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1.
Cancer Lett ; 312(1): 43-54, 2011 Dec 15.
Article in English | MEDLINE | ID: mdl-21906875

ABSTRACT

Pathogenetic pathways of gastrointestinal stromal tumors (GIST) lacking mutations in KIT and PDGFRA (∼15%) are still poorly studied. Nearly nothing is known about PI3K alterations in GISTs and only a few GISTs with BRAF mutations have been reported. BRAF mutations (V600E) were found in 3/87 tumors (3.5%) concomitantly were wild type for KIT and PDGFRA. No mutations were detected in KRAS, NRAS, and FGFR3. For the first-time we demonstrated a PIK3CA mutation (H1047L) simultaneously occurring with a 15-bp deletion in KIT exon 11 in one tumor. We suggest that BRAF mutations are of pathogenetic significance in wild type GISTs. The PI3K pathway should be assessed in future studies.


Subject(s)
Gastrointestinal Stromal Tumors/enzymology , Gastrointestinal Stromal Tumors/genetics , Mutation , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-kit/genetics , Receptor, Platelet-Derived Growth Factor alpha/genetics , Adult , Aged , Aged, 80 and over , Amino Acid Sequence , Class I Phosphatidylinositol 3-Kinases , DNA Mutational Analysis , Female , Gastrointestinal Stromal Tumors/pathology , Humans , Male , Middle Aged , Molecular Sequence Data , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins B-raf/metabolism , Proto-Oncogene Proteins c-kit/metabolism , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Signal Transduction
2.
Clin Gastroenterol Hepatol ; 9(7): 590-4, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21320641

ABSTRACT

BACKGROUND & AIMS: Oncologic surgery is recommended after endoscopic resection of submucosal invasive T1 colorectal carcinomas if patients are considered to be at high risk for tumor recurrence or metastasis. However, there are sparse data on the outcome of high-risk patients treated only by endoscopy. METHODS: Data were collected from 474 patients who underwent endoscopic resection for T1 colorectal cancers from 1974-2002 at Neuperlach Hospital in Munich, Germany. Patient files were reviewed, and patients or referring physicians were contacted to assess outcomes during a follow-up period of at least 24 months (n = 390). Histopathology and endoscopy factors associated with an unfavorable outcome (local recurrence of tumors, metastasis, or death from colorectal cancer) were assessed. RESULTS: Of the 390 patients followed, 141 received oncologic surgery, and 249 did not; overall, 10% had an unfavorable outcome (39/390). Multivariate regression analysis revealed that lymphatic vessel infiltration, poor grading of tumor stage, and incomplete endoscopic resection were risk factors for unfavorable outcomes (odds ratios, 7.8, 3.4, and 2.6, respectively). If these risk factors were applied to patients who did not receive oncologic surgery, negative predictive values for an unfavorable outcome were 94.6% for lymphatic vessel infiltration, 94.2% for poor grading of tumor stage, and 96.5% for incomplete endoscopic resection; positive predictive values were 44.4%, 42.9%, and 19.6%, respectively. CONCLUSIONS: Tumor infiltration of lymphatic vessels is the greatest risk factor for an unfavorable outcome after endoscopic resection for colorectal carcinoma. However, its positive predictive value is low. The decision to perform surgery after endoscopic resection of T1 colorectal cancers should be made on the basis of specific features of each patient.


Subject(s)
Colonic Polyps/pathology , Colonic Polyps/surgery , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Endoscopy, Gastrointestinal/methods , Aged , Colonic Polyps/mortality , Colorectal Neoplasms/mortality , Disease Progression , Female , Germany , Histocytochemistry , Humans , Incidence , Male , Middle Aged , Neoplasm Metastasis , Recurrence , Risk Factors , Treatment Outcome
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