Ovarian, endometrial, and cervical cancers are three of the most common malignancies of the female reproductive organs. CA 125, historically the most reliable serum marker for ovarian cancer, is elevated in 50% of early-stage ovarian tumors. For endometrial cancers, there are no established serum markers. SCC, which is the best studied serum marker for squamous cell carcinomas, has been unreliable; SCC is elevated in cervical squamous cell carcinomas ranging from 28–85% of the time. Recent proteomics-based analyses show great promise for the discovery of new and more useful biomarkers. In this review, we will discuss the currently utilized serum tumor markers for gynecologic cancers and the novel biomarkers that are now under investigation.
ovarian; endometrial; cervical; cancer; serum; tumor marker; CA 125; SCC; proteomics; biomarkers
UGF is a small peptide present in the urines and tissues of patients with gynecologic cancers. Published research (which, at present, mainly comes from our laboratory) on the general application of UGF as a tumor marker, and on its use in the diagnosis of ovarian cancer, is reviewed, and new studies on its use, alone and with CA125, in the management of patients with ovarian cancer, are presented. In 234 healthy women, 89 with benign disease, and 79 with ovarian cancer, UGF levels were above 3 fmol/ml (low cut-off) in 12 percent, 7 percent, and 82 percent, respectively, and above 8 fmol/ml (high cut-off) in 1.7 percent, less than 1.1 percent, and 59 percent, respectively. Similarly, 11 percent, 14 percent, and 70 percent, respectively, had CA125 levels above 35 U/ml (low cut-off), and less than 1.9 percent, 1.2 percent, and 49 percent had levels above a 200 U/ml (high cut-off). Ideally, the higher UGF and CA125 cut-offs should be used for diagnostic applications, like differentiation of a benign from a malignant pelvic mass (false-positive rate: UGF, less than 1.1 percent; CA125, 1.2 percent), but raising the cut-offs diminishes sensitivities for malignancy (UGF, 59 percent; CA125, 49 percent). The populations detected by the two markers only partially overlap, however, so that, together, UGF or CA125 can identify 75 percent of malignant pelvic masses. Levels of UGF (cut-off, greater than 3 fmol/ml) and CA125 (35 U/ml) were also monitored in 30 women undergoing therapy for ovarian cancer. Clinical observations were reflected at each clinic visit by UGF alone in 67 percent, by CA125 alone in 57 percent, and by UGF and CA125 together in 87 percent of cases. While separately UGF and CA125 levels predicted 71 percent and 57 percent, together they forecast 86 percent of recurrent cancers prior to clinical manifestations. UGF and CA125 should be used together in the detection and management of ovarian cancers.
Ovarian cancer rarely complicates pregnancy. Usually these malignancies consist of germ cell tumors. Preserving maternal safety along with favorable neonatal outcome is a subject of debate in the management of ovarian cancer during pregnancy. In this report, the authors describe a 25-year-old primigravid woman who was diagnosed to with an ovarian immature teratoma which was diagnosed at 13th weeks of pregnancy during a routine sonography. She underwent oophorectomy at week 21 of her gestation. Then she received three cycles of BEP regimen (bleomycin, etoposide, and cisplatin) during her pregnancy until week 37 of gestation. At 36 weeks she delivered a male baby with mild glandular hypospadia who was otherwise normal. Management of immature teratoma after the first trimester of pregnancy is similar to non-pregnant patients and is safe for both the mother and the fetus.
Germ cell tumor; Ovary; Pregnancy; Chemotherapy
Ovarian cancer is the most lethal gynecologic malignancy, with the majority of patients dying within 5 years of diagnosis. This poor survival of patients diagnosed with this malignancy is attributed to diagnosis at advanced stage, when the tumor has metastasized, and to chemotherapy resistance, either primary or developing along tumor progression. However, ovarian carcinomas, constituting the vast majority of ovarian cancers, additionally have unique biology, one aspect of which is the ability to co-express epithelial and mesenchymal determinants. epithelial–mesenchymal transition (EMT), a physiological process by which mesenchymal cells are formed and migrate to target organs during embryogenesis, is involved in cancer cell invasion and metastasis. However, these changes do not fully occur in ovarian carcinoma, and are even reversed in tumor cells present in malignant peritoneal and pleural effusions. This review summarizes current knowledge in this area, including the characteristics of EMT related to adhesion, transcriptional regulation and chemoresistance, and their clinical relevance, as well as the recently observed regulation of EMT by microRNA.
ovarian carcinoma; epithelial–mesenchymal transition; mesenchymal–epithelial transition; metastasis; tumor progression; chemotherapy; prognosis
Gynecologic malignancy during pregnancy is a stressful problem. For the diagnosis and treatment of malignancy during pregnancy, a multidisciplinary approach is needed. Patients should be advised about the benefits and risk of treatment. When selecting a treatment for malignancy during pregnancy, the physiologic changes that occur with the pregnancy should be considered. Various diagnostic procedures that do not harm the fetus can be used. Laparoscopic surgery or laparotomy may be safely performed. The staging approach and treatment should be standard. Systemic chemotherapy during the first trimester should be delayed if possible. Radiation therapy should preferably start postpartum. Although delivery should be delayed preferably until after 35 weeks of gestation, termination of pregnancy may be considered when immediate treatment is required. Subsequent pregnancies do not increase the risk of malignancy recurrence.
Chemotherapy; Gynecologic cancer; Pregnancy; Radiotherapy
Although occurrence of cancer during pregnancy is rare, it leads to high morbidity and mortality in both mother and fetus. Recent trends in prolongation of child-bearing age have made cancer-associated pregnancies more frequent than past. As yet there are few documents concerning cancer and its related treatment outcomes during pregnancy. This study aimed at describing clinical characteristics of pregnant women with cancer in the Shahid Sadoughi hospital in Yazd, Iran.
Materials and methods:
Case series were reviewed retrospectively, which included 19 pregnant women diagnosed with cancer in Shahid Sadoughi hospital from 2002 to 2012. Data collected comprised demographics, pregnancy characteristics and outcomes, type of cancer, clinical stage, treatment and oncological.
From 17 pregnant women with cancer, 4 women had gynecologic cancers and 13 had non-gynecologic cancers. The Following tumors were observed: breast , acute myeloblastic leukemia , uterine cervix carcinoma , ovary , chronic myelogenous leukemia , lymphoma , papillary carcinoma of thyroid , and pseudopapillary carcinoma of pancreas . The mean age of patients was 30.6 years, and the mean gestational age at diagnosis was 21.1 weeks. Surgical treatment was performed in 3 patients, 6 patients were treated by chemotherapy, and in 3 by both.
Although cancer during pregnancy is uncommon, it is considered an important problem due to unsuitable maternal and fetal outcomes and lack of standard management guidelines. Our cases represent examples of feasible or justifiable managements for them.
cancer; pregnancy; outcome; Yazd; diagnosis; treatment; management
Pregnancy-associated breast cancer (PABC) is defined as breast cancer occurring anytime during gestation, lactation or within one year after delivery. The optimal management of pregnant women with breast cancer is challenging and not well established; the main concern is the effect of the drugs on the developing fetus and long-term complications after in utero exposure to anti-cancer drugs. Surgical resection is the mainstay of treatment for early breast cancer diagnosed during pregnancy. Modified radical mastectomy is standard of care in first trimester, whereas breast-conserving surgery (lumpectomy with lymph node dissection) can be performed preferably in the second and third trimester. Of note, breast-conserving surgery is not contraindicated per se during the first trimester, but owing to the potential impact of delaying radiotherapy. Radiation therapy is not favored during pregnancy. Moreover, tamoxifen is contraindicated during pregnancy; the agent has been associated with birth defects in up to 20% of exposures. Chemotherapy is generally contraindicated during the first trimester because of the possible damage to organogenesis. Anthracyclines-based regimens are the most widely used is breast cancer treatment and were been shown to be associated with favourable safety profile when administered during pregnancy. As for taxanes, more limited data is available. The use of trastuzumab is contraindicated during pregnancy, given the apparent risk of oligo- and/or anhydramnios as well as the unknown long-term sequelae on the fetus. It is obvious that, diagnosis of breast cancer during pregnancy adds complexity to cancer treatment recommendations. In all cases, a multidisciplinary therapeutic approach among obstetricians, gynaecologists, surgical oncologists, radiation oncologists, medical oncologists, pediatricians and hematologists is clearly warranted.
Breast cancer; pregnancy; controversies; chemotherapy
Uncertainties persist about management and prognosis of mammary cancers that occur during and after pregnancy and during lactation. Pathological features of mammary cancers occurring during pregnancy are the same as those in non-pregnant women and survival rates are comparable. Management should be the same as in non-pregnant patients. Termination of pregnancy does not improve survival but it should be advised if the prognosis is poor. Mastectomy apparently presents little danger to the fetus, though treatment such as chemotherapy and irradiation should be avoided. Women who have received treatment for mammary cancer need not be advised against subsequent pregnancy. Routine ovarian radiation in non-pregnant premenopausal women is not generally to be recommended, since it does not prolong survival and would deprive some of the chance of further pregnancy. In lactating women who develop mammary cancers survival is apparently not adversely affected. Lactation should be suppressed initially and followed by mastectomy. Regimens of immunotherapy, chemotherapy, or radiotherapy may then be begun. Until results of current trials of combined treatments of mammary cancers associated with pregnancy are available, management should be neither aggressive nor tentative. It should be based on a well-balanced concept of applying all available treatments, as in non-pregnant patients.
For women who suffer from systemic lupus erythematosus (SLE), pregnancy can be a concern, placing the mother and fetus at risk. Our objectives were to assess the risk of adverse pregnancy outcome, disease flares, fertility rate, and co-morbidities in SLE women compared to healthy controls. We also systematically reviewed the literature available on pregnancy outcome in SLE to compare our results to other published data. Our hypothesis was that pregnancy outcome in SLE is improving over time.
A case-control study comparing self-report of the above-mentioned parameters in SLE (N=108) vs healthy controls or patients with non-inflammatory musculoskeletal (MSK) disorders (N=134) was performed. Data were collected using a self-administered questionnaire. Proportions, means and odds ratios were calculated. We searched and quantified the literature on pregnancy outcome, lupus reactivation and fertility rate. Data were summarized and presented in mean % ± SEM and median % with interquartile range (IQR).
Gynecological history, fertility rate and age at first pregnancy in SLE patients were comparable to controls. Eighteen percent of SLE patients reported a flare and 18% reported an improvement of symptoms during pregnancy. Twenty-four percent of lupus patients had at least one preterm delivery vs 5% in controls (OR =8.32, p = 0.0008), however other pregnancy outcomes (miscarriage, therapeutic abortion, stillbirth and neonatal death rate) did not differ between the groups. Thyroid problems were reported to be more likely in SLE patients (p = 0.02), but the prevalence of other co-morbidities was similar to controls. A literature review demonstrated that fertility was not affected in SLE patients. Lupus reactivations are common during pregnancy (36.5% ± SEM 3.3%). Most agreed that SLE pregnancies had more fetal loss (19.5% ± SEM 1.6%) and preterm births (25.5% ± SEM 2.2%) when compared to the general population. Over time, the rate of SLE peripartum flares has improved (p = 0.002) and the proportion of pregnancies resulting in live birth has increased (p = 0.024). The frequency of fetal death has not significantly changed. Our findings from the case-control study were, in general, consistent with the literature including the frequency of fetal death, neonatal death, live births and pregnancy rate.
Prematurity (25.5% ± SEM 2.2%) and fetal death (19.5% ± SEM 1.6%) in SLE pregnancy are still a concern. However, new strategies with respect to pregnancy timing and multidisciplinary care have improved maternal and fetal outcome in SLE.
Pregnancy outcome; systemic lupus erythematosus (SLE); case-control.
During the past decades, the expansion of molecular biology has had a pivotal role in understanding the basis of cancer development and progression. In addition, real advances have been made in the application of DNA recombinant technology to cancer therapy and patient management. In gynecologic oncologic fields, there are also many investigations to explore the basic pathogenesis of gynecologic cancer, such as cervical cancer, ovarian cancer, and endometrial cancer. It is now known that specific types of human papilloma virus (HPV) are the principal etiologic agents for both cervical cancer and its precursors. However, the various kinds of alterations in oncogenes and tumor suppressor genes may play additional roles in carcinogenesis of cervical cancer. Although ovarian carcinoma is the most frequent cause of death from gynecologic malignancies, the histogenesis and biological characteristics of these tumors are not well understood. During the last several years, many key observations have been made concerning the genetic alterations associated with ovarian cancer. Recent researches including some dominant oncogenes and tumor suppressor gene mutations common to these malignancies are providing bases to elucidate the mechanisms underlying this cancer. The most important basis of endometrial cancer is that K-ras and p53 mutations are also frequently observed.
This Commentary addresses issues related to exposures to teratogens and makes the case for increased research into the safety of medications during pregnancy for mothers and fetuses. Not only are medications commonly used during pregnancy, but evidence points to an increasing prevalence and number of drug exposures experienced by the embryo or fetus, particularly during the critical first trimester of pregnancy. Although the first trimester represents a particularly vulnerable period of organogenesis, exposures during other gestational time periods may also be associated with deleterious outcomes. In addition to the changing (and in many cases unknown) risks to a developing fetus, other challenges to studying medication exposures and their effects during pregnancy include the dramatic changes in physiology that occur in pregnant women and the ethical dilemmas posed by including this vulnerable population in randomized controlled trials of safety and efficacy. However, without adequate knowledge of the pharmacokinetics, pharmacodynamics, efficacy, and safety of medication use in pregnancy, women may be under-dosed to minimize exposure or not treated at all, resulting in inadequate treatment and potential harm to the mother and her baby. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is undertaking studies on medications and teratogenic exposures during pregnancy, including alcohol, maternal diabetes, oral hypoglycemic agents, and antiviral medications, through several of its research networks. Although this is a start, there is a critical need for further research on medications used during pregnancy, especially their effects on both the mother and her developing child.
medication; exposure; pregnancy; teratogen; research
Although the incidence of ovarian cancer is low (i.e., less than 5% in European countries), it is the most lethal gynecologic malignancy and typically has a poor prognosis. To ensure optimal survival, it is important to diagnose this condition when the pathology is confined to the ovary. However, this is difficult to achieve because the first specific symptoms appear only during advanced disease stages. To date, the biomarker mainly used for the diagnosis and prognosis of ovarian cancer is CA125; however, this marker has a low sensitivity and specificity and is associated with several other physiological and pathological conditions. No other serum ovarian cancer markers appear to be able to replace or complement CA125, and the current challenge is therefore to identify novel markers for the early diagnosis of this disease. For this purpose, studies have focused on the microvesicles (MVs) released from tumor cells. MVs may represent an ideal biomarker because they can be easily isolated from blood, and they have particular features (mainly regarding microRNA profiles) that strongly correlate with ovarian cancer stage and may be effective for early diagnosis.
The aim of this study was to analyze and describe cases of ovarian cancer in pregnant women treated at our center and to review the literature concerned, and to discuss the rationale for therapy.
Twenty-Three patients of ovarian malignancies during pregnancy were treated at Vali- Asr Hospital between 1991 and 2002. Data on treatment and follow-up were evaluated.
The incidence of ovarian carcinoma associated with pregnancy in our series was 0.083/1000 deliveries. Eleven (47.8%) were found with ovarian malignant germ cell tumors, five (21.7%) with low malignant potential tumors, four (17.4%) with invasive epithelial tumors, and three (13%) with sex cord stromal tumors. Seventeen (73.9%) of the patients were diagnosed in stage I and had complete remission. Five of the six in advanced stage died. The mean follow-up was 36.3 months. The prognosis was significantly related with stage and histological type (P < 0.05). Sixteen healthy live babies were recorded in this group, and two premature newborn died of respiratory distress syndrome. Chemotherapy was administered to 44% of the patients, in two cases during pregnancy. Overall survival at 5 years was 61%. In most of case conservative surgical treatment could be performed with adequate staging and debulking.
Early finding of ascitis by ultrasound and persistent large ovarian mass during pregnancy may be related to malignancy and advanced stage. Pregnant women in advanced stage of ovarian cancer seem to have poor prognosis.
The management of ovarian cancer during pregnancy is still a big challenge, mostly due to the reciprocal impacts between cancer and pregnancy. The objective of this article is to present a rare case of maternal ovarian adenocarcinoma and review published similar cases about this clinical condition.
Materials and methods
Here we report a rare case of maternal ovarian adenocarcinoma detected during gestational week 6, with good pregnancy outcome treated with conservative surgery.
Results and discussion
A case of maternal ovarian adenocarcinoma (stage I) was detected in week 6 of pregnancy receiving conservative surgery without chemotherapy. In week 39 of pregnancy, due to relapse of the cancer, the patient underwent excision of the isolated tumor, and gave birth to a healthy baby through cesarian section. After that, the patient received cytoreductive surgery associated with six chemotherapy. The patient was finally diagnosed as epithelial ovarian cancer stage IIIC, and had survived more than 5 years without relapse. The successful experience from this case suggested that pregnancy complicated with early ovarian cancer receiving conservative surgery could continue to pregnancy and the effect of cesarian section followed with cytoreductive surgery associated with six chemotherapy at full term was still satisfied.
Pregnancy; Ovarian cancer; Cytoreductive surgery; Chemotherapy
The objective of this study was to ascertain the evidence on ovarian cancer during pregnancy and compile recommendations derived from this information. This was a retrospective study, based on clinical histories from patients diagnosed and treated at 4 independent hospitals for ovarian cancer during pregnancy, between 1992 and 2009. The median age at diagnosis was 30 years (range, 24–41). Out of 10 cases of ovarian cancer, 2 patients showed either bleeding or abdominal pain, while 8 patients were asymptomatic. All 10 cases were diagnosed via ultrasound, and the masses were detected in the first trimester in 7 patients and in the second trimester in 2 patients. Of the diagnosed tumors, 8 cases were epithelial tumors including 6 adenocarcinomas and 2 borderline tumors, and 2 germ cell tumors. The primary ovarian malignancies were at stage I of the disease. Unilateral salpingo-oophorectomy was performed in 9 patients and cystectomy was performed in one patient. Chemotherapy was administered to 4 patients, in 1 case during pregnancy. Neonatal outcome analysis showed a full- or pre-term delivery in 6 cases, abortion in 1 case and therapeutic termination in 3 cases. The majority of cases of ovarian cancer in pregnancy were incidentally detected by ultrasound at an early stage, resulting in good prognosis for the mother and the neonate.
ovarian cancer; pregnancy; pelvic ultrasonography; pathology
The use of pharmacological agents in pregnant females poses a major clinical challenge due to the marked physiological changes that may modify the pharmacokinetics of drugs and to the potential effects on the fetus. The purpose of this paper is to review briefly our knowledge on the use of antibacterial drugs during pregnancy and to provide information for the judicious selection of an antimicrobial treatment for use in pregnant bitches and queens. The risk to the fetus is a result of the ability of a drug to reach the fetal circulation and to produce toxic effects. The placenta functions as a barrier that protects the fetus due to the presence of transporters and metabolising enzymes; however, during pregnancy, the presence and activity of both enzymes and transporters may change. Antimicrobial agents that have been shown to be safe for use during pregnancy include betalactams, macrolides, and lincosamides. Pharmacotherapy during pregnancy in all species may affect adversely the developing fetus; therefore, it should be avoided when possible.
To evaluate the prognostic significance of histologic grade on survival of ovarian serous cancer in Denmark during nearly 30 years.
Using the nationwide Danish Pathology Data Bank, we evaluated 4,317 women with ovarian serous carcinoma in 1978–2006. All pathology reports were scrutinized and tumors classified as either low-grade serous carcinomas (LGSC) or high-grade serous carcinomas (HGSC). Tumors in which the original pathology reports were described as well-differentiated were classified as LGSC, and those that were described as moderately or poorly differentiated were classified as HGSC. We obtained histologic slides from the pathology departments for women with a diagnosis of well-differentiated serous carcinoma during 1997–2006, which were then reviewed by expert gynecologic pathologists. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression analysis with follow-up through June 2009.
Women with HGSC had a significantly increased risk of dying (HR=1.9; 95% CI: 1.6–2.3) compared with women with LGSC while adjusting for age and stage. Expert review of 171 women originally classified as well-differentiated in 1997–2006 were interpreted as LGSC in 30% of cases, whereas 12% were interpreted as HGSC and 50% as serous borderline ovarian tumors (SBT). Compared with women with confirmed LGSC, women with SBT at review had a significantly lower risk of dying (HR=0.5; 95% CI: 0.22–0.99), and women with HGSC at review had a non-significantly increased risk of dying (HR=1.6; 95% CI: 0.7–3.4).
A binary grading system is a significant predictor of survival for ovarian serous carcinoma.
Ovarian serous carcinoma; binary grading system; overall survival; population-based; registry-based; expert gynecologic pathology slide review
Human epididymis protein 4 (HE4) is a novel and specific biomarker for ovarian cancer. The aim of this study is to evaluate a new tumor marker, HE4, in comparison with CA125 in diagnosis of epithelial ovarian cancer (EOC) and benign gynecological diseases.
CA125 and HE4 serum levels were determined in 30 patients with epithelial ovarian cancer (21 serous, 6 endometrioid and 3 mucinous tumors), 20 patients with benign gynecological diseases (8 patients with ovarian cyst, 5 patients with endometriosis, 4 patients with fibroid and 3 patients with pelvic inflammatory disease) and 20 healthy women. CA125 and HE4 cut-offs were 35 U/ml and 150 pmol/l, respectively.
Serum HE4 and CA125 concentrations were significantly higher in the ovarian cancer patients compared with those seen in patients with benign disease or in the healthy controls (p = 0.001 and p < 0.001 respectively). In the receiver operating characteristic analysis (ROC), the area under the curve (AUC) values for HE4 was 0.96 (95% confidence interval, 0.9-1.0) and CA125 was 0.82 (95% confidence interval, 0.7-0.94). Compared to CA125, HE4 had higher sensitivity (90% vs. 83.3%), specificity (95% vs. 85%), PPV (93.1% vs. 80.7%) and NPV (92.7% vs. 87.2%), the combination of HE4 + CA125 the sensitivity and PPV reached 96.7% and 97% respectively.
Measuring serum HE4 concentrations along with CA125 concentrations may provide higher accuracy for detecting epithelial ovarian cancer.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060413168685759
Human epididymis protein 4; HE4; Carbohydrate antigen125; CA125; Epithelial; Ovarian cancer; EOC
Pregnancy causes anatomic and physiologic changes in the gastrointestinal tract. Pregnant women with intestinal disease such as Crohn disease or ulcerative colitis pose a management challenge in clinical diagnosis, radiologic evaluation, and treatment secondary to potential risk to the fetus. Heightened physician awareness on possible etiologies such as appendicitis, diverticulitis, and rarely colorectal cancer is required for rapid diagnosis and treatment to improve maternal/fetal outcome. A multidisciplinary approach to evaluation is a necessity because radiologic procedures and treatment medications commonly used in nonpregnant patients may have a potential harmful effect on the fetus. The authors review several gastrointestinal conditions encountered during pregnancy and address presentation, diagnosis, and treatment of each condition.
Gastrointestinal; pregnancy; constipation; inflammatory bowel disease
Tumor necrosis factor-α inhibitors (anti-TNFs) are effective in the treatment of inflammatory bowel disease (IBD) recalcitrant to conventional medical therapy. As the peak incidence of IBD overlaps with the prime reproductive years, it is crucial to establish pharmacologic regimens for women of childbearing age that achieve effective disease control without posing significant fetal harm. A systematic literature review was performed to identify all human studies with birth outcomes data after maternal exposure to infliximab, adalimumab, or certolizumab pegol within 3 mo of conception or during any trimester of pregnancy. Live births, spontaneous abortions or stillbirths, preterm or premature births, low birth weight or small for gestational age infants, and congenital abnormalities were recorded. Fifty selected references identified 472 pregnancy exposures. The subsequent review includes general information regarding anti-TNF therapy in pregnancy followed by a summary of our findings. The benefits of biologic modalities in optimizing disease control during pregnancy must be weighed against the potential toxicity of drug exposure on the developing fetus. Although promising overall, there is insufficient evidence to prove absolute safety for use of anti-TNFs during pregnancy given the limitations of available data and lack of controlled trials.
Tumor necrosis factor-α inhibitors; Pregnancy; Congenital abnormalities; Safety; Infliximab; Adalimumab; Certolizumab
Lynch syndrome (LS) is an autosomal dominant familial cancer risk syndrome that occurs due to a germline mutation in one of several mismatch repair genes and is associated with an increased risk of colorectal, endometrial, and ovarian cancer. The risk of endometrial cancer equals or exceeds that of colorectal cancer in women with LS. The diagnosis of gynecologic cancer precedes that of colorectal cancer in over half of women with metachronous gynecologic and colon cancers, making gynecologic cancer a “sentinel cancer” for LS. There are no studies addressing the effectiveness or safety of chemoprevention for women with LS. Surveillance with gynecologic examination including assessment of symptoms, transvaginal pelvic ultrasonography, endometrial biopsy, and CA125 tumor marker assessment can be offered, but has not been shown to improve outcomes for these patients. Prophylactic hysterectomy with bilateral salpingo-oophorectomy performed after the completion of childbearing may be offered for gynecologic cancer prevention.
Lynch syndrome; endometrial cancer; ovarian cancer; surveillance; prophylactic surgery
Pregnancy following squamous cell carcinoma of the vulvar is rare. Its rarity is reflected by a paucity of cases reported in the literature. We report two cases of pregnancy following diagnosis and treatment for vulvar squamous cell carcinoma, and review eleven prior reported cases. In successfully treated vulvar cancer subsequent pregnancy is not shown to increase the risk of disease recurrence, and there appears to be no deleterious effects during the antenatal period. It is possible, when considering prior reports, that prior vulvectomy may increase the likelihood of delivery by caesarean section, though modifications in the surgical management of vulvar carcinoma may have decreased this risk.
Vulvar cancer; Squamous cell carcinoma; Radical vulvectomy; Pregnancy
During the first trimester of pregnancy fetal trophoblasts invade the maternal decidua, thereby remodeling the maternal spiral arteries. This process of trophoblast invasion is very similar to cancer cell invasion, with multiple signaling pathways shared between the two. Pregnancy-related diseases, e.g., pre-eclampsia, and cancer metastasis start with a decrease or increase in cellular invasion, respectively. Here, we investigate if first trimester placental explants can be used to identify epigenetic factors associated with changes in cellular invasion and their potential use as biomarkers. We show that the outgrowth potential of first trimester explants significantly correlates with promoter methylation of PRKCDBP and MMP2, two genes known to be differentially methylated in both placenta and cancer. The increase in methylation percentage of placental cells coincides with an increase in invasion potential. Subsequently, as a non-invasive marker must be detectable in blood, plasma samples of pregnant and non-pregnant women were analyzed. The MMP2 promoter showed high methylation levels in non-pregnant plasma samples, which decreased in pregnant plasma samples which also contain placental DNA. The decrease in methylated plasma DNA during pregnancy is most likely due to the fractional increase in unmethylated placental DNA. This suggests that the level of unmethylated DNA has the potential to be used as an invasion marker, where higher levels of unmethylated DNA indicate a lower invasion potential of trophoblasts. These proof of principle data provide evidence that human first trimester placental explants are an excellent ex vivo model system to identify (epigenetic) factors and thus potential biomarkers associated with changes in cellular invasion, e.g., to detect pregnancy-related diseases or cancer metastasis. To identify novel biomarkers the next step is to correlate naturally occurring variation in invasion potential to changes in (epigenetic) factors by genome-wide approaches such as massively parallel sequencing.
placenta; pre-eclampsia; cancer metastasis; invasion potential; biomarker
We investigated the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for restaging of treated uterine cervix squamous cell cancer with tumor maker elevation that was not explained by other conventional evaluation. We enrolled 32 cases who underwent PET/CT for the restaging of treated cervical cancer with tumor marker elevation that was not explained by recent conventional evaluation. All enrolled cases had squamous cell carcinoma. Increased tumor markers included squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA). PET/CT findings were determined by pathologic confirmation or clinical follow-up. We compared PET/CT accuracy and clinical parameters including normalization of tumor markers in both the SCC Ag elevation group and the CEA elevation group. The sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT in detecting recurrence were 100%, 83.3%, 82.4%, and 100%, respectively. Accuracy was significantly different between the SCC Ag elevation group and the CEA elevation group (p=0.0169). PET/CT with SCC Ag elevation was more accurate (100%) than PET/CT with CEA elevation (66.7%). Normalization of tumor markers was observed more often in the SCC Ag elevation group than in the CEA elevation group (p=0.0429). PET/CT showed high negative predictive value and sensitivity in the restaging of cervical cancer with unexplained tumor marker elevation. PET/CT was more accurate in patients with SCC Ag elevation than in those with CEA elevation.
Fluorodeoxyglucose F18; Positron-emission tomography and computed tomography; Recurrence
This paper reviews current screening techniques as well as novel biomarkers and their potential role in early detection of ovarian cancer. Ovarian cancer is one of the most common reproductive cancers and has the highest mortality rate amongst gynecologic cancers. Because most ovarian cancer diagnoses occur in the late stages of the disease, five-year survival rates fall below 20%. To improve survival rates and to lower mortality rates for ovarian cancer, improved detection at early stages of the disease is needed. Current screening approaches include tumor markers, ultrasound, or a combination. Efforts are underway to discover new biomarkers of ovarian cancer in order to surmount the obstacles in early-stage diagnosis. Among serum protein markers, HE4 and mesothelin can augment CA125 detection providing higher sensitivity and specificity due to the presence of these proteins in early-stage ovarian cancer. Detection testing that includes methylation of the MCJ gene and increased expression of vascular endothelial growth factor is correlated to poor prognosis and may predict patient survival outcome. Detection testing of biomarkers with long-term stability and combination panels of markers, will likely lead to effective screening strategies with high specificity and sensitivity for early detection of ovarian cancer.