Recent classifications systems for gastroenteropancreatic neuroendocrine tumors A single-center experience (original) (raw)
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European Journal of Gastroenterology & Hepatology, 2016
Aim This study aimed to determine the degree of concordance between TNM staging used in the determination of the prognosis of gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients and the Ki-67 proliferation index value used in the grading of these tumors and investigate the most reliable prognostic parameter among them. Materials and methods The medical files of the patients with GEP-NET who were diagnosed or followed up in Erciyes University Faculty of Medicine were retrospectively examined and demographic characteristics, survival times, grade of these tumors, histopathologically detected Ki-67 values, and histopathological characteristics were recorded and evaluated statistically. Results The mean age (53.09 ± 14.6 years; range, 16-85 years) of all (n = 141) the patients was estimated. The patient population included 72 (51.1%) female and 69 (48.9%) male patients, with a male/female ratio of 0.95. The most frequently encountered primary sites were the stomach (33.3%), and then in decreasing oder of frequency the pancreas (27%), colonrectum (15.6%), the small intestine (12.8%), and the appendix (11.3%). The GEP-NET of the patients was in grade 1 (G1) (n: 103; 73%), grade 2 (G2) (n: 24; 17%), and grade 3 (G3) (n: 14; 10%). The GEP-NET of the patients was stage I (n: 66; 46.8%), stage II (n: 14; 9.9%), stage III (n: 12; 8.5%), and stage IV (n: 49; 34.8%). In the statistical analysis, Ki-67 increased in parallel with the stage of the disease (P < 0.001). As Ki-67 increased at a rate of 1%, survival rates of the patients decreased 1.027 times (P = 0.01). Five-year survival rates of the patients were 88% in G1, 44% in G2, and 24% in G3. Patients in G2 and G3 had a 6.67 and 12.38 times lower chance of survival compared with G1 patients, respectively. Survival rates of stage IV patients were 5.6 times lower relative to stages I and II patients, respectively (P < 0.001). The median 5-year survival rates of the patients were 90% in stage I, 100% in stage II, 47% in stage III, and 46% in stage IV. In univariate analysis, age of the patients, grade, stage of the tumor, and lymph node metastases were found to be parameters that affected overall survival, whereas no significant correlation was found between the sex of the patient and the primary organ from which the tumor originated and survival rates. However, in the multivariate analysis, survival rates decreased inversely with age, whereas no significant correlation was found between grade and stage of the tumor and survival rates. Conclusion In conclusion, a decrease in the average survival rate in parallel with an increase in the grade of the tumor was more prominent compared with a decrease in survival rates in accordance with an increase in the stage of the tumor. This indicates that in the prediction of prognosis in patients with GEP-NET, the Ki-67 value can be a more important evaluation factor relative to staging.
Annals of Diagnostic Pathology, 2015
between 2000 and 2012 were retrieved and reevaluated. Demographic features of the groups were analyzed from the institutional database. Only resection materials were included in the study. Biopsies and metastatic materials were excluded. 2.2. Immunohistochemical Analysis Immunohistochemical analysis of Chromogranin A (LK2H10+ PHE5, Neomarkers), Synaptophysin (27G12, Novacastra), and Neuron-Specific Enolase (Clone E 27, Neomarkers) was used to evaluate for neuroendocrine differentiation. All the cases were diffusely (>%50) and strongly positive for at least two neuroendocrine markers. Ki67 (RM-9106-R7, Neomarkers) immunostaining was performed for the proliferation index. One representative block was selected for Ki-67 index. 2.3. Classification, Grading and Staging The tumors are classified as WDETB, WDETUB,WDEC or PDEC according to the WHO 2000/2004 guidelines. Tumor diameter, localization, depth of invasion (gross local invasion for pancreas) and metastatic state are considered in this classification (Table 1, Table 2, Table 3). All the slides were re-reviewed for prognostic parameters such as angiolymphatic invasion, perineural invasion, necrosis, mitosis; blinded of the original diagnosis. Mitotic count and the ki-67 index were investigated for classifying the cases according to WHO 2010. Counting Ki-67 and mitosis were performed blinded by two pathologists. The mitotic index was expressed as the number of mitoses per 10 HPF (approximately 2 mm²) after evaluating at least 50 HPF (or the entire tumor area in case of small tumors). Proliferation zone cells
Neuroendocrinology, 2016
used to assess the prognostic significance of various clinical and histopathologic features. Results: With a median followup of 81 months, the median OS was 12.9 months. At multivariate analysis, morphological differentiation, Ki-67 index, MMRd, stage, and CD117 expression were independent prognostic markers in NECs. Three different prognostic categories of NECs were identified according to the degree of morphologic differentiation (well vs. poorly differentiated) and Ki-67 index (<55% vs. ≥ 55%). On this basis, median OS was 43.6 months in well-differentiated neoplasms with a Ki-67 index 20-55% (named type A), 24.5 months in poorly differentiated neoplasms with a Ki-67 index 20-55% (type B), and 5.3 months (p < 0.0001) in poorly differentiated neoplasms with a Ki-67 index ≥ 55% (type C). Conclusions: The present study suggests that GEP-NECs represent a heterogeneous group of neoplasms which can be better classified in different prognostic categories using both tumor morphology and Ki-67 index.
Endokrynologia Polska, 2022
This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially Guidelines Beata Kos-Kudła et al. Guidelines persons/year, with the primary lesion most frequently found in the small intestine (37.4%). Since 2000, rectal NENs have been diagnosed more frequently than small intestine NENs [2, 6-8]. The incidence of GEP-NETs in the USA, based on SEER data, was 3.56/100,000 persons/year. In Europe, the incidence of GEP-NETs is also increasing-from 1.33 to 2.33/100,000 persons/year; however, these data come from different registries and are mainly retrospective. Higher incidence is observed among men (5.35/100,000 persons/year) compared to women (4.76/100,000 persons/year) [1, 5-7]. The vast majority of NENs are sporadic, well-differentiated tumours. However, GEP-NETs originating from the pancreas, duodenum, stomach, and much less frequently, from the thymus and lungs sometimes constitute an element of multiple endocrine neoplasia type 1 (MEN-1) syndrome. Pancreatic neuroendocrine tumours (PanNETs) may also be associated with von Hippel-Lindau (VHL) syndrome, tuberous sclerosis complex (TSC), and neurofibromatosis (NF). In these congenital diseases, NETs can be multifocal and occur 10-20 years earlier than in sporadic cases. The frequency of the hereditary causes (MEN-1, VHL) is estimated at about 5%. Genome studies revealed the presence of germline mutations in, e.g., MUTYH, CHEK2, and BRCA2 and a propensity to PanNETs in approximately 17% of the studied population [1]. 2. Diagnostics 2.1. Biochemical diagnostics Biochemical diagnostics of NENs involves the following: A. Non-specific markers The most frequently used diagnostic method is determination of the chromogranin A (CgA) concentration in the serum (less frequently in the plasma) [1, 8, 9]. CgA is a relatively stable protein in blood. However, there are two different methods for determining the concentration of CgA: radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) in Neuroendocrine neoplasms (NENs) arise from the disseminated system of neuroendocrine cells and can occur in various parts of the body. However, they are most often found in the gastrointestinal tract and lungs. The term NENs includes both well-differentiated neuroendocrine tumours and neuroendocrine carcinomas (NECs), which account for 10-20% of all NENs. The following characteristics of NENs should be considered in the diagnostic and therapeutic process: proliferative activity, presence of somatostatin receptors (SSTRs), tumour growth rate, and extent of the neoplastic disease [1]. in the prevalence of GEP-NENs. Local and regional NENs are diagnosed more frequently than those with distant metastases. The detectability of NENs is increasing, e.g. from 1973 to 2004 the incidence of NENs increased from 2.1 to 5.25 new cases per 100,000
Factors Affecting Survival in Neuroendocrine Tumors: A 15-Year Single Center Experience
Asian Pacific Journal of Cancer Prevention
Background: Neuroendocrine tumors are a heterogeneous group of tumors that can originate from all of the neuroendocrine cells in the body, mostly from the gastrointestinal tract. In addition to early diagnosis, streaming patients into appropriate prognostic groups is an important component of treatment. In this study, we examined the factors that affect survival in patients we followed in our center between 2000-2016. Methods: The demographic data, clinical and pathological features of patients were obtained from their medical files. TNM staging and tumor grading were performed according to AJCC and WHO 2010 classification. SPSS 15.0 for Windows programme was used for statistical analysis. Results: 85 patients (32 male, 53 female) were included into the study. The median age of the patients was 55,7 (27-83) years. Eighty percent of the tumors were of gastroenteropancreatic system, most commonly stomach (27.1%) origin. Nineteen patients (22.4%) died during follow-up. In univariate analysis; age (p<0,001), stage (p=0.002), primary tumor localization (p=0.005), grade (p<0.001), Ki-67 value (p<0.001), number of metastases (p=0.001) and type of surgery (p<0.001) were found to be factors affecting survival. Age (p=0.024) and Ki67 (p <0.001) were the independent prognostic factors for survival in multivariate analysis. For the cutoff value of 6%, Ki-67 had a sensitivity of 83.3% and specifity of 71.4% for survival determination. Conclusion: Ki-67 ratio and age were the most important factors affecting survival in neuroendocrine tumors in our study. Ki-67 ratio has a high sensitivity and specificity for predicting survival, a cutoff value of 6% may be used to predict survival.
Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms
Cancers, 2022
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of malignancies that originate from the diffuse neuroendocrine cell system of the pancreas and gastrointestinal tract and have increasingly increased in number over the decades. GEP-NENs are roughly classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas; it is essential to understand the pathological classification according to the mitotic count and Ki67 proliferation index. In addition, with the advent of molecular-targeted drugs and somatostatin analogs and advances in endoscopic and surgical treatments, the multidisciplinary treatment of GEP-NENs has made great progress. In the management of GEP-NENs, accurate diagnosis is key for the proper selection among these diversified treatment methods. The evaluation of hormone-producing ability, diagnostic imaging, and histological diagnosis is central. Advances in the study of the genetic landscape ...
The journal of Tepecik Education and Research Hospital, 2021
Objective: Neuroendocrine neoplasms (NEN) are frequently located in the lung and gastroenteropancreatic (GEP) system organs. Neuroendocrine carcinoma (NEC) constitutes 5% of GEP NENs and has a very high malignancy potential. In this study, it is aimed to determine a new threshold value in addition to the 20% Ki-67 proliferation index that was specified as a threshold value for predicting survival in patients with grade (G) 3 tumors according to World Health Organization (WHO) 2010 classification. Method: Demographic, clinicopathologic features and survival rates of 34 patients diagnosed with GEP NEC between 2008-2015 in İzmir Katip Celebi University Atatürk Training and Research Hospital Medical Pathology Clinic were evaluated retrospectively. Results: Most of the 34 (76.5%) cases were male and the average age was 63.9 years. Median survival rates were 15, and 7 months in patients with Ki-67 indexes of ≤65% and >65%, respectively (p=0.232). Conclusion: Recent studies have shown h...
The Turkish Journal of Gastroenterology, 2015
Background/Aims: Gastrointestinal and pancreatic neuroendocrine tumors (GEPNETs) originate from the cells of the endocrine system. Their molecular genetic mechanism of development and progression is complex and remains largely unknown. The purpose of this study was to review the gastrointestinal and pancreatic neuroendocrine tumors and to evaluate p53, Ki-67 and CD 117 expressions with their clinicopathological correlations. Materials and Methods: Twenty-one patients were reviewed and classified as having well-differentiated neuroendocrine neoplasm (WDET, Grade I), well-differentiated neuroendocrine carcinoma (WDEC, Grade II) and poorly differentiated neuroendocrine carcinoma (PDEC, Grade III). We performed immunohistochemical tests to characterize the expession of the immunoreactivity for synaptophysin, chromogranin, p53, Ki67 and CD 117. Results: Median age of 21 patients was 43 years. Thirteen (61.9%) patients were male and eight (38.1%) patients were female. Tumors were located in the stomach (38.1%), appendix (38.1%), duodenum (4.8%), ileum (4.8%), colon (9.5%), and pancreas (4.8%). Conclusion: There was a statistically significant difference between well-differentiated endocrine neoplasm (Grade I), and well-differentiated endocrine carcinoma (WDEC, Grade II) and PDEC for Ki-67 >20% (p<0.001) (Pearson chisquare test). There was a statistically significant difference between WDET (Grade I), WDEC (Grade II) and PDEC (Grade III) for p53 positivity (p<0.05) (Pearson chi-square test).