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Ran P, Tan T, Zhou H, Li J, Yang H, Li J, Zhang J. Nomogram for Predicting Recurrence-Free Survival of Primary Localized Gastrointestinal Stromal Tumor. J Pers Med 2023; 13:498. [PMID: 36983680 PMCID: PMC10052207 DOI: 10.3390/jpm13030498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 03/02/2023] [Accepted: 03/08/2023] [Indexed: 03/12/2023] Open
Abstract
PURPOSE This study aimed to establish a new nomogram that predicts recurrence-free survival (RFS) after a complete surgical resection of primary localized gastrointestinal stromal tumors (GISTs); it also aimed to evaluate the discrimination, calibration, and clinical utility of the decision-making nomogram. METHODS The clinicopathological data of patients with primary localized GISTs at the First Affiliated Hospital of Chongqing Medical University from January 2000 to June 2022 were retrospectively analyzed. The clinicopathological data were randomly split into two sets (7:3 ratio) for training and validation. Suitable variables for the construction of a nomogram for the 1-, 3-, and 5-year RFS were selected using univariate and multivariate Cox regression analyses. Receiver operating characteristic (ROC) analysis and a concordance index (C-index) were used to quantify the discrimination of the nomogram and were compared with four commonly used prognostic scoring systems: Memorial Sloan Kettering Cancer Center prognostic nomogram, National Institutes of Health-Fletcher staging system, Chen's prognostic nomogram, and Air Forces Institute of Pathology risk criteria-Miettinen staging system. The calibration and clinical utility for the decision-making nomogram were validated using calibration curves and decision curves, respectively. RESULTS In total, 641 patients were screened and analyzed in this retrospective, observational study. RFS was significantly related to tumor size, mitotic count, gender, DOG-1, and adjuvant therapy with imatinib according to the results of the multivariate and univariate Cox analyses. The nomogram was constructed using the above variables (all p < 0.05) for the 1-, 3-, and 5-year RFS. In the training set, the 1-, 3-, and 5-year ROC and C-index values of the nomogram were 0.868, 0.838, 0.816, and 0.830, respectively. For internal validation, we performed model fitting on the validation set, and the 1-, 3-, and 5-year ROC and C-indices were 0.977, 0.845, 0.869, and 0.849, respectively. Among the five GIST prognostic scoring systems, our nomogram had almost all the largest area under these decision curves and had a good calibration capability. CONCLUSIONS The newly constructed nomogram based on tumor size, gender, mitotic count, DOG-1, and adjuvant treatment with imatinib exhibited an excellent performance and may serve as a prognostic scoring system to support therapeutic decision-making and individualized treatment for GISTs in China.
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Affiliation(s)
- Pan Ran
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Tao Tan
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Hui Zhou
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jinjin Li
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Hao Yang
- Department of Internal Medicine, Chongqing Key Laboratory of Translation Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Juan Li
- Department of Pharmacy, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jun Zhang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
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Guan SH, Wang Q, Ma XM, Qiao WJ, Li MZ, Lai MG, Wang C. Development of an innovative nomogram of risk factors to predict postoperative recurrence of gastrointestinal stromal tumors. World J Gastrointest Surg 2022; 14:940-949. [PMID: 36185569 PMCID: PMC9521461 DOI: 10.4240/wjgs.v14.i9.940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 07/02/2022] [Accepted: 08/07/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND There are many staging systems for gastrointestinal stromal tumors (GISTs), and the risk indicators selected are also different; thus, it is not possible to quantify the risk of recurrence among individual patients.
AIM To develop and internally validate a model to identify the risk factors for GIST recurrence after surgery.
METHODS The least absolute shrinkage and selection operator (LASSO) regression model was performed to identify the optimum clinical features for the GIST recurrence risk model. Multivariable logistic regression analysis was used to develop a prediction model that incorporated the possible factors selected by the LASSO regression model. The index of concordance (C-index), calibration curve, receiver operating characteristic curve (ROC), and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the predictive model. Internal validation of the clinical predictive capability was also evaluated by bootstrapping validation.
RESULTS The nomogram included tumor site, lesion size, mitotic rate/50 high power fields, Ki-67 index, intracranial necrosis, and age as predictors. The model presented perfect discrimination with a reliable C-index of 0.836 (95%CI: 0.712-0.960), and a high C-index value of 0.714 was also confirmed by interval validation. The area under the curve value of this prediction nomogram was 0.704, and the ROC result indicated good predictive value. Decision curve analysis showed that the predicting recurrence nomogram was clinically feasible when the recurrence rate exceeded 5% after surgery.
CONCLUSION This recurrence nomogram combines tumor site, lesion size, mitotic rate, Ki-67 index, intracranial necrosis, and age and can easily predict patient prognosis.
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Affiliation(s)
- Shi-Hao Guan
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, China
- Medical College, Qinghai University, Xining 810001, Qinghai Province, China
| | - Qiong Wang
- Department of Medical Oncology, The Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China
| | - Xiao-Ming Ma
- Department of Gastrointestinal Tumor Surgery, The Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China
| | - Wen-Jie Qiao
- Department of Gastrointestinal Tumor Surgery, The Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China
| | - Ming-Zheng Li
- Department of Gastrointestinal Tumor Surgery, The Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China
| | - Ming-Gui Lai
- Department of Gastrointestinal Tumor Surgery, The Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China
| | - Cheng Wang
- Department of Gastrointestinal Tumor Surgery, The Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China
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Jansen K, Farahi N, Büscheck F, Lennartz M, Luebke AM, Burandt E, Menz A, Kluth M, Hube-Magg C, Hinsch A, Höflmayer D, Weidemann S, Fraune C, Möller K, Lebok P, Sauter G, Simon R, Uhlig R, Wilczak W, Jacobsen F, Minner S, Krech R, Clauditz T, Bernreuther C, Dum D, Krech T, Marx A, Steurer S. DOG1 expression is common in human tumors: A tissue microarray study on more than 15,000 tissue samples. Pathol Res Pract 2021; 228:153663. [PMID: 34717148 DOI: 10.1016/j.prp.2021.153663] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 10/17/2021] [Indexed: 02/03/2023]
Abstract
DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n = 1002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p < 0.0001) and absence of HPV infection in squamous cell carcinomas (p = 0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.
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Affiliation(s)
- Kristina Jansen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Nagina Farahi
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Franziska Büscheck
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Maximilian Lennartz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas M Luebke
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Eike Burandt
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anne Menz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Martina Kluth
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Claudia Hube-Magg
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andrea Hinsch
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Doris Höflmayer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sören Weidemann
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Fraune
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Katharina Möller
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Patrick Lebok
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Sauter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ronald Simon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Ria Uhlig
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Waldemar Wilczak
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frank Jacobsen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sarah Minner
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Rainer Krech
- Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - Till Clauditz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Bernreuther
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - David Dum
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Till Krech
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - Andreas Marx
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Huang C, Li CG, Zhang P, Yang WC, Lin Y, Shuai XM, Gao JB, Cai M, Tao KX. Duodenal gastrointestinal stromal tumors: A retrospective study based on a 13 years experience of a single center in China. Asia Pac J Clin Oncol 2021; 17:506-512. [PMID: 33567161 DOI: 10.1111/ajco.13509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 10/03/2020] [Indexed: 01/10/2023]
Abstract
AIM Duodenal gastrointestinal stromal tumors (GISTs) constitute a small rare subset. This study aims to analyze the prognostic differences between duodenal and jejunoileal GISTs and evaluate the clinical treatment and prognostic characteristics of patients with duodenal GISTs. METHODS Data of patients with primary duodenal or jejunoileal GISTs were collected. Patients were matched through propensity score matching (PSM). Perioperative and long-term outcomes of patients with duodenal GISTs were compared based on surgical approach. RESULTS Altogether, 101 duodenal and 219 jejunoileal GISTs were identified. In patients with duodenal GISTs, 79 (78%) underwent local resection (LR) and 22 (22%) underwent pancreaticoduodenectomy (PD). Patients undergoing PD had a longer postoperation stay (18.5 vs 13 days, P = 0.001) and more complications (Clavien-Dindo I-II complications for PD vs LR, 31.8 vs 15.2%; Clavien-Dindo III-V complications for PD vs LR, 22.7 vs. 2.5%; P < 0.001). There was no difference in recurrence-free survival (RFS) (P = 0.8) or overall survival (OS) (P = 0.9) when comparing patients who underwent LR versus PD. Multivariable analysis showed that tumor size >5 cm was the only independent predictor of shorter RFS (P = 0.004) and OS (P = 0.012). After matching, there was no significant difference in RFS and OS between patients with duodenal versus jejunoileal GISTs (both P > 0.05). CONCLUSION The prognosis of duodenal and jejunoileal GISTs are similar. Recurrence and OS of duodenal GISTs primarily depend on tumor size. For duodenal GISTs, LR is associated with comparable long-term survival when compared to PD, but with superior short-term outcomes.
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Affiliation(s)
- Cheng Huang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Cheng-Guo Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Peng Zhang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Wen-Chang Yang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Yao Lin
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Xiao-Ming Shuai
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Jin-Bo Gao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Ming Cai
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Kai-Xiong Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
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Yi M, Xia L, Zhou Y, Wu X, Zhuang W, Chen Y, Zhao R, Wan Q, Du L, Zhou Y. Prognostic value of tumor necrosis in gastrointestinal stromal tumor: A meta-analysis. Medicine (Baltimore) 2019; 98:e15338. [PMID: 31027106 PMCID: PMC6831433 DOI: 10.1097/md.0000000000015338] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND AND AIMS There is currently no consensus regarding the influence of tumor necrosis on the prognosis of gastrointestinal stromal tumors (GISTs). Therefore, we conducted a meta-analysis to determine the prognostic role of tumor necrosis in patients with GIST. METHODS PubMed, Embase, and Web of Science electronic databases were searched from their inception to March 2018. Studies reporting data on the relationship between tumor necrosis and GIST prognosis were eligible. The measure of the effect of interest was the odds ratios (ORs) with 95% confidence intervals (CIs). This study has been registered in the Prospero (number CRD42018096036). RESULTS In total, 18 studies including 2320 patients were identified. The total odds of tumor necrosis were associated with a poor GIST prognosis (OR = 5.54, 95% CI = 4.39-6.99). Subgroup analysis of different observed outcomes indicated that tumor necrosis was associated with a decreased disease-free survival (OR = 7.08, 95% CI = 4.78-10.49), recurrence-free survival (OR = 3.96, 95% CI = 2.48-6.32), and overall survival (OR = 4.29, 95% CI = 2.02-9.13). In addition, any tumor site, tumor size, follow-up time, ethnicity, different outcomes of GIST, and different degrees of positive staining of immunohistochemical markers subgroups showed a significantly increased risk of a poor prognosis. CONCLUSIONS Tumor necrosis may likely predict a poorer prognosis for GIST. However, further well-designed prospective studies with large sample size are required in the future.
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Affiliation(s)
| | - Lin Xia
- Department of Gastrointestinal Surgery
| | - Yan Zhou
- Department of Pathology, West China Hospital, Sichuan University
| | | | | | - Yi Chen
- Department of Gastrointestinal Surgery
| | - Rui Zhao
- Department of Gastrointestinal Surgery
| | | | - Liang Du
- Chinese Evidence-based Medicine/Cochrane Center, Chengdu, China
| | - Yong Zhou
- Department of Gastrointestinal Surgery
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Chen T, Ye LY, Feng XY, Qiu HB, Zhang P, Luo YX, Yuan LY, Chen XH, Hu YF, Liu H, Li Y, Tao KX, Yu J, Li GX. Performance of risk stratification systems for gastrointestinal stromal tumors: A multicenter study. World J Gastroenterol 2019; 25:1238-1247. [PMID: 30886506 PMCID: PMC6421238 DOI: 10.3748/wjg.v25.i10.1238] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 01/30/2019] [Accepted: 02/15/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor type in the gastrointestinal system. Presently, various classification systems to prognosticate GISTs have been proposed. AIM To evaluate the application value of four different risk stratification systems for GISTs. METHODS Patients who were diagnosed with GISTs and underwent surgical resection at four hospitals from 1998 to 2015 were identified from a database. Risk of recurrence was stratified by the modified National Institute of Health (NIH) criteria, the Armed Forces Institute of Pathology (AFIP) criteria, the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic nomogram, and the contour maps. Receiver operating characteristic (ROC) curves were established to compare the four abovementioned risk stratification systems based on the area under the curve (AUC). RESULTS A total of 1303 patients were included in the study. The mean age of the patients was 55.77 ± 13.70 yr; 52.3% of the patients were male. The mean follow-up period was 64.91 ± 35.79 mo. Approximately 67.0% the tumors were located in the stomach, and 59.5% were smaller than 5 cm; 67.3% of the patients had a mitotic count ≤ 5/50 high-power fields (HPFs). Thirty-four tumors ruptured before and during surgery. Univariate analysis demonstrated that tumor size > 5 cm (P < 0.05), mitotic count > 5/50 HPFs (P < 0.05), non-gastric location (P < 0.05), and tumor rupture (P < 0.05) were significantly associated with increased recurrence rates. According to the ROC curve, the AFIP criteria showed the largest AUC (0.754). CONCLUSION According to our data, the AFIP criteria were associated with a larger AUC than the NIH modified criteria, the MSKCC nomogram, and the contour maps, which might indicate that the AFIP criteria have better accuracy to support therapeutic decision-making for patients with GISTs.
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Affiliation(s)
- Tao Chen
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Liang-Ying Ye
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Xing-Yu Feng
- Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Hai-Bo Qiu
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, Guangdong Province, China
| | - Peng Zhang
- Department of General Surgery, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Yi-Xin Luo
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Li-Yi Yuan
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Xin-Hua Chen
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Yan-Feng Hu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Hao Liu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Yong Li
- Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Kai-Xiong Tao
- Department of General Surgery, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Jiang Yu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Guo-Xin Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
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Klieser E, Pichelstorfer M, Weyland D, Kemmerling R, Swierczynski S, Dinnewitzer A, Jäger T, Kiesslich T, Neureiter D, Illig R. Back to the start: Evaluation of prognostic markers in gastrointestinal stromal tumors. Mol Clin Oncol 2016; 4:763-773. [PMID: 27123276 DOI: 10.3892/mco.2016.819] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 02/26/2016] [Indexed: 12/29/2022] Open
Abstract
The aim of this study was to provide a standardized risk stratification model for gastrointestinal stromal tumors (GISTs) based on tumor localization, tumor size, involved lymph nodes and metastases, as well as mitotic activity and other morphological and molecular markers, in order to improve the risk evaluation scheme for recurrence, metastatic spread and survival for patients with GIST. A total of 201 cases of patients with GIST were investigated according to standardized morphological markers, including nuclear pleomorphism, tumor cell necrosis, mucosal infiltration, ulceration, skeinoid fibers and growth pattern. In addition, all cases were immunohistochemically analyzed using a tissue microarray platform for various markers of differentiation (CD34, CD44, CD117, desmin, discovered on GIST 1, platelet-derived growth factor receptor α, S-100 and smooth muscle actin) and proliferation (B-cell lymphoma 2, P16, P53, phosphohistone H3 and Ki-67). These findings were correlated by uni- and multivariable analyses with clinicopathological characteristics, including recurrence, metastasis and survival. The general clinicopathological parameters of this GIST specimen cohort were comparable to previous studies. While several parameters exhibited clear associations to each other and to the defined clinical endpoints, the multivariate analysis reduced the number of relevant prognostic variables to localization, margin status, growth pattern and hematoxylin and eosin-based mitosis/Ki-67-based proliferation of GISTs. With the exception of CD34, none of the applied markers of differentiation and proliferation were found to be independent prognostic markers in GIST and the classical risk factors of GIST remain important prognostic factors. Additionally, growth pattern may predict the risk of recurrence and metastasis in GIST patients. Additional independent molecular prognostic markers remain to be identified and validated.
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Affiliation(s)
- Eckhard Klieser
- Institute of Pathology, Paracelsus Medical University/Salzburg General Hospital (SALK), A-5020 Salzburg, Austria
| | - Maximilian Pichelstorfer
- Institute of Pathology, Paracelsus Medical University/Salzburg General Hospital (SALK), A-5020 Salzburg, Austria; Bio- and Environmental Technology Program, University of Applied Sciences Upper Austria, A-4600 Wels, Austria
| | - Denis Weyland
- Institute of Pathology, Paracelsus Medical University/Salzburg General Hospital (SALK), A-5020 Salzburg, Austria; Bio- and Environmental Technology Program, University of Applied Sciences Upper Austria, A-4600 Wels, Austria
| | - Ralf Kemmerling
- Institute of Pathology, Paracelsus Medical University/Salzburg General Hospital (SALK), A-5020 Salzburg, Austria
| | - Stefan Swierczynski
- Department of Surgery, Paracelsus Medical University/Salzburg General Hospital (SALK), A-5020 Salzburg, Austria
| | - Adam Dinnewitzer
- Department of Surgery, Paracelsus Medical University/Salzburg General Hospital (SALK), A-5020 Salzburg, Austria
| | - Tarkan Jäger
- Department of Surgery, Paracelsus Medical University/Salzburg General Hospital (SALK), A-5020 Salzburg, Austria
| | - Tobias Kiesslich
- Department of Internal Medicine I, Paracelsus Medical University/Salzburg General Hospital (SALK), A-5020 Salzburg, Austria; Laboratory for Tumor Biology and Experimental Therapies (TREAT), Institute of Physiology and Pathophysiology, Paracelsus Medical University, A-5020 Salzburg, Austria
| | - Daniel Neureiter
- Institute of Pathology, Paracelsus Medical University/Salzburg General Hospital (SALK), A-5020 Salzburg, Austria
| | - Romana Illig
- Institute of Pathology, Paracelsus Medical University/Salzburg General Hospital (SALK), A-5020 Salzburg, Austria
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Ki67 as a prognostic factor for long-term outcome following surgery in gastrointestinal stromal tumors. Eur J Gastroenterol Hepatol 2015; 27:1276-80. [PMID: 26275084 DOI: 10.1097/meg.0000000000000454] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVE This study aimed to examine the value of Ki67 expression along with other potential prognostic factors for predicting overall survival and disease-free survival in patients with gastrointestinal stromal tumors who underwent curative resection. PATIENTS AND METHODS Sixty-eight histologically confirmed and operated patients with gastrointestinal stromal tumors were included. Clinical and follow-up data were retrieved from medical records and patients were contacted at the end of the study. The effects of certain clinical and histopathological parameters on survival outcomes were examined. RESULTS Sixty-eight patients were followed for a mean duration of follow-up of 2923.3 patient-months. Twelve deaths (17.6%), seven metastasis (10.3%), and two local recurrences (2.9%) occurred. Overall survival was 102.5 months [95% confidence interval (CI), 88.3-116.8] and disease-free survival was 91.8 months (95% CI, 76.5-107.2). Multivariate analyses identified a high Ki67 index (≥ 10%) as an independent predictor of both poor overall survival (hazard ratio, 4.8; 95% CI 1.2-19.2; P=0.027) and poor disease-free survival (hazard ratio, 15.3; 95% CI, 4.7-50.2). CONCLUSION A high Ki67 expression seems to be a useful prognostic factor that would aid in predicting disease course in gastrointestinal stromal tumors. These findings deserve further investigation in larger studies.
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Zhang Q, Shou CH, Yu JR, Yang WL, Liu XS, Yu H, Gao Y, Shen QY, Zhao ZC. Prognostic characteristics of duodenal gastrointestinal stromal tumours. Br J Surg 2015; 102:959-64. [PMID: 25980461 PMCID: PMC4682471 DOI: 10.1002/bjs.9831] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2014] [Revised: 02/25/2015] [Accepted: 03/17/2015] [Indexed: 01/10/2023]
Abstract
Background This study evaluated the clinical characteristics, surgical procedures and prognosis of duodenal gastrointestinal stromal tumours (GISTs). Methods Patients with a diagnosis of primary duodenal GIST treated between January 2000 and December 2012 were analysed. Patients with gastric and small intestinal GISTs were chosen as control groups according to the following parameters: age, tumour size, mitotic index and adjuvant imatinib therapy. Operative procedures for patients with duodenal GIST included pancreaticoduodenectomy or limited resection. Disease-free survival (DFS) was calculated using Kaplan–Meier analysis. Results Some 71 patients with duodenal, 71 with gastric and 70 with small intestinal GISTs were included in the study. DFS of patients with duodenal GIST was shorter than that of patients with gastric GIST (3-year DFS 84 versus 94 per cent; hazard ratio (HR) 3.67, 95 per cent c.i. 1.21 to 11.16; P = 0.014), but was similar to that of patients with small intestinal GIST (3-year DFS 84 versus 81 per cent; HR 0.75, 0.37 to 1.51; P = 0.491). Patients who underwent pancreaticoduodenectomy were older, and had larger tumours and a higher mitotic index than patients who had limited resection. The 3-year DFS was 93 per cent among patients who had limited resection compared with 64 per cent for those who underwent PD (HR 0.18, 0.06 to 0.59; P = 0.001). Conclusion The prognosis of duodenal GISTs is similar to that of small intestinal GISTs. Prognosis no different than for small bowel gastrointestinal stromal tumours
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Affiliation(s)
- Q Zhang
- Department of Gastrointestinal Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China
| | - C-H Shou
- Department of Gastrointestinal Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China
| | - J-R Yu
- Department of Gastrointestinal Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China
| | - W-L Yang
- Department of Gastrointestinal Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China
| | - X-S Liu
- Department of Gastrointestinal Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China
| | - H Yu
- Department of Gastrointestinal Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China
| | - Y Gao
- Department of Gastrointestinal Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China
| | - Q-Y Shen
- Department of Gastrointestinal Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China
| | - Z-C Zhao
- Department of Gastrointestinal Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China
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