Chromosomal alterations detected by comparative genomic hybridization in nonfunctioning endocrine pancreatic tumors

Floridia, Giovanna; Grilli, Giulia; Salvatore, Marco; Pescucci, Chiara; Moore, Patrick S.; Scarpa, Aldo; Taruscio, Domenica

doi:10.1016/j.cancergencyto.2004.04.015

Cited by 27 publications

(22 citation statements)

References 21 publications

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“…Abnormality of type 1 multiple endocrine neoplasia (MEN1) gene is restricted to foregut tumors, while 18q chromosomal abnormality is more frequently observed in lower gut tumors. Unexpectedly, high frequency of genetic defects is reported, suggesting accumulation of genetic defects as the background required for malignant progression [27][28][29][30].…”

Section: Tumor Classification and Prognostic Factorsmentioning

confidence: 99%

Prognostic Factors in Gastrointestinal Endocrine Tumors

et al. 2007

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The gastrointestinal endocrine tumors are neoplastic lesions with often elusive malignant clinical behavior. The current WHO classification attempted to define a more effective approach by introducing the concepts of cell differentiation and site-specific malignancy, as well as specific criteria for carcinoma definition. WHO clinicopathological correlations embed the prognostic features: degree of cell differentiation, angioinvasion, proliferation fraction as assessed by mitotic index and Ki67, size, and functional activity. Other prognostic variables have been recognized, most of which related to specific biological features of neuroendocrine cancer cells. Nonetheless, the presence of liver or distant metastases are the prognostic variables ultimately determining the patients' fate in terms of survival and/or therapy response. A recent proposal of tumor grading and tumor, nodes, and metastases (TNM) staging aims at a simple and practical system for patients stratification. Application of such proposal should be implemented in routine clinical practice.

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Section: Tumor Classification and Prognostic Factorsmentioning

confidence: 99%

Prognostic Factors in Gastrointestinal Endocrine Tumors

et al. 2007

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“…In these, the most frequent imbalance (loss) was scored for chromosome 11. Loss of chromosome 11 has been previously reported (13,23). In our study, 11p11 was found lost in 73% of the nonfunctioning tumors with imbalances, followed by 11p14–15 and 11q23 (64% of the tumors), and 11p12–13 and 11q22 in 55%.…”

Section: Discussionmentioning

confidence: 84%

“…Information on genomic imbalances in nonfunctioning (i.e. without hormone production) PNEN detected by CGH is limited to 54 cases (13–16). Common genomic imbalances involved gains of 7q, 17q, and 20q and losses of 6q, 11p, and 11q.…”

Section: Introductionmentioning

confidence: 99%

Loss of 11p11 is a frequent and early event in sporadic nonfunctioning pancreatic neuroendocrine neoplasms

et al. 2014

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The pathogenesis of sporadic pancreatic neuroendocrine neoplasms (PNENs) is poorly understood. To gain insight into the genetic mechanisms underlying this tumor entity, we performed genome-wide screening of 16 surgical specimens from 15 patients with sporadic PNEN, combining G-band karyotyping and high resolution comparative genomic hybridization (HR-CGH). G-banding revealed abnormal karyotypes in 2 of 10 tumor samples analyzed. DNA copy number changes were detected in 13 samples, whereas three tumors showed a balanced genome. Gains were more frequent than losses in the nonfunctioning tumors (n=13). Common gains were scored at 5p12–13, 4q13–24, 5p15, 5q11–31, and 9q21–22. Common losses were scored at 11p11, 11p14–15, 11q23, 11p12–13, and 11q22. The average number of copy aberrations (ANCA index) was 12 for 13 nonfunctioning primary tumors, 4.8 for the nonfunctioning tumors with low Ki-67 (≥5%), 21.2 for the tumors with high Ki-67 (<5%), 2.5 for small tumors (<3.5 cm), and 17.8 for large tumors (≥3.5 cm). There was a statistically significant difference in the ANCA index between the groups defined by Ki-67 and tumor size. Nonfunctioning tumors with low Ki-67, no distant metastasis and small size had few aberrations detected by HR-CGH, but frequent loss of material from chromosomal band 11p11. The present study indicates the existence of distinct cytogenetic patterns in sporadic nonfunctioning PNEN. Loss of chromosomal band 11p11 might indicate a primary pathogenetic event in these tumors.

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“…Furthermore, sequence data from the genome of sporadic pancreatic NENs have indicated that mutations almost exclusively occur in tumor suppressor genes (e.g., MEN-1, PTEN), while genes responsible for secretion, and therefore function, are not mutated [31]. The proposal for a molecular signature unique to nonfunctioning tumors [32,33] has little molecular support.…”

Section: Genetics and Hereditary Tumor Syndromesmentioning

confidence: 99%

The archaic distinction between functioning and nonfunctioning neuroendocrine neoplasms is no longer clinically relevant

Modlin

Moss

Gustafsson

et al. 2011

Langenbecks Arch Surg

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Nonfunctional tumors are usually diagnosed incidentally and at a later stage largely because either they do not secrete a bioactive product or do so, but in a form that is either inactive or in quantities that have no discernible effect. Nevertheless, the histopathology is indistinguishable from functional NENs, and tumors exhibit somatostatin receptor expression, and positive immunohistochemistry for neuroendocrine cell markers (CgA, NSE/synaptophysin). Similarly, their rates of growth and metastatic behavior are, like other NENs, predictably based on staging and grading (mitotic rate and Ki67 expression). Both types are diagnosed biochemically (CgA) and by imaging in an identical fashion with computed tomography, magnetic resonance imaging, somatostatin receptor scintigraphy, and endoscopic ultrasound. NENs, irrespective of function or bioactive secretory profile, respond with equal efficacy to the same regimen of surgery or antitumor drugs (e.g., somatostatin analogs with or without tyrosine kinase inhibitors/antiangiogenics or cytotoxics) depending on grade. Given the efficacy of somatostatin analogs in increasing progression free survival, nonfunctional NENs should be managed identically to symptomatic NENs. The consideration of NENs as functional or nonfunctional is an archaic clinical concept that should be discarded since the tumors are indistinguishable at a cellular, biological, and morphological level. All current evidences indicate that their diagnosis and treatment should follow the same common principles.

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Chromosomal alterations detected by comparative genomic hybridization in nonfunctioning endocrine pancreatic tumors

Cited by 27 publications

References 21 publications

Prognostic Factors in Gastrointestinal Endocrine Tumors

Prognostic Factors in Gastrointestinal Endocrine Tumors

Loss of 11p11 is a frequent and early event in sporadic nonfunctioning pancreatic neuroendocrine neoplasms

The archaic distinction between functioning and nonfunctioning neuroendocrine neoplasms is no longer clinically relevant

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