Immunohistochemical analysis of the proliferative activity of neuroendocrine tumors from various organs

Abstract

Small-cell neuroendocrine carcinomas (NECs) of the prostate are believed not to derive from benign orthotopic NE epithelial cells. Instead, an origin from a putative stem cell is actually the most favored concept. Whether this concept can also be applied to neuroendocrine tumors (NETs) of other organs, especially whether there are indications for well-differentiated NET-NEC sequence, is subject of the present study. A double-labeling technique for the proliferation marker MIB-1 and the NE markers chromogranin A (ChrA) and synaptophysin (SNP) was used for the immunohistochemical analysis of 45 well-differentiated NETs, 16 well-differentiated (low-grade) NECs, and 63 high-grade NECs of the esophagus, stomach, small intestine, appendix, colon, lung, prostate, and urinary bladder. The lowest proliferative activity was found in NETs (0.85% of tumor cells), and the highest activity was found in high-grade NECs (72.5%). The expression of ChrA was highest in NETs and lowest in high-grade NECs. None of the NETs and only sporadic cells in low-grade NECs showed double labeling (up to 0.05%). Up to 50% of the tumor cells in high-grade NECs were positive for MIB-1 and SNP. The percentage of double-labeled cells ranged between 0.9 and 39.6 (mean 9.7). No double-labeled cells were found in the normal epithelium adjacent to the tumors. Transitions from NET to NEC could not be observed. NETs and low-grade NECs differ in their proliferative activity from high-grade NECs, suggesting that they may arise from different precursor cell populations.

Downregulation of drs tumor suppressor gene in highly malignant human pulmonary neuroendocrine tumors

“…Therefore, SCLC is suspected to be different from other neuroendocrine tumors. On the other hand, the evidence indicating that low grade neuroendocrine carcinoma (atypical carcinoid) shows intermediate characterictics between SCLC and typical carcinoid was reported (26). Our results presented herein agreed with these studies.…”

Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

“…It is thought to be a useful predictor of aggressive tumor behavior and an indicator of patient survival [43] . Mib-1 is raised against recombinant parts of the Ki-67 antigen [48][49][50][51][52] . Our results showed that the original tumors with higher Mib-1 (Ki-67) labeling index had an increased tendency to grow in the nude mice.…”

Ki-67 labeling index of neuroendocrine tumors of the lung has a high level of correspondence between biopsy samples and surgical specimens when strict counting guidelines are applied

“…Counting 2000 cells (average 4.5 quantified fields) yielded the same result as counting 2 mm2 (average 8.4 quantified fields), which we take as evidence of a plateau effect, indicating that beyond 2000 cells, no further improvement can be obtained. Quantifying Ki-67 LI in HSR, as has become customary [19,28,30,31,40,[71][72][73][74][75][76], is methodologically sound and biologically relevant. Clinical relevance might be found in using Ki-67 LI on biopsies in a grading system of lung NET, as we recently proposed on surgical specimens by introducing the categories of Lu-NET G1, Lu-NET G2, and Lu-NET G3 [33].…”