Evaluation of Ki-67 index in EUS–FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors

Hasegawa, Toshiyuki; Yamao, Kenji; Hijioka, Susumu; Bhatia, Vikram; Mizuno, Nobumasa; Hara, Kazuo; Imaoka, Hiroshi; Niwa, Yasumasa; Tajika, Masahiro; Kondo, Shinya; Tanaka, T; Shimizu, Yasuhiro; Kinoshita, Taira; Kohsaki, Takuhiro; Nishimori, Isao; Iwasaki, Shinji; Saibara, Toshiji; Hosoda, Waki; Yatabe, Yasushi

doi:10.1055/s-0033-1344958

Cited by 122 publications

(168 citation statements)

References 27 publications

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“…Similar observations were made by Hasegawa et al, who showed that majority of volume of G2 tumours was in fact composed of G1 areas [12].…”

Section: Ki67 LI Heterogeneity In the Context Of Cssupporting

confidence: 89%

“…As mentioned above, Hasegawa et al documented that NET G2 consist in majority from G1 areas [12]. Goodell et al distinguished 3 groups of pancreatic NET based on Ki67 LI in a single-field HS and 10 consecutive fields average: 13/45 (28.9%) and 6/45 (13.3%) were scored as G1 and G2 based on both scoring techniques (respectively), but as many as 26/45 (57.8%) were scored as G2 based on a single HS, but as G1 based on 10 consecutive fields average [24].…”

Section: Ki67 LI Heterogeneity Beyond Single Hs or Csmentioning

confidence: 87%

“…(11) All NEC cases were diagnosed as G3 irrespective of number of examined cells and HS selected for counting. (12) In adequately preserved samples of NEC, Ki67 LI in CS was high enough to establish G3 grade. (13) WHO and ENETS scoring criteria were not sufficiently detailed to ensure reliable reporting of grade in a subset of pancreatic NEN.…”

Section: Discussionmentioning

confidence: 99%

“…Ki67 LI heterogeneity was observed not only within primary tumour tissue [9,10,11,12], but also between primary and metastatic lesions [13,14,15] and within and between metastases [16,17].…”

Section: Introductionmentioning

confidence: 97%

“…Some investigators showed that grading of pancreatic NEN in cytological samples was less reliable (i.e. showed lower percentage of agreement with reference grade established in subsequent resection specimens) if number of examined cells was small [12,32].…”

Section: Introductionmentioning

confidence: 99%

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Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Liszka¹

2016

pjp

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Reporting of Ki67 labeling index (LI) is a routine in diagnostics of neuroendocrine neoplasms of the pancreas. The aim of the study was to examine whether heterogeneity of Ki67 LI distribution in primary tumoral tissue influences precision of reporting of Ki67 LI and Ki67-LI-based grade, both established in adherence to WHO 2010 guidelines. Seventy-one samples of neuroendocrine tumours (NET) and 6 samples of neuroendocrine carcinomas (NEC) of the pancreas were taken for manual counting of Ki67 LI in 25 portions of 100 cells (2500 cells in total) in 3 hot spots an in a single area of lower proliferation rate (cold spot) in each case. Both NET and NEC showed Ki67 LI heterogeneity within primary tumour. Almost 20% of NET showed higher grade when 500 cells rather than 2000 cells were counted in hot spot area. Suboptimal choice of hot spot resulted in under-grading of approximately 20% of NET. Cold spots were constantly present in NET. Heterogeneity of Ki67 LI was also present in NEC, but it virtually never resulted in under-grading. Concept and methodology of Ki67 LI counting in neuroendocrine neoplasms of the pancreas requires clarification. Efforts aiming to improve precision of assessment of Ki67 LI are needed.

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“…Similar observations were made by Hasegawa et al, who showed that majority of volume of G2 tumours was in fact composed of G1 areas [12].…”

Section: Ki67 LI Heterogeneity In the Context Of Cssupporting

confidence: 89%

Section: Ki67 LI Heterogeneity Beyond Single Hs or Csmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Liszka¹

2016

pjp

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Evaluation of Survival Following Surgical Resection for Small Nonfunctional Pancreatic Neuroendocrine Tumors

et al. 2023

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ImportanceThe number of patients with small nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is increasing. However, the role of surgery for small NF-PanNETs remains unclear.ObjectiveTo evaluate the association between surgical resection for NF-PanNETs measuring 2 cm or smaller and survival.Design, Setting, and ParticipantsThis cohort study used data from the National Cancer Database and included patients with NF-pancreatic neuroendocrine neoplasms who were diagnosed between January 1, 2004, and December 31, 2017. Patients with small NF-PanNETs were divided into 2 groups: group 1a (tumor size, ≤1 cm) and group 1b (tumor size, 1.1-2.0 cm). Patients without information on tumor size, overall survival, and surgical resection were excluded. Data analysis was performed in June 2022.ExposuresPatients with vs without surgical resection.Main Outcomes and MeasuresThe primary outcome was overall survival of patients in group 1a or group 1b who underwent surgical resection compared with those who did not, which was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Interactions between preoperative factors and surgical resection were analyzed with a multivariable Cox proportional hazards regression model.ResultsOf the 10 504 patients with localized NF-PanNETs identified, 4641 were analyzed. These patients had a mean (SD) age of 60.5 (12.7) years and included 2338 males (50.4%). The median (IQR) follow-up time was 47.1 (28.2-71.6) months. In total, 1278 patients were in group 1a and 3363 patients were in group 1b. The surgical resection rates were 82.0% in group 1a and 87.0% in group 1b. After adjustment for preoperative factors, surgical resection was associated with longer survival for patients in group 1b (hazard ratio [HR], 0.58; 95% CI, 0.42-0.80; P &lt; .001) but not for patients in group 1a (HR, 0.68; 95% CI, 0.41-1.11; P = .12). In group 1b, interaction analysis found that age of 64 years or younger, absence of comorbidities, treatment at academic institutions, and distal pancreatic tumors were factors associated with increased survival after surgical resection.Conclusions and RelevanceFindings of this study support an association between surgical resection and increased survival in select patients with NF-PanNETs measuring 1.1 to 2.0 cm who were younger than 65 years, had no comorbidities, received treatment at academic institutions, and had tumors of the distal pancreas. Future investigations of surgical resection for small NF-PanNETs that include the Ki-67 index are warranted to validate these findings.

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Prognostic impact of Ki‐67 proliferative index in resectable pancreatic ductal adenocarcinoma

et al. 2019

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BackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by complex biological features and poor prognosis. A prognostic stratification of PDAC would help to improve patient management. The aim of this study was to analyse the expression of Ki‐67 in relation to prognosis in a cohort of patients with PDAC who had surgical treatment.MethodsPatients who had pancreatic resection between August 2010 and October 2014 for PDAC at two Italian centres were reviewed retrospectively. Patients with metastatic or locally advanced disease, those who received neoadjuvant chemotherapy, patients with PDAC arising from intraductal papillary mucinous neoplasm and those with missing data were excluded. Clinical and pathological data were retrieved and analysed. Ki‐67 expression was evaluated using immunohistochemistry and patients were stratified into three subgroups. Survival analyses were performed for disease‐free (DFS) and disease‐specific (DSS) survival outcomes according to Ki‐67 expression and tumour grading.ResultsA total of 170 patients met the selection criteria. Ki‐67 expression of 10 per cent or less, 11–50 per cent and more than 50 per cent significantly correlated with DFS and DSS outcomes (P = 0·016 and P = 0·002 respectively). Ki‐67 index was an independent predictor of poor DFS (hazard ratio (HR) 0·52, 95 per cent c.i. 0·29 to 0·91; P = 0·022) and DSS (HR 0·53, 0·31 to 0·91; P = 0·022). Moreover, Ki‐67 index correlated strongly with tumour grade (P < 0·001). Patients with PDAC classified as a G3 tumour with a Ki‐67 index above 50 per cent had poor survival outcomes compared with other patients (P < 0·001 for both DFS and DSS).ConclusionKi‐67 index could be of use in predicting the survival of patients with PDAC. Further investigation in larger cohorts is needed to validate these results.

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Evaluation of Ki-67 index in EUS–FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors

Abstract: Grading of PNETs by the highest Ki-67 index in EUS-FNA specimens with adequate cellularity has a high concordance with grading of resected specimens, and can predict long term patient survival with high accuracy.

Cited by 122 publications

References 27 publications

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Evaluation of Survival Following Surgical Resection for Small Nonfunctional Pancreatic Neuroendocrine Tumors

Prognostic impact of Ki‐67 proliferative index in resectable pancreatic ductal adenocarcinoma

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