Risk stratification of patients diagnosed with gastrointestinal stromal tumor

Summary Background Adjuvant imatinib mesylate prolongs recurrence-free survival (RFS) after resection of localised primary gastrointestinal stromal tumours (GIST). We aimed to develop a nomogram to predict RFS after surgery in the absence of adjuvant therapy to help guide patient selection for adjuvant imatinib therapy. Methods A nomogram to predict RFS based on tumour size (cm), location (stomach, small intestine, colon/rectum, or other), and mitotic index ( Findings The nomogram had a concordance probability of 0·78 (SE 0·02) in the MSKCC dataset, and 0·76 (0·03) and 0·80 (0·02) in the validation cohorts. Nomogram predictions were well calibrated. Inclusion of tyrosine kinase mutation status in the nomogram did not improve its discriminatory ability. Concordance probabilities of the nomogram were better than those of the two NIH staging systems (0·76 [0·03] vs 0·70 [0·04, p=0·04] and 0·66 [0·04, p=0·01] in the GEIS validation cohort; 0·80 [0·02] vs 0·74 [0·02, p=0·04] and 0·78 [0·02, p=0·05] in the Mayo cohort) and similar to those of the AFIP-Miettinen staging system (0·76 [0·03] vs 0·73 [0·004, p=0·28] in the GEIS cohort; 0·80 [0·02] vs 0·76 [0·003, p=0·09] in the Mayo cohort). Nomogram predictions of RFS seemed better calibrated than predictions made with the AFIP-Miettinen system. Interpretation The nomogram accurately predicts RFS after resection of localised primary GIST and could be used to select patients for adjuvant imatinib therapy. Funding National Cancer Institute, Bethesda, MD, USA.

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Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis

Minichromosome maintenance (MCM) proteins are essential for the process of DNA replication, functioning as license components for the S-phase of cell-cycle initiation and further exerting weak helicase activity to unwind DNA from its supercoiled state at replication forks. The requirement for MCM proteins in cycling cells and their absence in quiescent ones supports evidence for their potential clinical application as cell proliferation markers. In the last few years, aside from their utility as cell proliferation markers, the assessment of MCM expression levels in diverse human malignancies has been the focus of extensive research in an aim to facilitate tumor diagnosis and prognosis in clinical settings. The present article aims to review the available data so far concerning the clinical significance of MCM protein expression in human neoplasia in comparison to conventional proliferative markers. A review of the literature revealed that MCM expression is associated with important clinicopathological parameters for patient management and also exhibits significant diagnostic and prognostic value in several malignancies. MCMs are characterized by higher specificity and sensitivity than the conventional proliferative markers, such as Ki-67 and PCNA, and are thus considered as diagnostic and prognostic tools of greater clinical significance in several types of human malignancy.

https://digitum.um.es/xmlui/bitstream/10201/42593/1/MCM%20proteins%20as%20diagnostic%20and%20prognostic%20tumor%20markers%20in%20the%20clinical%20setting.pdf

MCM proteins as diagnostic and prognostic tumor markers in the clinical setting

Hypothesis A gastrointestinal stromal tumor (GIST) staging system can be created with the Surveillance, Epidemiology and End Results (SEER) database. Design A review of records in the SEER database from 2537 patients with GISTs from June 1, 1977, through August 1, 2004. Patients and Methods Patients were compared using all available clinicopathologic factors, and a TGM (tumor, grade, metastasis) staging system was created according to these parameters. Survival data were analyzed using Kaplan-Meier methods, log-rank analyses, and Cox regression models. Results Median follow-up time was 21 months, 47.6% of patients were men, and the median age was 64 years; 5.0% had lymph node involvement, and 22.6% had distant metastasis. Tumor size (T1, ≤70 mm; T2, >70 mm; P P P Conclusions A staging system for GISTs that provides valuable prognostic information was developed. Further work to refine this system and validate it with other data sets should be undertaken. Mitotic index and standardized reporting may provide additional prognostic information and should be recorded for all tumors so that the most accurate staging system can be created.

https://jamanetwork.com/journals/jamasurgery/articlepdf/405126/sws90001_670_678.pdf

An evaluation of 2537 gastrointestinal stromal tumors for a proposed clinical staging system.

Gastrointestinal stromal tumor has received a lot of attention over the last 10 years due to its unique biologic behavior, clinicopathological features, molecular mechanisms, and treatment implications. GIST is the most common mesenchymal neoplasm in the gastrointestinal tract and has emerged from a poorly understood and treatment resistant neoplasm to a well-defined tumor entity since the discovery of particular molecular abnormalities, KIT and PDGFRA gene mutations. The understanding of GIST biology at the molecular level promised the development of novel treatment modalities. Diagnosis of GIST depends on the integrity of histology, immunohistochemistry and molecular analysis. The risk assessment of the tumor behavior relies heavily on pathological evaluation and significantly impacts clinical management. In this review, historic review, epidemiology, pathogenesis and genetics, diagnosis, role of molecular analysis, prognostic factor and treatment strategies have been discussed.

/pdf/gastrointestinal-stromal-tumor-10oynfwk7l.pdf

Gastrointestinal stromal tumor

A modification of NIH consensus criteria to better distinguish the highly lethal subset of primary localized gastrointestinal stromal tumors: a subdivision of the original high-risk group on the basis of outcome.

Background
Inactivation of p16INK4A promotes G1/S progression of cell cycle. Minichromosome maintenance protein-2 (Mcm2), a novel cell proliferation marker, is known to better correlate with clinical outcomes than Ki-67 in many carcinomas. Since gastrointestinal stromal tumors (GISTs) sometimes remains challenging in prognostication, we analyzed the utility of these three markers in GISTs.

Immunohistochemical expression of p16INK4A, Ki-67, and Mcm2 proteins in gastrointestinal stromal tumors: prognostic implications and correlations with risk stratification of NIH consensus criteria.

David Lu

Papers

A modification of NIH consensus criteria to better distinguish the highly lethal subset of primary localized gastrointestinal stromal tumors: a subdivision of the original high-risk group on the basis of outcome.

Immunohistochemical expression of p16INK4A, Ki-67, and Mcm2 proteins in gastrointestinal stromal tumors: prognostic implications and correlations with risk stratification of NIH consensus criteria.