Prognostic and biological significance of cytokeratin 19 in pancreatic endocrine tumours

Rosa, Stefano La; Rigoli, E; Uccella, Silvia; Novario, Raffaele; Capella, Carlo

doi:10.1111/j.1365-2559.2007.02662.x

Cited by 64 publications

(43 citation statements)

References 24 publications

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“…Although the literature reports discordant opinions on the value of tumour proliferation markers in predicting a patient's prognosis, many studies have shown that Ki-67 expression in histological sections obtained from PETs is an important predictor of their biological behaviour (Pelosi et al 1992, 1996, Rindi et al 1998, Rigaud et al 2001, Butturini et al 2006, La Rosa et al 2007, Vilar et al 2007. The WHO classification of PETs includes Ki-67 expression in the list of parameters (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, Ki-67 is one of the criteria used to grade PETs according to the WHO classification (De Lellis et al 2004). Although recent studies have shown that the expression of cytokeratin 19 (CK 19) predicts long-term survival among patients with PETs (Deshpande et al 2004, La Rosa et al 2007), this marker is not yet widely used in the clinical setting.…”

Section: Introductionmentioning

confidence: 99%

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Cytological Ki-67 in pancreatic endocrine tumours: an opportunity for pre-operative grading

Piani¹,

Franchi²,

Cappelletti³

et al. 2008

Endocrine Related Cancer

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The cytological Ki-67 expression measured on cytological samples collected by endoscopic ultrasonography-guided fine needle aspiration cytology (EUS-FNAC) may provide pre-operative indications for pancreatic endocrine tumours (PETs) management. The aim of our study was to assess reliability of Ki-67 expression measured on cytological samples obtained by EUS-FNAC in patients with PETs. Eighteen patients with PETs underwent EUS-FNAC before surgery. Ki-67 expression was measured on FNACs and on histological sections. Using a cut-off of 2%, percent agreement of Ki-67 expression on cytological and histological samples was 89% (k-statistic: 0.78, 95% confidence intervals (95% CI): 0.5, 1.0). Using cut-off values of 2 and 10%, percent agreement was 78% (k-statistic: 0.65, 95% CI: 0.3, 0.9). Ki-67 expression measured on cytological samples obtained by EUS-FNAC before surgery showed good agreement with that measured on histological samples.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytological Ki-67 in pancreatic endocrine tumours: an opportunity for pre-operative grading

Piani¹,

Franchi²,

Cappelletti³

et al. 2008

Endocrine Related Cancer

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“…Positive staining for CK19 was shown to be a powerful prognostic factor predicting shorter survival, even after controlling for variables such as the number of mitoses, tumor necrosis, and Ki-67 expression (Deshpande et al 2004). CK19 may not be predictive of survival in patients with non-functional PETs (La Rosa et al 2007). Expression of CD10 has also been shown to predict worse survival, and a correlation was found between CD10 expression and the WHO classification where the more malignant tumors were more likely to express CD10 (Deschamps et al 2006).…”

Section: Other Prognostic Factorsmentioning

confidence: 99%

Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors

Halfdanarson¹,

Rubin²,

Farnell³

et al. 2008

Endocrine Related Cancer

343

233

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Pancreatic endocrine tumors (PETs) are uncommon tumors with an annual incidence !1 per 100 000 person-years in the general population. The PETs that produce hormones resulting in symptoms are designated as functional. The majority of PETs are non-functional. Of the functional tumors, insulinomas are the most common, followed by gastrinomas. The clinical course of patients with PETs is variable and depends on the extent of the disease and the treatment rendered. Patients with completely resected tumors generally have a good prognosis, and aggressive surgical therapy in patients with advanced disease may also prolong survival. The epidemiology, prognosis, and established and novel prognostic markers of PETs are reviewed.

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“…A reason for the discrepancy between these studies could be the use of different CK19-directed monoclonal antibodies and/or criteria for evaluation of immunostaining results. We have used the RCK108 clone, which is used by the most other studies and shown to be more reliable for CK19 analysis than the BA17 clone (La Rosa et al 2005).…”

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

confidence: 99%

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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Prognostic and biological significance of cytokeratin 19 in pancreatic endocrine tumours

Abstract: CK19 expression correlates with patient survival only when detected with the RCK108 antibody and mainly in insulinomas. Ki67 index and metastases represent the only two independent predictors of survival.

Cited by 64 publications

References 24 publications

Cytological Ki-67 in pancreatic endocrine tumours: an opportunity for pre-operative grading

Cytological Ki-67 in pancreatic endocrine tumours: an opportunity for pre-operative grading

Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors

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

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