Neuroendocrine Tumor Grade Research Articles

A single-center retrospective analysis: The correlation of grade, chromogranin-A, SST2 IHC stains, and OctreoScan imaging in small bowel and pancreatic NETs.

e14585 Background: Previous analyses have demonstrated that neuroendocrine tumor (NET) grade correlates well with OctreoScan positivity, SST2, and Chromogranin-A immunohistochemical (IHC) staining. Historically lower grade tumors were more likely to have a higher amplification of STT2 receptors and OctreoScan positivity. There have however been reports of pancreatic neuroendocrine tumors expressing a high degree of SST2 receptors. We hypothesized that tumor origin Chromogranin-A (ChrgA) and SST2 IHC staining would correlate with OctreoScan positivity and Wick's grade, but were unsure if this would be the case with pancreatic NETs. Methods: We retrospectively analyzed 79 formalin-fixed paraffin-embedded tumor specimens based on tumor histological origin for 1) Wick's tumor grade, 2) SST2 receptor, and 3) ChrgA IHC staining. We sought to primarily analyze NETs of the small bowel and pancreas. CT scan evidence of stage IV disease was corroborated with OctreoScan imaging, but only pancreatic primaries were assessed. OctreoScan imaging was graded as positive or negative. Wick's grading system of: 1 = well differentiated; 2 = moderately differentiated; 3 = poorly differentiated; SST2 and ChrgA IHC stains were performed and graded: 1 +, 2+ or 3+. Results: See Table. Conclusions: Although published reports have demonstrated a higher correlation of OctreoScan positivity with lower grade neuroendocrine tumors, our results demonstrate that pancreatic neuroendocrine tumors were consistently higher grade, OctreoScan positive, and ChrgA and SST2 rich. Small bowel tumors were more likely to be lower grade (Wick's grade 1-2) as consistent with published reports. ChrgA and SST2 IHC staining of 2-3+ appeared to correlate with Wick grade in NETs of the small bowel, but were neither sensitive nor specific in those of pancreatic neuroendocrine origin. Primary tumor (NETs) Wick grade 1 Wick grade 2 Wick grade 3 Small bowel 21/56 26/56 9/56 Pancreatic 3/23 8/23 12/23 Chromogranin-A IHC STAIN Small bowel tumors Pancreatic tumors 1+ 2/56 2/23 2+ 5/56 3/23 3+ 49/56 17/23 Neg 0/56 1/23 SST2 IHC STAIN Small bowel tumors Pancreatic tumors 1+ 23/56 3/23 2+ 16/56 10/23 3+ 14/56 8/23 Neg 3/56 2/23 No significant financial relationships to disclose.

The Role of 68Ga-DOTATATE PET in Patients with Neuroendocrine Tumors and Negative or Equivocal Findings on 111In-DTPA-Octreotide Scintigraphy

(111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide scintigraphy is currently the nuclear medicine imaging modality of choice for identifying neuroendocrine tumors. However, there are cohorts of patients in whom scintigraphy findings are negative or equivocal. We evaluated the role of (68)Ga-DOTATATE PET in a selected group of patients with negative or weakly positive findings on (111)In-DTPA-octreotide scintigraphy to determine whether (68)Ga-DOTATATE PET is able to detect additional disease and, if so, whether patient management is altered. Fifty-one patients with a histologically confirmed diagnosis of neuroendocrine tumors were included. Of the 51 patients, 35 who were negative and 16 equivocal for uptake on (111)In-DTPA-octreotide scintigraphy underwent (68)Ga-DOTATATE PET. Findings were compared using a region-by-region analysis. All findings were verified with CT or MRI. After (68)Ga-DOTATATE PET, all cases were reviewed to determine whether the (68)Ga-DOTATATE PET findings resulted in any alteration in management, in terms of suitability for peptide receptor therapy, somatostatin analogs, and surgery. Of the 51 patients, 47 had evidence of disease on cross-sectional imaging or biochemically. (68)Ga-DOTATATE PET was positive in 41 of these 47 patients (87.2%). No false-positive lesions were identified. (68)Ga-DOTATATE PET detected 168 of the 226 lesions (74.3%) that were identified with cross-sectional imaging. (68)Ga-DOTATATE PET identified significantly more lesions than (111)In-DTPA-octreotide scintigraphy (P < 0.001). There was no correlation between (68)Ga-DOTATATE uptake and histologic grade of neuroendocrine tumors. (68)Ga-DOTATATE imaging changed management in 36 patients (70.6%), who were subsequently deemed suitable for peptide receptor-targeted therapy. In patients with negative or equivocal (111)In-DTPA-octreotide findings, (68)Ga-DOTATATE PET identifies additional lesions and may alter management in most cases.

W1136 Grading and Outcome of Rectal Neuroendocrine Tumours

W1136 Grading and Outcome of Rectal Neuroendocrine Tumours

Expression of an activated mammalian target of rapamycin (mTOR) in gastroenteropancreatic neuroendocrine tumors

Gastroenteropancreatic neuroendocrine tumors are rare, and the current WHO classification divides this tumor entity into well-differentiated (neuro)endocrine tumors, well-differentiated (neuro)endocrine carcinomas, and poorly differentiated (neuro)endocrine carcinomas. Poorly differentiated (neuro)endocrine carcinoma is extremely aggressive, and no appropriate therapeutic approach has been established. The mammalian target of rapamycin (mTOR), an important regulator of cell proliferation and protein translation, is activated in various malignancies. Recent phase II trial has revealed the efficacy of mTOR inhibitor (RAD001; everolimus) against low-to-intermediate grade neuroendocrine tumors. However, the beneficial role of mTOR inhibitor against poorly neuroendocrine carcinoma remains uncertain. The purpose of the present study was to determine the activation of mTOR in gastropancreatic neuroendocrine tumors, especially in poorly differentiated neuroendocrine carcinomas. Expression of p-mTOR(Ser2448) was assessed by immunohistochemistry in 20 gastropancreatic neuroendocrine tumors (seven well-differentiated neuroendocrine tumors, four well-differentiated neuroendocrine carcinomas, and nine poorly differentiated neuroendocrine carcinomas). Double immunohistochemistry was performed with p-Akt for patients with high p-mTOR expression. Expression of mTOR was seen in 9 (45%) of 20 gastroenteropancreatic neuroendocrine tumors. High expression of p-mTOR was seen in 6 (67%) of 9 poorly differentiated neuroendocrine carcinomas which was higher than the expression rate of well-differentiated neuroendocrine tumors and carcinomas, 3 (27%) of 11. All large cell neuroendocrine carcinomas showed high p-mTOR expression. Some tumor cells showed positive staining for p-mTOR co-expressed p-Akt. High expression rate of p-mTOR in poorly differentiated neuroendocrine carcinomas (large-cell type) may suggest the potential role of mTOR inhibitors as effective therapeutic agents for this highly malignant disease.

Differential Expression of Glut1 in Pulmonary Neuroendocrine Tumors: Correlation with Histological Grade

BACKGROUNDIncreased glucose uptake, a process that is mediated by glucose transporter (Glut1) proteins, is an important metabolic feature in a variety of cancer cells. The overexpression of Glut1 in human cancers is known to be related to a variety of histopathological parameters, including histological grade, proliferation rate, and lymphatic invasion. The principal objective of this study was to evaluate Glut1 expression in the spectrum of pulmonary neuroendocrine (NE) tumors including typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), and to characterize the relationship between Glut1 expression and the histologic grade of NE tumors.METHODS19 TC, 7 AC, 13 LCNEC, and 6 SCC patients were included in this study. The percentages of Glut1-positive tumor cells in these patients were determined. For statistical analysis, Glut1 expression was subdivided into a Glut1-low expression group (0-30%) and a Glut1-high expression group (31-90%).RESULTSIn our subgroup analyses, the histological grade of pulmonary neuroendocrine (NE) tumors was significantly correlated with Glut1 expression; TC (n=19, 3.6+/-4.2%), AC (n=7, 20.0+/-4.9%), LCNEC (n=13, 60.0+/-21.1%), and SCC (n=6, 74.2+/-16.9%). Glut1-high expression was significantly associated with high-grade NE tumors such as LCNEC and SCC (n=19, 62.6+/-21.0%) (p=0.000).CONCLUSIONSThe results of this study appear to indicate that Glut1 overexpression is a consistent feature of high-grade NE lung tumors.

TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system

Criteria for the staging and grading of neuroendocrine tumors (NETs) of midgut and hindgut origin were established at the second Consensus Conference in Frascati (Rome) organized by the European Neuroendocrine Tumor Society (ENETS). The proposed tumor-node-metastasis (TNM) classifications are based on the recently published ENETS Guidelines for the Diagnosis and Treatment of gastroenteropancreatic NETs and follow our previous proposal for foregut tumors. The new TNM classifications for NETs of the ileum, appendix, colon, and rectum, and the grading system were designed, discussed, and consensually approved by all conference participants. These proposals need to be validated and are meant to help clinicians in the stratification, treatment and follow-up of patients.

TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system

The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor–node–metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.

Diagnosis and treatment of lung cancer – Non-small cell lung cancer, small cell lung cancer and carcinoids

BACKGROUND: The prognosis of lung tumors is determined by histology and staging (nodal status). The most common tumor is non-small cell lung carcinoma (NSCLC) with a 5-year survival rate of 67 % (stage IA) to 1 cm), especially in PET-positive cases. Adjuvant chemotherapy is used in clinical trials. Small-cell lung cancer (SCLC, neuroendocrine tumor grade III) has a poor prognosis, and is treated with chemotherapy; resection may be performed in early stages. Neuroendocrine tumors grade I (typical carcinoid) are resected by segmentectomy, lobectomy, or bronchoplastic resection. Neuroendocrine tumors grade II (atypical carcinoids) are treated like NSCLC. CONCLUSIONS: The incidence of lung cancer is decreased by tobacco control, and the chances of survival are improved by early detection and multimodality regimens.

Immunohistochemical Staining of Cytologic Smears With MIB-1 Helps Distinguish Low-Grade From High-Grade Neuroendocrine Neoplasms

Neuroendocrine neoplasms (NENs) of the lung and gastrointestinal tract constitute a pathologic and biologic spectrum of tumors. Accurate cytologic diagnosis of a neuroendocrine neoplasm is important since definitive treatment frequently is based on low-and high-grade categories without histologic sampling. In many instances, however, low- and high-grade NENs share cytologic features, hindering a precise classification. Since the histologic diagnostic criteria for separation of low- from high-grade categories can be based on the proliferation rate, we proposed to evaluate the usefulness of the immunocytochemical stain for the proliferation marker MIB-1 in the grading of NENs. Cytologic preparations of 63 NENs were retrieved from the files of Memorial Sloan-Kettering Cancer Center, New York, NY. One representative alcohol-fixed slide from each case was destained and restained immunocytochemically for MIB-1. When MIB-1 immunoreactivity was considered, all low-grade NENs showed immunoreactivity in fewer than 25% of the neoplastic cells, and all high-grade NENs demonstrated immunoreactivity in more than 50% of neoplastic cells. Our study demonstrates that MIB-1 dramatically stratifies NENs as low-grade or high-grade. Therefore, the proliferation index also correlates with grade of NEN in cytology specimens.

Molecular biology of neuroendocrine lung tumors

Molecular biology of neuroendocrine lung tumors