Danish guidelines for management of non-APC-associated hereditary polyposis syndromes.

Hereditary Polyposis Syndromes are a group of rare, inherited syndromes characterized by the presence of histopathologically specific or numerous intestinal polyps and an increased risk of cancer. Some polyposis syndromes have been known for decades, but the development in genetic technologies has allowed the identification of new syndromes.. The diagnosis entails surveillance from an early age, but universal guideline on how to manage and surveille these new syndromes are lacking. This paper represents a condensed version of the recent guideline (2020) from a working group appointed by the Danish Society of Medical Genetics and the Danish Society of Surgery on recommendations for the surveillance of patients with hereditary polyposis syndromes, including rare polyposis syndromes.

The results of gynecologic surveillance in families with hereditary nonpolyposis colorectal cancer.

OBJECTIVE: We aimed to estimate the incidence rate of endometrial cancer (EC) and to evaluate the results of EC-surveillance in hereditary nonpolyposis colorectal cancer (HNPCC) families. METHODS: All at-risk women recommended for EC-surveillance by the HNPCC-register-2959 women (19,334women years)-were included. Data on EC-surveillance were available for 871 women (6894women years), who had performed 1945 surveillance visits. The average surveillance period was 7.9 (range 0.1-21.7) years and 46% of the women had had less than 3years between their visits. RESULTS: During 19,334women years, 60 women with gynecological malignancies or premalignancies were diagnosed. Thirty-nine women had EC. Of these, 31 were from families with identified MMR gene mutations with the median age at diagnosis of 54 (39-83) years (Incidence Rate, IR=0.63 per 100women years) and four women from each Amsterdam (AMS)-positive and AMS-like families (median age 64 (55-73) years, IR=0.06 and 0.05 per 100women years, respectively, p<.0001). Among the 871 surveilled women, 13 EC were found: 7/13 cases were diagnosed by surveillance examination-two as prevalent cancers, diagnosed at the first visit-and 6/13 based on symptoms. In addition, five complex atypical hyperplasias and four ovarian cancers (OCs) were diagnosed. All these women were MMR mutation carriers. CONCLUSION: Based on 19,334women years of EC-surveillance, our analysis provides a thorough estimation of the EC risk in women with an MMR mutation, or suspected of having Lynch syndrome. We conclude that EC surveillance should only be targeted at MMR-mutation carriers.

New expert advice on cancer in pregnancy.

Cancer in pregnancy is rare, and most physicians lack knowledge in handling pregnant cancer patients. This review summarises the present knowledge on this condition. In the Netherlands, an Advisory Board on Cancer in Pregnancy was established in 2012. The board supports Dutch physicians' decisions in the management of pregnant patients with cancer. In 2021 the International Advisory Board on Cancer in Pregnancy was established, and in continuation, the Danish Advisory Board on Cancer in Pregnancy (DABCIP) has now been founded. DABCIP consists of 22 members from 13 different medical disciplines.

Ovarian cancer linked to Lynch syndrome typically presents as early-onset, non-serous epithelial tumors.

OBJECTIVE: Heredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized. METHODS: We characterized clinical features, tumor morphology and mismatch repair defects in all ovarian cancers identified in Swedish and Danish Lynch syndrome families. RESULTS: In total, 63 epithelial ovarian cancers developed at mean 48 (range 30-79) years of age with 47% being early stage (FIGO stage I). Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented. The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed. CONCLUSION: The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch syndrome typically presents at young age as early-stage, non-serous tumors, which implicates that a family history of colorectal and endometrial cancer should be specifically considered in such cases.

[New hereditary polyposis syndromes in the patient with intestinal polyps].

Hereditary polyposis syndromes (HPS) are a group of rare, inherited syndromes characterised by the presence of histopathological specific or numerous intestinal polyps and a high risk of intestinal and extraintestinal cancer. During the last decade, several new HPS have been discovered, as it is possible to detect pathogenic germline variants in genes not previously known to be associated with polyposis. This review summarises the current knowledge on the syndromes and discusses genetic testing as part of the diagnostic pipeline when suspecting a polyposis syndrome.

Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome.

Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic ovarian cancers point to alternative preferred tumorigenic routes and suggest that genetic discriminators may be relevant for molecular diagnostics and targeted therapeutics.

Awareness of endometrial cancer risk and compliance with screening in hereditary nonpolyposis colorectal cancer.

OBJECTIVE: Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a 40-60% lifetime risk for endometrial cancer. Guidelines in Denmark recommend gynecologic screening for female members of families with HNPCC. We estimated the knowledge of endometrial cancer risk and identified possible predictors of compliance with the screening among women from families with HNPCC. METHODS: A questionnaire exploring the knowledge of endometrial cancer risk and compliance with screening was sent to 707 women from families with HNPCC who had been recommended endometrial cancer surveillance. The response rate after one reminder was 86% (606 of 707). Data were analyzed by simple and multivariable logistic regression models. RESULTS: Four hundred seventy-one women were included in the final analyses; 65% reported being aware of the increased risk of endometrial cancer. The awareness was significantly greater among women with high educational level (81%; P<.001), women who had received genetic counseling (75%; P<.001), women with family history of gynecologic cancer (76%; P<.001), and those with high perceived endometrial cancer risk (77%; P<.001). Overall, 67% had participated in gynecologic screening. No significant differences were found in compliance regarding women's educational level or their family risk classification. Analyses of data in a multivariable logistic regression model showed that knowledge of endometrial cancer risk was the most important predictor for positive compliance with the gynecologic screening (odds ratio 4.86, 95% confidence interval 3.05-7.74). CONCLUSION: Women's awareness of endometrial cancer risk is the most important predictor of their compliance with gynecologic screening in families with HNPCC. LEVEL OF EVIDENCE: II.

Expression of CPEB, GAPDH and U6snRNA in cervical and ovarian tissue during cancer development.

Persistent infection with high-risk human papillomavirus (HPV) and expression of the proteins E6 and E7 is a prerequisite for development of cervical cancer. The distal non-coding part of E6/E7 messengers from several HPV types is able to downregulate synthesis of a reporter gene through mechanisms with involvement of cytoplasmic polyadenylation elements (CPEs) in the messengers. We here show that the mRNA levels of one of the four known CPE-binding proteins (CPEBs), the CPEB3, were downregulated in HPV-positive cervical cancers, whereas in ovarian cancer the CPEB1 mRNA level was downregulated. In addition, we showed that the RNA levels of the widely used reference marker GAPDH were upregulated in both cancer forms, and the level of the reference marker U6snRNA was upregulated in cervical cancers. Moreover, a possible correlation between the degree of U6snRNA upregulation and cervical cancer propagation was shown. These changes observed in CPEB1 and CPEB3 might indicate regulatory functions of CPEBs in cancer development of HPV-positive and HPV-negative tumors, respectively, and the U6snRNA, GAPDH mRNA and CPEB1 mRNA levels may be useful as tumor markers for genital cancers although further investigations are needed.

[Self reported quality of life among patients referred to a gynaecologic ward with urinary incontinence]. / Selvrapporteret livskvalitet hos patienter med urininkontinens henvist til en gynaekologisk afdeling.

INTRODUCTION: Urinary incontinence (UI) represents a frequent symptom among women of all ages. However, very few women are admitted to a hospital or clinic because of UI. The aim of the paper was to characterize women admitted to hospital because of UI in respect to symptoms and self reported quality of life. MATERIALS AND METHODS: The study comprised all 174 women admitted to a gynaecologic ward due to lower urinary tract symptoms (LUTS) in the period from 1 November 1999 to 1 August 2001. A total of 142 women (82%) completed validated questionnaires on symptoms and quality of life and were included in this analysis. RESULTS: The median age was 59 years. The majority (97%) had UI at least once a week. Many patients reported other LUTS--in particular nocturia (87%) and urgency (81%). Two-thirds of the women experienced UI as a major problem. The single most affected factor in terms of quality of life--mental well being--was compromised in two-thirds of the cases. Half of all women were incontinent for flatus, one-third for loose stools and one tenth for normal stools occasionally or more frequently. One out of four women experienced anal incontinence as a major problem. CONCLUSION: The study shows that the quality of life among women referred to a gynaecologic ward because of LUTS is severely affected. Moreover, the study demonstrates a close association between UI symptoms and symptoms indicating pelvic floor malfunction, such as LUTS and anal incontinence.