Introduction: Dorsophilia protein, mothers against decapentaplegic homolog 4 (SMAD4) is a key mediator in the transforming growth factor (TGF)-β signaling pathway and SMAD4 gene mutations are thought to play a critical role in colorectal cancer (CRC) progression. However, little is known about its influence on survival in patients undergoing resection for colorectal liver metastases (CLM).
Methods: Between 2005 and 2015, all patients with known SMAD4 mutation status who underwent resection of CLM were identified. Patients with SMAD4 mutation were compared to those with SMAD4 wild type. Next, the prognostic value of SMAD4 mutation was validated in a separate cohort of patients with synchronous stage IV CRC who underwent systemic therapy alone.
Results: Of 278 patients, 37 (13%) were SMAD4 mutant while 241 (87%) were wild type. Overall survival (OS) after hepatic resection was worse in SMAD4-mutant patients compared to SMAD4 wild type (OS rate at 3 years, 62% vs. 82%; P < 0.0001). Independent predictors for worse OS were poor differentiation (hazard ratio [HR] 2.586; P = 0.007), multiple tumors (HR 1.970; P = 0.01), diameter greater than 3 cm (HR 1.752; P = 0.017), R1 margin status (HR 2.452; P = 0.014), RAS mutation (HR 2.044; P = 0.002), and SMAD4 mutation (HR 2.773; P < 0.0001). Among 237 patients in the validation cohort, SMAD4-mutations were significantly associated with worse 3-year OS rate (22% vs. 38%; P = 0.012) and was an independent predictor for worse OS (HR, 1.647; P = 0.032).
Conclusion: SMAD4 mutation is independently associated with worse outcomes among patients undergoing resection of CLM.
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http://dx.doi.org/10.1016/j.ejso.2018.02.247 | DOI Listing |
Neoplasia
December 2024
AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, Casalnuovo Di Napoli 80013, Italy.
Background: Oligo-metastatic disease (OMD) in colon cancer patients exhibits distinct clinical behavior compared to poly-metastatic disease (PMD), with a more responsive and indolent course. This study aims to identify clinical and biological factors uniquely associated with oligo-metastatic behavior.
Methods: Metastatic colon cancer patients from an academic center underwent genetic characterization.
Unlabelled: The study aimed to identify the clinically relevant gene variants in colon adenocarcinoma samples of Ukrainian patients using the NGS Comprehensive Cancer Panel (CCP) to implement them conveniently in clinical practice.
Methods: We have studied 20 samples of Ukrainian patients with colorectal adenocarcinomas of various differentiation grades. To identify the clinically relevant gene variants, the CCP data were filtered using the Franklin by Genoox database.
BMC Cancer
December 2024
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
Background: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection of precursor lesions or early-stage cancer could hamper cancer development or improve survival rates. Liquid biopsy, which detects tumor biomarkers, such as mutations, in blood, is a promising avenue for cancer screening.
View Article and Find Full Text PDFSemin Thromb Hemost
December 2024
Gastroenterology Department, HHT European Reference Center, ASST Ospedale Maggiore Crema, Crema, Italy.
Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular disorder with highly variable penetrance, affecting up to 1 in 5,000 individuals. It is characterized by the presence of abnormal blood vessels that can lead to excessive bleeding-most frequently recurrent nosebleeds (epistaxis), skin and mucosal telangiectasias (small, dilated blood vessels), as well as arteriovenous malformations (AVMs) that can form in various organs, particularly the lungs, liver, and brain. HHT is caused by loss-of-function mutations in the BMP9-10/ENG/ALK1/SMAD4 signaling pathway, an important mediator of vascular quiescence.
View Article and Find Full Text PDFAm J Surg Pathol
December 2024
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
Gastric-type endocervical adenocarcinomas (GAS) are aggressive HPV-independent neoplasms with molecular alterations in TP53 , STK11 , CDKN2A, and SMAD4 . Claudin-18 (CLDN18) has emerged as a useful marker to distinguish GAS from HPV-associated neoplasia. Its role in separating GAS from benign proliferations and exuberant endocervical glands is unknown.
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