Abstract A11: Loss of LKB1 is an early event in high-grade serous carcinoma
Notice bibliographique
Résumé
Abstract Background: LKB1 is a ubiquitously expressed serine/threonine protein kinase recently ranked sixteenth on the list of top cancer genes. Inactivating germ-line mutations in LKB1 gene on chromosome 19p13.3 found in 60–70% of patients with Peutz-Jeghers syndrome (PJS), leading to increased risk of developing cancers of epithelial origin. Loss of LKB1 protein with underlying LKB1 gene methylation previously found in high-grade breast carcinoma – low expression associated with shorter relapse-free survival. Heterozygous mutations of LKB1 and p53 genes cooperate in the acceleration of tumorigenesis in mice. High-grade serous ovarian cancer (HGSC) is rarely diagnosed at an early and potentially curable stage, effective early detection and preventative strategies are few. In a previously published microarray study, we observed that LKB1 mRNA was significantly lower in Fallopian tube cancers and HGSC. Recently the discovery of occult invasive and intraepithelial tubal carcinomas in BRCA1 mutation carriers, who are at high risk of serous cancer, undergoing prophylactic surgery has focused attention on the fallopian tube epithelium as the cell of origin and has led to the reporting of putative serous cancer precursor lesions. We therefore, sought to determine the expression of LKB1 in different histological subtypes of ovarian cancer and in early lesions; and the effect of loss of LKB1 on fallopian tube epithelial cells in vitro. Methodology: Archived sections of ovarian tumors were reviewed, paraffin blocks selected, and tissue microarrays created using triplicate 0.6 mm cores. The major histological types included were: high grade serous (n=201), non-serous (n=87), and low grade (micropapillary) (n=12) carcinomas, serous tumors of low malignant potential (n=26) and STICS (n=15). Immunohistochemistry for LKB1 protein (Santa Cruz mouse mAb sc-32245) was performed using standard techniques. Percentage of tumor cells with positive cytoplasmic staining (0–3), staining intensity (0–3) and histoscores were determined by viewing digitalized images with Aperio ImageScope software. A combined score of > 4 was considered positive. Fishers exact test with 95% confidence intervals was used to determine the significance of results. Fallopian tube epithelial cells were established from freshly digested tissue and infected with shRNA targeting LKB1. In vitro assays to determine proliferation and malignant transformation were used. Results: Loss of cytoplasmic LKB1 protein expression is more frequently observed in sporadic and hereditary high-grade serous carcinomas compared to other histological types, including low-grade serous carcinoma and serous tumors of low malignant potential. LKB1 may be exclusively involved in the high-grade serous oncogenic pathway and not in the development of low-grade serous carcinoma. Loss of LKB1 in early lesions was observed in 15/15 cases and indicates a role for in sporadic HGSC tumorigenesis in corporation with previously identified oncogenes. The frequency of LKB1 loss in high-grade tumors (67–69%) is similar to frequency of p53 mutations previously observed (70%). Citation Information: Cancer Prev Res 2011;4(10 Suppl):A11.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».