| 1. |
- Isinger Ekstrand, Anna, et al.
(författare)
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Deranged Wnt signaling is frequent in hereditary nonpolyposis colorectal cancer.
- 2011
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Ingår i: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 10, s. 239-243
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Tidskriftsartikel (refereegranskat)abstract
- The Wnt signaling pathway is frequently deranged in colorectal cancer and is a key target for future preventive and therapeutic approaches. Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are characterized by wide-spread microsatellite instability, but show few gross genomic alterations. We characterized expression of the Wnt signaling pathway markers β-catenin, E-cadherin, TCF-4, and PTEN using immunohistochemical staining in colorectal cancers from individuals with HNPCC. Reduced membranous staining for β-catenin was found in 64% and for E-cadherin in 80% with strong correlation between these markers (P = 0.001). Nuclear β-catenin staining was detected in 19% of the tumors. Overexpression of TCF-4, which is activated by β-catenin, was found in 89% and downregulation of PTEN, which suppresses nuclear accumulation of β-catenin, was present in 54% of the tumors. In summary, altered expression of target molecules in the Wnt signaling pathway was demonstrated in the vast majority of the HNPCC-associated tumors, which support deranged Wnt-signaling as a central tumorigenic mechanism also in MMR defective colorectal cancer.
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| 2. |
- Ketabi, Zohreh, et al.
(författare)
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Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors
- 2011
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 121:3, s. 462-465
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Tidskriftsartikel (refereegranskat)abstract
- 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. (C) 2011 Elsevier Inc. All rights reserved.
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| 3. |
- Klarskov, Louise, et al.
(författare)
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Challenges in the Identification of MSH6-Associated Colorectal Cancer: Rectal Location, Less Typical Histology, and a Subset With Retained Mismatch Repair Function.
- 2011
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Ingår i: American Journal of Surgical Pathology. - 1532-0979. ; 35:9, s. 1391-1399
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Tidskriftsartikel (refereegranskat)abstract
- Identification of Lynch syndrome tumors is challenging. This relates particularly to MSH6-associated cases, which show reduced penetrance of colorectal cancer and a higher age at diagnosis. We recorded the clinical and morphologic features of 52 MSH6-associated colorectal cancers in comparison with MLH1/MSH2-mutant tumors and sporadic mismatch repair-deficient cancers. In the MSH6 subset, we confirmed a higher age (median, 56 y) at diagnosis and found a significantly larger proportion (25%) of rectal cancers. Presence of dirty necrosis was the sole histologic component that significantly differed between MSH6 and MLH1/MSH2 tumors. Compared with the sporadic mismatch repair-defective cohort, MSH6 cases had a lower prevalence of tumor-infiltrating lymphocytes and Crohn-like reactions. Mismatch repair defects were identified in 92% of MSH6 tumors, with high concordance between microsatellite instability and loss of immunohistochemical MSH6 expression. The remaining 8% showed a mismatch repair-stable phenotype, which suggests that analysis of additional tumors might be considered in families suspected of Lynch syndrome.
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| 4. |
- Petersen, Helle Vendel, et al.
(författare)
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Limited impact on self-concept in individuals with Lynch syndrome; results from a national cohort study
- 2011
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Ingår i: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 10:4, s. 633-639
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Tidskriftsartikel (refereegranskat)abstract
- An increasing number of individuals seek genetic counseling and hereby learn about hereditary cancer in the family. Lynch syndrome is associated with an inherited high risk for colorectal and gynecological cancer, but knowledge about how family members at risk perceive their situation is limited. We used the national Danish HNPCC register to collect data on self-concept from 413 individuals with Lynch syndrome. The recently developed Lynch syndrome self-concept scale contains 20 items within two subscales related to stigma-vulnerability and bowel symptom-related anxiety. Significantly higher total scores, indicating a greater impact on self-concept, were reported by females and by individuals with experience from cancer in close relatives, whereas individuals with less formal education scored significantly higher on the stigma and vulnerability subscale. Scores in the upper quartile were more often reported by women (odds ratio 1.8) and by individuals with less education (OR 1.8). This study provides the first extended use of the Lynch syndrome self-concept scale and suggests that the majority of the Danish mutation carriers adapt well to the situation, though knowledge about the increased risk of cancer seem to have a greater impact in females, individuals with less education and those with experience of cancer in close relatives.
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| 5. |
- Vendel Petersen, Helle, et al.
(författare)
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Validation of a Self-Concept Scale for Lynch Syndrome in Different Nationalities
- 2011
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Ingår i: Journal of Genetic Counseling. - : Wiley. - 1059-7700 .- 1573-3599. ; 20:3, s. 308-313
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Tidskriftsartikel (refereegranskat)abstract
- Learning about hereditary cancer may influence an individual's self-concept, which otherwise represents a complex but stable cognitive structure. Recently, a 20-statement self-concept scale, with subscales related to stigma-vulnerability and bowel symptom-related anxiety, was developed for Lynch syndrome. We compared the performance of this scale in 591 mutation carriers from Denmark, Sweden and Canada. Principal component analysis identified two sets of linked statements-the first related to feeling different, isolated and labeled, and the second to concern and worry about bowel changes. The scale performed consistently in the three countries. Minor differences were identified, with guilt about passing on a defective gene and feelings of losing one's privacy being more pronounced among Canadians, whereas Danes more often expressed worries about cancer. Validation of the Lynch syndrome self-concept scale supports its basic structure, identifies dependence between the statements in the subscales and demonstrates its applicability in different Western populations.
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