WHO 2004 Criteria and CK19 are Reliable Prognostic Markers in Pancreatic Endocrine Tumors

Schmitt, Anja; Anlauf, Martin; Rousson, Valentin; Schmid, Sonja; Kofler, Andreas; Riniker, Florian; Bauersfeld, Juliane; Barghorn, André; Probst‐Hensch, Nicole; Moch, Holger; Heitz, Philipp U.; Kloeppel, Guenter; Komminoth, Paul; Perren, Aurel

doi:10.1097/pas.0b013e31805f675d

Cited by 128 publications

(99 citation statements)

References 19 publications

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“…These data are in accordance with the data of Deshpande et al (2004) and a recent study by Schmitt et al (2007), investigating large series of EPTs, including different subtypes. Our data in this study, however, strongly indicate that CK19 expression is a suboptimal marker for poor tumorfree survival in insulinomas.…”

Section: Y M H Jonkers Et Al: Predictors Of Survival In Eptssupporting

confidence: 80%

DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients

Jonkers¹,

Claessen²,

Perren³

et al. 2007

Endocr Relat Cancer

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The clinical behavior of endocrine pancreatic tumors (EPTs) is difficult to predict in the absence of metastases or invasion to adjacent organs. Several markers have been indicated as potential predictors of metastatic disease, such as tumor size R2 cm, Ki67 proliferative index R2%, cytokeratin (CK) 19 status, and recently in insulinomas, chromosomal instability (CIN). The goal of this study was to evaluate the value of these markers, and in particular of the CIN, to predict tumor recurrence or progression and tumor-specific death, using a series of 47 insulinomas and 24 noninsulinoma EPTs. From these EPT cases, a genomic profile has been generated and follow-up data have been obtained. The proliferative index has been determined in 68 tumors and a CK19 expression pattern in 50 tumors. Results are statistically analyzed using Kaplan-Meier plots and the log-rank statistic. General CIN, as well as specific chromosomal alterations such as 3p and 6q loss and 12q gain, turned out to be the most powerful indicators for poor tumor-free survival (P%0.0004) and tumor-specific death (P%0.0113) in insulinomas. The CIN, chromosome 7q gain, and a proliferative index R2% were reliable in predicting a poor tumor-free survival in noninsulinoma EPTs (P%0.0181, whereas CK19 expression was the most optimal predictor of tumorspecific death in these tumors. In conclusion, DNA copy number status is the most sensitive and efficient marker of adverse clinical outcome in insulinomas and of potential interest in noninsulinoma EPTs. As a consequence, this marker should be considered as a prognosticator to improve clinical diagnosis, most practically as a simple multi-target test.

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Section: Y M H Jonkers Et Al: Predictors Of Survival In Eptssupporting

confidence: 80%

DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients

Jonkers¹,

Claessen²,

Perren³

et al. 2007

Endocr Relat Cancer

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“…In primary PETs, necrosis is a useful parameter for high-grade cancers but is a rare finding in low-grade tumors. 22,23 Since five of 12 (42%) benign insulinomas were positive for CC-3 whereas one malignant insulinoma and 19 of 23 (87%) potentially malignant primary non-β-cell PETs were negative for CC-3, CC-3 negative immunostaining may serve as a possible malignant marker in all PETs.…”

Section: Methodsmentioning

confidence: 99%

“…7 Pancreatic islets are an essential and special organ for sustaining life by regulating blood glucose levels through paracrine secretion of insulin, glucagon, somatostatin, pancreatic polypeptide and amylin, 22,23 and also through many other mechanisms, that tightly regulate blood glucose, the major fuel of the body. 24 The preliminary study with intestinal carcinoids for CC-3 staining revealed negative staining in carcinoids, which makes a phenotypic difference between benign PETs and intestinal carcinoids, also supporting potential malignancy of intestinal carcinoids (unpublished data).…”

Section: Methodsmentioning

confidence: 99%

Cleaved caspase-3 immunocytochemical staining for pancreatic islets and pancreatic endocrine tumors: A potential marker for biological malignancy

Tomita¹

2010

Islets

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“…In patients who cannot profit from surgery, the discrimination between well-differentiated endocrine tumor and well-differentiated endocrine carcinoma is based on the clinical and radiological documentation of locally aggressive or metastatic disease. 13,14 As under the term well-differentiated endocrine carcinoma are grouped cancers with variable behavior, there is the need of additional tools to distinguish prognostic classes particularly within this WHO category.…”

mentioning

confidence: 99%

Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients

et al. 2010

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Pancreatic endocrine tumors are rare diseases and devising a clinically effective prognostic stratification of patients is a major clinical challenge. This study aimed at assessing whether the tumor-node-metastasis (TNM)-based staging and proliferative activity-based grading recently proposed by the European NeuroEndocrine Tumors Society (ENETS) have clinical value. TNM was applied to 274 patients with histologically diagnosed pancreatic endocrine tumors operated from 1991 to 2005, with last follow-up at December 2007. According to World Health Organization (WHO) classification, 246 were well-differentiated neoplasms (51 benign, 56 uncertain behavior, 139 carcinomas) and 28 poorly differentiated carcinomas. Grading was based on Ki67 immunohistochemistry. Survival analysis not only ascertained the prognostic value of the TNM system but also highlighted that in the absence of nodal and distant metastasis, infiltration and tumor dimensions over 4 cm had prognostic significance. T parameters were then appropriately modified to reflect this weakness. The 5-year survival for modified TNM stages I, II, III and IV were 100, 93, 65 and 35%, respectively. Multivariate analysis identified TNM stages as independent predictors of death, in which stages II, III and IV showed a risk of death of 7, 29 and 58 times higher than stage I tumors (Po0.0001). Ki67-based grading resulted an independent predictor of survival with cut-offs at 5 and 20%. In conclusion, WHO classification assigns clinically significant diagnostic categories to pancreatic endocrine tumors that need prognostic stratification by applying a staging system. The ENETS-TNM provides the best option, but it requires some modifications to be fully functional. The modified TNM described in this study ameliorates the clinical applicability and prediction of outcome of the ENETS-TNM; it (i) assigns a risk of death proportional to the stage at the time of diagnosis, and (ii) allows a clinically based staging of patients, as the T parameters as modified permit their clinical-radiological recognition. Ki67-based grading discerns prognosis of patients with same stage diseases. Modern Pathology (2010) 23, 824-833; doi:10.1038/modpathol.2010 published online 19 March 2010 Keywords: pancreas; tumors; endocrine; staging; TNM; grading; prognosis Pancreatic endocrine tumors are rare and clinically taxing diseases, as their natural history is largely unknown. 1-4 Affected patients seek medical assistance due to symptoms resulting from either hormonal hypersecretion or mass. Thus, pancreatic endocrine tumors are clinically defined as functioning or nonfunctioning depending on the presence of a syndrome related to inappropriate hormone secretion. Such distinction, however, does not provide prognostic information. Pancreatic endocrine tumors are histologically divided into well-

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WHO 2004 Criteria and CK19 are Reliable Prognostic Markers in Pancreatic Endocrine Tumors

Abstract: The 2004 WHO classification with 4 risk groups is very reliable for predicting both disease-free survival and the time span until tumor-specific death. CK19 staining is a potential additional prognostic marker independent from the WHO criteria for pancreatic endocrine tumors.

Cited by 128 publications

References 19 publications

DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients

DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients

Cleaved caspase-3 immunocytochemical staining for pancreatic islets and pancreatic endocrine tumors: A potential marker for biological malignancy

Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients

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