Role of Ki‐67 Proliferation Index in the Assessment of Patients with Neuroendocrine Neoplasias Regarding the Stage of Disease

Miller, H.; Drymousis, Panagiotis; Flora, Rashpal; Goldin, Robert; Spalding, Duncan; Frilling, Andrea

doi:10.1007/s00268-014-2451-0

Cited by 79 publications

(71 citation statements)

References 66 publications

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“…Previous researches have indicated that higher Ki-67 index showed worse prognosis in GEP-NENs [28,29]. Some studies with small sample sizes of colorectal NENs also presented similar results.…”

Section: Discussionsupporting

confidence: 70%

Clinicopathological features and prognostic factors of colorectal neuroendocrine neoplasms.

Jiang

Yuan

2017

JCO

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Background. Limited research is available regarding colorectal NENs and the prognostic factors remain controversial. Materials and Methods. A total of 68 patients with colorectal NENs were studied retrospectively. Clinical characteristics and prognosis between colonic and rectal NENs were compared. The Cox regression models were used to evaluate the predictive capacity. Results. Of the 68 colorectal NENs patients, 43 (63.2%) had rectal NENs, and 25 (36.8%) had colonic NENs. Compared with rectal NENs, colonic NENs more frequently exhibited larger tumor size ( < 0.0001) and distant metastasis ( < 0.0001). Colonic NENs had a worse prognosis ( = 0.027), with 5-year overall survival rates of 66.7% versus 88.1%. NET, NEC, and MANEC were noted in 61.8%, 23.5%, and 14.7% of patients, respectively. Multivariate analyses revealed that tumor location was not an independent prognostic factor ( = 0.081), but tumor size ( = 0.037) and pathological classification ( = 0.012) were independent prognostic factors. Conclusion. Significant differences exist between colonic and rectal NENs. Multivariate analysis indicated that tumor size and pathological classification were associated with prognosis. Tumor location was not an independent factor. The worse outcome of colonic NENs observed in clinical practice might be due not only to the biological differences, but also to larger tumor size in colonic NENs caused by the delayed diagnosis.

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Section: Discussionsupporting

confidence: 70%

Clinicopathological features and prognostic factors of colorectal neuroendocrine neoplasms.

Jiang

Yuan

2017

JCO

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“…Most SBNETs are low-grade lesions; nevertheless, up to 90% of patients with SBNET have lymph node metastases, and in 45-70% of cases, liver metastases are present at the initial diagnosis , Norlén et al 2012, Miller et al 2014. These intriguing characteristics contribute to a 5-year survival of less than 60% from diagnosis of liver metastases (Ahmed et al 2009) compared to about 80% in patients with loco-regionally limited disease (Norlén et al 2012).…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

Miller¹,

Frampton²,

Malczewska³

et al. 2016

Endocrine-Related Cancer

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Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed (n = 90), including primary SBNETs (n = 28), adjacent normal small bowel (NSB; n = 14), matched lymph node (LN) metastases (n = 24), normal LNs (n = 7), normal liver (n = 2) and liver metastases (n = 15). We then evaluated potentially targeted genes by performing integrated computational analyses. We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA-mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted.

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“…Liver metastasis has been reported in more than 50% of cases of PanNET [39], and the elevation of the Ki-67 index in primary tumors increases the probability of metastasis [40]. The Ki-67 index or tumor grade is higher for liver metastatic sites than primary sites [40,41]; however, there are no reports examining the mutational status of both primary and metastatic sites. In our analysis of three PanNET patients with liver metastasis, all three metastatic site had a newly developed mutation, which was not detected in the primary site, and two of three cases had an advanced grade in the metastatic site than in the primary site.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Cancer-related Genes Associated with Grading of Well Differentiated Pancreatic Neuroendocrine Neoplasms

Yokota¹,

Fukasawa²,

Takano³

et al. 2017

Pancreat Disord Ther

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Objectives: Although recent advances in next-generation sequencing (NGS) have revealed some genetic alterations in various tumors, including pancreatic neuroendocrine tumors (PanNETs), their clinical significance is not fully understood. To investigate the clinical significance of gene alteration in PanNETs, we performed genetic analysis of well differentiated PanNETs using NGS.Methods: Twenty-nine resected primary PanNET tissue samples and three samples of metastatic liver tissues, obtained from 29 PanNET patients, were analyzed. DNA was extracted from laser-captured formalin-fixed paraffinembedded tissues, and 50 cancer-associated genes, including approximately 2,800 hotspots, were amplified by multiplex PCR. Amplified libraries were sequenced using NGS, and the results were analyzed in conjunction with respective clinicopathological features. Results:Among 50 investigated genes, somatic mutations were observed in four of 29 PanNET cases. We identified APC mutations in three cases, PTEN in two, and VHL and STK11 in one. The identified mutations were observed only in NET G2 tumors. All liver metastases contained at least one mutation, such as PTEN or TP53, which was not observed in the primary tumor. Conclusion:The cancer-related gene mutations observed in PanNETs were associated with G2 grade tumors. The mutations were more frequent in PanNET liver metastasis than in the primary tumors. Our analysis of liver metastasis cases suggested that cancer-related gene mutations might raise the tumor grade and promote liver metastasis. Further studies of associations between genetic alterations and clinicopathological features should help in the cancer diagnosis and prediction of therapeutic effects of molecular-target drugs.

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Role of Ki‐67 Proliferation Index in the Assessment of Patients with Neuroendocrine Neoplasias Regarding the Stage of Disease

Cited by 79 publications

References 66 publications

Clinicopathological features and prognostic factors of colorectal neuroendocrine neoplasms.

Clinicopathological features and prognostic factors of colorectal neuroendocrine neoplasms.

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

Alterations in Cancer-related Genes Associated with Grading of Well Differentiated Pancreatic Neuroendocrine Neoplasms

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