Pancreatic islet cell tumor metastasis in multiple endocrine neoplasia type 1: Correlation with primary tumor size

Lowney, Jennifer K.; Frisella, Margaret M.; Lairmore, Terry C.; Doherty, Gerard M.

doi:10.1067/msy.1998.92561

Cited by 93 publications

(83 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, liver metastasis was only seen in patients with large NFPTs (78 mm and 50 mm). This finding was also true in a report by Lowney et al, where the only patients with large tumors had liver metastasis [26].…”

Section: Discussionsupporting

confidence: 70%

“…Recently, Triponez et al reported that surgery for NFPTs smaller than 2 cm is not beneficial for MEN1 patients, with regard to their life expectancy [25]. On the other hand, a poor correlation between tumor size and malignant behavior has also been documented [26]. Some groups advocate an aggressive surgical approach for MEN1-associated NFPTs [27][28][29][30].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Long-term Follow-up of Patients with Multiple Endocrine Neoplasia Type 1

et al. 2007

View full text Add to dashboard Cite

Abstract. Whether early surgical treatment of non-functioning pancreas islet cell tumor (NFPT) provides a favorable quality of life and life expectancy in patients with multiple endocrine neoplasia type 1 (MEN1) remains controversial. We analyzed the long-term clinical courses and surgical outcomes of 14 Japanese patients with MEN1-associated NFPTs. NFPTs smaller than 20 mm in diameter did not show any apparent growth over a long monitoring period. Furthermore, these small NFPTs did not metastasize to regional lymph nodes or the liver. On the other hand, the development of additional NFPTs or metastasis was found in five of six patients with large (35 mm or larger) NFPTs. Among the seven patients who underwent a partial pancreatectomy, six patients developed impaired glucose tolerance or diabetes. The accumulation of more prospective data is needed to clarify the optimal surgical indications for patients with NFPTs, especially among the Japanese population, which has a relatively low insulin secretion potency compared with nonHispanic white and African-American populations.

show abstract

Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Long-term Follow-up of Patients with Multiple Endocrine Neoplasia Type 1

et al. 2007

View full text Add to dashboard Cite

show abstract

“…We cannot rule out that possibility. However, there is no correlation between the size of primary tumors and metastatic potential in colon and pancreatic cancers (63,64). Furthermore, the American Joint Committee on Cancer staging for colorectal cancer, which is often used to predict prognosis, is not based on the size of the primary tumor.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Ron Kinase Inhibits Mutant Phosphatidylinositol 3-Kinase and Reduces Metastasis in Human Colon Carcinoma

Wang

Rajput

Kan

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Abnormal accumulation and activation of receptor tyrosine kinase Ron (recepteur d'origine nantais) has been demonstrated in a variety of primary human cancers. We show that RNA interference-mediated knockdown of Ron kinase in a highly tumorigenic colon cancer cell line led to reduced proliferation as compared with the control cells. Decreased Ron expression sensitized HCT116 cells to growth factor deprivation stress-induced apoptosis as reflected by increased DNA fragmentation and caspase 3 activation. In addition, cell motility was decreased in Ron knockdown cells as measured by wound healing assays and transwell assays. HCT116 cells are heterozygous for gain of function mutant PIK3CA H1047R. Analysis of signaling proteins that are affected by Ron knockdown revealed that phosphatidylinositol 3-kinase (PI3K) activity of the mutant PI3K as well as AKT phosphorylation was substantially reduced in the Ron knockdown cells compared with the control cells. Moreover, we demonstrated in vivo that knockdown of Ron expression significantly reduced lung metastasis as compared with the control cells in the orthotopic models. In summary, our results demonstrate that Ron plays an essential role in maintaining malignant phenotypes of colon cancer cells through regulating mutant PI3K activity. Therefore, targeting Ron kinase could be a potential strategy for colon cancer treatment, especially in patients bearing gain of function mutant PI3K activity.The receptor tyrosine kinase Ron (recepteur d'origine nantais) belongs to the Met proto-oncogene family (1, 2). Mature Ron is a 180-kDa heterodimer composed of a 40-kDa extracellular ␣-chain and a 150-kDa transmembrane ␤-chain with tyrosine kinase activity (2). Macrophage-stimulating protein is the only ligand that has been identified for Ron (3, 4). Upon ligand binding, Ron dimerizes, becomes autophosphorylated, and transduces a variety of signals that regulate different downstream pathways including Ras/mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), 3 c-Jun N-terminal kinase (JNK), ␤-catenin, and nuclear factor-B (5-12). Ron can be activated through ligand-dependent or -independent mechanisms (3,13,14), which lead to responses important for tumorigenesis and metastasis, including cell scattering, proliferation, motility, and survival (15,16).Ron is normally expressed at relatively low levels in cells of epithelial origin (4). Recent studies have shown that Ron is overexpressed in 47% of breast tumor tissues as compared with benign epithelium and that elevated Ron expression was strongly associated with invasive activity by tumors (17). In addition, Ron is moderately expressed in normal colorectal mucosa, but is significantly increased in the majority of primary human colorectal adenocarcinoma samples (18). Ron overexpression has also been demonstrated in head and neck tumors (19). Furthermore, splice variants of Ron have been identified in human colon cancer. These variants were found to confer constitutive Ron activity, transformation, and tumorige...

show abstract

“…Reports regarding the prognostic significance of pancreatic tumor size vary. No relation between tumor size and metastases, malignancy or overall survival is found in several series reporting on MEN1-related dpNETs (hormonally active and NF; Grama et al 1992, Lowney et al 1998, Lairmore et al 2000, Bartsch et al 2005, Kouvaraki et al 2006, Lopez et al 2011. In the subset of NF-pNETs, larger tumor size was related to a higher rate of metastases and a decreased overall survival (Triponez et al 2006a,b).…”

Section: Prognostic Factorsmentioning

confidence: 99%

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

Pieterman¹,

Conemans²,

Dreijerink³

et al. 2014

Endocrine-Related Cancer

View full text Add to dashboard Cite

Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene lead to loss of function of its protein product menin. In keeping with its tumor suppressor function in endocrine tissues, the majority of the MEN1-related neuroendocrine tumors (NETs) show loss of heterozygosity (LOH) on chromosome 11q13. In sporadic NETs, MEN1 mutations and LOH are also reported, indicating common pathways in tumor development. Prevalence of thymic NETs (thNETs) and pulmonary carcinoids in MEN1 patients is 2-8%. Pulmonary carcinoids may be underreported and research on natural history is limited, but disease-related mortality is low. thNETs have a high mortality rate. Duodenopancreatic NETs (dpNETs) are multiple, almost universally found at pathology, and associated with precursor lesions. Gastrinomas are usually located in the duodenal submucosa while other dpNETs are predominantly pancreatic. dpNETs are an important determinant of MEN1-related survival, with an estimated 10-year survival of 75%. Survival differs between subtypes and apart from tumor size there are no known prognostic factors. Natural history of nonfunctioning pancreatic NETs needs to be redefined because of increased detection of small tumors. MEN1-related gastrinomas seem to behave similar to their sporadic counterparts, while insulinomas seem to be more aggressive. Investigations into the molecular functions of menin have led to new insights into MEN1-related tumorigenesis. Menin is involved in gene transcription, both as an activator and repressor. It is part of chromatin-modifying protein complexes, indicating involvement of epigenetic pathways in MEN1-related NET development. Future basic and translational research aimed at NETs in large unbiased cohorts will clarify the role of menin in NET tumorigenesis and might lead to new therapeutic options.

show abstract

Pancreatic islet cell tumor metastasis in multiple endocrine neoplasia type 1: Correlation with primary tumor size

Cited by 93 publications

References 13 publications

Long-term Follow-up of Patients with Multiple Endocrine Neoplasia Type 1

Long-term Follow-up of Patients with Multiple Endocrine Neoplasia Type 1

Knockdown of Ron Kinase Inhibits Mutant Phosphatidylinositol 3-Kinase and Reduces Metastasis in Human Colon Carcinoma

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

Contact Info

Product

Resources

About