reverse transcription polymerase chain reaction analysis. We examined more closely the splicing factor hTra2ß1 using Western blot analysis and immunohistochemistry. RESULTS: The analysis revealed a marked and specific induction of ASF/SF2, SRp20, hTra2ß1, and YB-1 in primary tumors as well as in their metastatic sites. However, in our patient cohort, no induction was seen for the other investigated splicing factors SRp55, SRp40, and hTra2α. CONCLUSIONS: Our results suggest a specific induction of distinct splicing factors in ovarian cancer tumorigenesis. The involvement of hTra2ß1, YB-1, SRp20, and ASF/SF2 in exon recognition and alternative splicing may be important for gene regulation of alternatively spliced genes like CD44 with potential functional consequences in this tumor type leading to progression and metastasis.

Quality of life and sexual functioning in endometrial cancer survivors.

OBJECTIVE: Recent evidence suggests equivalent efficacy in terms of local control for adjuvant vaginal brachytherapy (VBT) compared to external beam radiotherapy after surgery in patients with intermediate-high endometrial cancer. The objective of this study is to compare the quality of life (QoL) and sexual function of women with endometrial cancer that were treated with either surgery alone or surgery in combination with postoperative VBT. METHODS: Women were interviewed at least 5 years after initial treatment for endometrial cancer. QoL was evaluated by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the cervical cancer module, CX-24. Sexual function was evaluated by using the Female Sexual Function Index (FSFI). Eligible women had early stage disease, were currently disease-free, and had undergone surgery and adjuvant VBT, but neither external beam radiotherapy nor systemic treatment. This study group were then compared using univariate and multivariate analyses with an age-matched control group comprising of endometrial cancer patients without adjuvant VBT. RESULTS: Fifty-five patients (29 surgery plus VBT and 26 surgical controls without VBT) were included for analysis. With respect to QoL including, e.g., physical, role, emotional and social functioning and likewise in terms of sexual function univariate and multivariate analyses did not show significant differences between patients with VBT and the controls without VBT of any of the outcome measures. CONCLUSION: Adjuvant VBT after surgery does not seem to have a significant impact on quality of life and sexual function in endometrial cancer survivors.

Alternative splicing-related factor YT521: an independent prognostic factor in endometrial cancer.

BACKGROUND: YT521 is a splicing factor involved in alternative splicing regulation of several tumor biological important genes. Two messenger RNA (mRNA) isoforms due to YT521 exon6 alternative splicing exist, with so far unknown functional consequences. Further evidence exists for a direct influence of YT521 expression in tumorigenesis because its mRNA level is changed in tumors compared with physiological tissue. We investigated the potential impact of YT521 expression on tumor biological parameters in endometrial cancer (EC). METHODS: Real-time reverse transcription-polymerase chain reaction specifically detecting YT521 exon6-retention and exon6-skipping mRNA isoforms and immunohistochemistry were performed in a cohort of 130 EC tissue samples. RESULTS: Whereas YT521 exon6-retention mRNA was detectable in 86 (66.2%), the exon6-skipping isoform mRNA was expressed in only 8 (6.2%) of all EC samples. On the protein level, 104 (80%) of EC samples showed nuclear expression. The mRNA levels of exon6-skipping isoform were not correlated to any of the clinicopathological parameters of EC. In contrast, YT521 exon6-retention mRNA expression was positively correlated to metastasis (R = 0.196, P = 0.026) and inversely correlated to the protein expression levels (R = -0.205, P = 0.019). In univariate analyses, higher levels of YT521 exon6-retention mRNA were correlated to a poorer progression-free survival (P = 0.003), and this is confirmed by multivariate analyses (P = 0.019). The negative YT521 protein expression was correlated to poorer overall and disease-specific survival (P = 0.036 and P = 0.034), respectively, in univariate analyses. They are also confirmed by multivariate analyses (P = 0.021 and P = 0.010, respectively). CONCLUSIONS: We characterized for the first time in a clinical setting a new but rare exon6-skipping mRNA splicing isoform of YT521. Furthermore, we identified YT521 as a potential new independent prognostic factor for patients with EC: the lack of YT521 protein in tumor cells was highly predictive for a poor overall and disease-specific survival and independent from the histological subtypes.

Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial.

The combination therapy of doxorubicin and trastuzumab has been proven to be highly effective for metastatic breast cancer (MBC) patients with Her2/neu over-expressing tumors. However, this regimen is characterized by frequent cardiac toxicity, occurring in 27% of all treated patients and aggravating when the two substances are given concurrently. Pegylated liposomal doxorubicin (PLD) as a single agent reduces significantly cardiac toxicity and maintains efficacy compared to conventional doxorubicin. This prospective open labeled, multicenter phase II study assessed the potential cardiotoxicity and efficacy of PLD and trastuzumab as first and second line combination therapy in Her2/neu over-expressing MBC patients. Patients with Her2 over-expressing, measurable MBC with a baseline left ventricular ejection fraction (LVEF) > or =50% were treated with PLD 40 mg/m(2) every 4 weeks for 6 up to 9 cycles and weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg). Cardiotoxicity was defined as the appearance of clinical signs or symptoms of congestive heart failure in combination with a decrease in LVEF < or =44% or > or =10 units below the normal value of 50% in the obligatory, subsequently performed transthoracic echocardiography. Due to conflicting interests, the planned accrual goal of 30 patients was not reached. Finally 16 patients were enrolled. Ten patients presented with more than one metastatic site and six of them were in second-line therapy. The median LVEF in the study cohort was 66.1 +/- 8.68% at baseline, 62.7 +/- 5.11% after 6 cycles of therapy, 64.4 +/- 7.61% at the first follow up and did not change significantly (61.0 +/- 5.56% even at the 5th follow-up). Six out of 12 assessable patients (50.0%) demonstrated a clinical benefit and after a median follow-up of 15.4 months a median progression free survival of 9.67 and a median overall survival of 16.23 months. Non-cardiac side effects were mild with only 3 CTC grade 3 events of 247 treatment cycles (1.2%) and no grade 4 toxicities. The combination of PLD and trastuzumab in patients with Her2/neu over-expressing metastatic breast cancer is a safe, feasible and effective therapy. However, cardiac function should be monitored at close intervals. Due to the promising clinical response rates and mild toxicity profile in this prognostically unfavorable group, this combination therapy should be evaluated in larger studies.

Estimates of global research productivity in gynecologic oncology.

BACKGROUND: Societies worldwide invest considerably in research on oncological diseases of women. However, current literature lacks estimating this research production. We therefore evaluated quality and quantity of publications in gynecologic oncology. METHODS: Revisit of 6119 peer-reviewed articles published in Gynecologic Oncology and the International Journal of Gynecological Cancer from January 1996 to December 2006. Descriptive data on disease origin, main topic, and country of origin were collected and analyzed separately. Research productivity was adjusted to the national population and nominal gross domestic product per capita. RESULTS: Research production and international cooperative teamwork in the 2 main journals of gynecologic oncology increased within the 10 last years; 65.3% of all published articles dealt either with epithelial ovarian cancer, cervical cancer, or endometrial cancer. Endometrial cancer had the worst ratio number of publications to estimated national incidence (United States, 2007). The United States (41.15%) and Europe (29.72%) make up a striking 70.87% of the world's research production in the field of gynecologic oncology. However, the highest rate of increase shows in Turkey (22.5), the People's Republic of China (6.87), and South Korea (5.83). Adjusted to the national GDP per capita and population for the year 2006, research productivity seems best in Israel, Austria, and Turkey. CONCLUSION: Quantitatively, most publications come from the presumed countries. Within the limits of the methodology used in this study, adjustment to population and GDP per capita provides information on research output. The scientific output on endometrial cancer is comparably low.

Delivery through cervicovaginal fistula - literature review and case report.

Less than 10 deliveries via cervicovaginal fistula (CVF) with closed cervical os were reported so far. In the majority of cases, the patients had a history of induced abortions. The CVF was usually recognized due to postpartum hemorrhage. The facilitating role of prostaglandins used for labor induction was supposed. In all cases, the babies remained unaffected by the delivery route. We report a new case of a 37-year-old gravida 2, para 0, with a history of a paracervical tear following a first trimester abortion 11 years ago. The abortion and the laceration were not reported in the current obstetrical documentation. After labor induction using oral misoprostol in the 41 + 5 weeks of pregnancy, the patient delivered a healthy baby through a left-sided CVF, which imposed as bleeding paracervical laceration, 6 cm in diameter, extending to the vaginal fornix in the 3 o'clock position. The cervical os was only 1-1.5 cm dilated and imposed as an inelastic band ("squid ring") in the 9 o'clock position. The laceration was sutured under spinal anesthesia. The patient recovered quickly, and the postpartum hemoglobin drop was 2.8 g/dl. In conclusion, the possibility of CVF should be considered in women with a history of induced abortion.

Alpha-folate receptor expression in epithelial ovarian carcinoma and non-neoplastic ovarian tissue.

BACKGROUND: The goal of this study was to evaluate the expression pattern and intracellular localization of alpha-folate receptor (alpha-FR) protein in human ovarian carcinoma compared with non-neoplastic ovarian tissue. MATERIALS AND METHODS: Using immunohistochemistry (IHC), alpha-FR protein expression was analyzed in specimens of 104 human ovarian carcinomas and 30 non-neoplastic ovaries. RESULTS: In 97% of the ovarian carcinomas, clear alpha-FR protein expression was detected (14% weak, 39% moderate, 44% strong). In the non-neoplastic ovaries, no (37%) or only weak (63%) expression was observed (p<0.0001). The tumor cells were characterized by a diffuse and homogeneous staining pattern. In tumor and non-tumor tissue, alpha-FR protein was detected predominantly in the cellular cytoplasm. In 41% of the ovarian carcinomas, cytoplasmic expression was localized towards the outer boarders of the invasive tumor cells and 30% exhibited additional nuclear alpha-FR protein expression. CONCLUSION: Compared with nonneoplastic ovaries, alpha-FR protein is overexpressed in human ovarian carcinoma tissue.

Predictive value of Aurora-A/STK15 expression for late stage epithelial ovarian cancer patients treated by adjuvant chemotherapy.

PURPOSE: To investigate the expression and regulation of the centrosomal kinase Aurora-A/STK15 (AURKA) in epithelial ovarian cancers and to determine the prognostic and predictive value of this marker for patients with late stage epithelial ovarian cancer treated by distinct adjuvant chemotherapies. EXPERIMENTAL DESIGN: Archival resection specimens of epithelial ovarian cancers (n=115) and nonneoplastic ovaries (n=28) were analyzed for AURKA mRNA and protein expression by microdissection and quantitative reverse transcriptase-PCR and immunohistochemistry. AURKA DNA copy numbers were measured by fluorescence in situ hybridization in 37 cases. Statistical evaluation was done with respect to clinicopathologic variables, disease-free survival, and overall survival. RESULTS: AURKA mRNA expression was significantly elevated in cancers (P<0.001) and correlated with AURKA protein expression (P=0.0134). Overexpression of AURKA protein was detected in 68 of 107 (63.5%) cases and was linked with increased AURKA DNA copy numbers (P=0.0141) and centromere 20 aneusomy (P=0.0137). Moreover, AURKA overexpression was associated with improved overall survival in optimal debulked patients receiving taxol/carboplatin therapy (n=43, P=0.018). Finally, in an exploratory approach, patients receiving non-taxane-based therapy, AURKA overexpression was predictive for worse overall survival (n=30, P=0.049). CONCLUSIONS: AURKA overexpression is seen in the majority of late stage epithelial ovarian cancers, most likely due to increased AURKA DNA copy numbers and/or chromosome 20 aneusomy. Importantly, AURKA overexpression may differentially affect taxane and non-taxane-based adjuvant therapy responses. The study sheds new light on AURKA expression and regulation in epithelial cancers in vivo and specifically shows its value as a clinically relevant marker and as a potential therapeutic target per se.

Transketolase protein TKTL1 overexpression: A potential biomarker and therapeutic target in breast cancer.

Malignant tumors degrade glucose to lactate even in the presence of oxygen via the pentose phosphate pathway (ppp). The non-oxidative part of the ppp is controlled by thiamine-dependant transketolase enzyme reactions. Overexpression of the transketolase-like-1-gene (TKTL1) in urothelial and colorectal cancer is associated with poor patient outcome. We analyzed the expression of the TKTL1 protein in a retrospective institution-based patient cohort with invasive breast cancer by immunohistochemical analysis of 124 paraffin-embedded breast cancer tissues. Our study revealed TKTL1 expression in 86% of breast cancer specimens with 45% showing high expression levels. In contrast, only 29% of corresponding non-neoplastic breast tissues were TKTL1 immunopositive, including 9% with high expression levels. High expression levels of TKTL1 correlated significantly to Her2/neu overexpression (p=0.015). However, TKTL1 expression failed to reach statistical significance for other common prognostic parameters. In contrast to recent data for e.g. colorectal cancer TKTL1 overexpression did not correlate to patient outcome and survival. However, in the context of novel insights into TKTL1-related tumor metabolism and the high proportion of TKTL1 overexpressing breast cancers, this enzyme represents a potential candidate for targeted inhibition of tumor growth in this tumor entity.