Significance Of Neuroendocrine Differentiation Research Articles

Prognostic Threshold of Neuroendocrine Differentiation in Gastric Carcinoma: a Clinicopathological Study of 945 Cases.

PurposeThe significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications.Materials and MethodsImmunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters.ResultsIn total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED.ConclusionsGC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.

Abstract P6-08-02: Primary neuroendocrine carcinoma of the breast – lessons learned from a ten year analysis of the National cancer data base (NCDB)

Abstract Primary neuroendocrine carcinomas of the breast (NECB) is rare (a reported incidence &amp;lt;5%). The significance of neuroendocrine differentiation and its impact on diagnosis, treatment and prognosis of NECB is controversial and based primarily on results from small retrospective case series reports. Our study objective is to define incidence, clinicopathologic characteristics, treatment patterns and prognosis of NECB and compare these to the most common invasive breast carcinoma (BC)-ductal (IDC). A retrospective observational comparison study of NCDB patients (pts) from 2004 to 2014 compared all NECB pts with ICD-O-3 diagnosis codes 8246/3, 8041/3 and 8574/3 (well-differentiated neuroendocrine tumor, poorly differentiated/small cell carcinoma and invasive BC with neuroendocrine differentiation, respectively) to the same number of randomly selected IDC (8500/3) pts. Patients' clinicopathologic characteristics, treatment, and overall survival (OS) were analyzed using frequency statistics, chi-square, Kaplan-Meier and logistic regression. 1,790,023 pts had BC; 1,316,696=IDC (73.6%); 957=NECB (.0005%). NECB pts were significantly (p&amp;lt;.05) more likely to be: older, have larger tumors, grade 3 tumors, positive lymph nodes, ER, PR, HER2-negative tumors and higher TNM stage when compared to IDC. NECB pts were less likely to undergo surgery, radiation and anti-estrogen therapy. NECB pts had significantly worse 10-year OS than IDC pts (p&amp;lt;.001), with NECB pts being 3.4 times more likely to die in 10-years (95%CI 2.7-4.3). Our study is the largest study to date on NECB (incidence 0.0005%) showing that NECB is aggressive and carries a significantly worse prognosis than IDC. Prospective randomized clinical trial(s) are unlikely, yet needed in order to conquer the current challenges of patients with NECB. DemographicsNECBIDC (random sample)Adjusted Odds Ratio *=p&amp;lt;.0595%CI95%CI N=957N=957 LowerUpper N % Age ≤4047 4.970 7.3R 41-69564 58.9616 64.4NS ≥70346 36.2271 28.31.9*1.32.8Race White809 84.5804 84R Black118 12.3105 11NS Other21 2.239 4.1NS Unknown9 .99 .9 Tumor size mm ≤543 4.588 9.4R (tumor ≤10mm) 6-1096 10.1172 18.3R (tumor ≤10mm) 11-20196 20.6339 36.1NS 21-50382 40.2264 28.13.1*2.44.1≥51160 16.851 5.46.7*4.69.9Unknown68 7.222 2.3 Grade 193 9.7181 18.9R 2208 21.7372 38.9NS 3480 50.2360 37.62.6*1.93.5Unkown176 18.444 4.6 # of node(s) positive 0372 38.9577 60.3R 1 to 3194 20.3193 20.21.5*1.21.94 to 947 4.955 5.7NS ≥10328 34.3121 12.64.2*3.35.4Unknown16 1.711 1.1 TNM stage I245 25.6502 52.5R II334 34.9293 30.62.3*1.92.9III121 12.692 9.62.7*1.93.7IV166 17.335 3.79.7*6.514.4Unknown89 9.326 2.7 ER (+)540 62.6730 78.2R (-)322 37.4203 21.8.5*.4.6PR (+)474 55.8636 68.2R (-)375 44.2296 31.8.6*.5.7HER2 (+)15 3.474 15.4R (-)428 96.6402 84.5.2*.1.3Surgery Yes724 79.4900 95.8R No188 20.639 4.2.17*.1.2Chemotherapy No335 35409 42.7R Yes622 65548 57.31.4*1.21.7Anti-estrogen tx No460 54.6292 34.2R Yes382 45.4562 65.8.4*.4.5Radiation No444 46.4398 41.6R Yes513 53.6559 58.4.8*.6.910-year overall survival Odds ratio Dead350 40.5141 16.63.4*2.74.3Alive515 59.5710 83.4 R = Referent NS = Not significant Citation Format: Rose CE, Heidel RE, Bell JL, Orucevic A. Primary neuroendocrine carcinoma of the breast – lessons learned from a ten year analysis of the National cancer data base (NCDB) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-02.

Prognostic significance of neuroendocrine differentiation in colorectal adenocarcinoma

Objective To investigate the significance of neuroendocrine differentiation in the colorectal adenocarcinoma.Methods Eighty-two cases of colorectal adenocarcinoma operated in the Sun Yatsen Memorial Hospital of Sun Yat-sen University in 2008 were analyzed retrospectively.Immunohistochemistry was used to detect the specific neuroendocrine markers,including chromogranin A (CgA) and synaptophysin (Syn).Results Fifteen out of 82 cases (18.3％) were positive for at least one marker.In 15 cases of colorectal adenocarcinoma,there were 6 cases of neuroendocrine differentiation for stage Ⅱ,6 cases for stage Ⅲ,and 3 cases for stage Ⅳ ; 6 cases of high differentiation,6 cases of moderate differentiation,and 3 cases of poor differentiation ; the rectum was involved in 4 cases,sigmoid colon in 4 cases,descending colon in 1 case,transverse colon in 1 case,and ascending colon in 5 cases.The recurrence and/or metastasis rate in the neuroendocrine differentiation group was significantly higher than in non-neuroendocrine differentiation group (66.7％ vs.29.8％,P ＜ 0.01).The five-year survival rate in neuroendocrine differentiation group was significantly lower than in non-neuroendocrine differentiation group (26.7％vs.52.2％,P ＜ 0.05).Conclusion The expression of specific neuroendocrine markers in the colorectal adenocarcinoma would lead to a poor prognosis of this disease.To promote routine detection of these two specific neuroendocrine makers by immunohistochemistry in the colorectal adenocaicinoma would enhance the judgment of prognosis. Key words: Colorectal adenocarcinoma; Neuroendocrine ; Differentiation ; Prognosis

Significance of Neuroendocrine Cell Differentiation in Specimens from Patients with Prostate Cancer

Purpose: The neuroendocrine cell (NEC) is one of the constitutional cells found in the prostate gland; these cells secret neurotransmitters. These neuroendocrine products have been associated with prostate cancer progression. We evaluated the significance of neuroendocrine differentiation (NED) in radical prostatectomy specimens. Materials and Methods: We studied 45 patients who underwent bilateral pelvic lymphadenectomy and radical prostatectomy. The patients were classified into three groups according to their pathological stage. Group A included cases with organ confined tumors, Group B local advanced tumors and Group C cases had any T stage and lymph node metastasis. The cellular expression of chromogranin A in matched samples from the same patients was evaluated by immunohistochemical staining using commercially available monoclonal antibodies. Results: Sixteen (35.6%) tumors had chromogranin A stained cells. Chromogranin A immunoreactivity was greatest in cases with lymph node involvement (75.0%) compared to those with primary prostate cancer (5.9% in group A and 37.5% in group B). Pathologically advanced tumors or tumors with the highest histological grades were associated with increased NED. The median staining score was 0 in Group A, 0 in Group B and 1 in Group C. The logistic regression analysis the odds ratio for group C cases showed a relative risk of 32.07 (95% CI: 2.783-369.416) for NED compared to Group A. An increased prostate-specific antigen (PSA) and Gleason score were also associated with the NED. Conclusions: The degree of NEC immunohistochemical staining using the chromogranin A monoclonal antibody was marginally useful for predicting the outcome in prostate cancer patients after radical prostatectomy, especially in node positive patients. However, it is important to determine a therapeutic plan for patients with low PSA and internal organ metastasis. (Korean J Urol 2008;49:585-591) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

The significance of neuroendocrine differentiation in adenocarcinoma of the esophagus and esophagogastric junction after preoperative chemoradiation

Esophageal and esophagogastric junction (EGJ) adenocarcinomas frequently have neuroendocrine (NE) differentiation, but the significance of NE differentiation in patients who have undergone preoperative chemoradiation and resection remains unclear. The authors evaluated the presence of NE differentiation in esophageal and EGJ adenocarcinomas by immunohistochemistry for chromogranin A and synaptophysin and evaluated the clinical significance of NE differentiation in 83 patients (10 patients who had a complete tumor response and 73 patients who had residual tumor in resection specimens) who received preoperative chemoradiation. Of 73 patients who had residual tumor after preoperative treatment, 52% showed NE differentiation. The proportion of tumor cells with NE differentiation had increased from 6% +/- 18% in pretreatment biopsy specimens to 47% +/- 42% (P = .00003) in posttreatment resection specimens in 30 patients who had paired pretreatment biopsy and resection specimens available. Disease-free survival (P = .002) and overall survival (P = .006) were significantly better in patients who had a complete tumor response than in patients who had residual tumor. Among patients who had residual tumor after preoperative chemoradiation, disease-free survival (P = .03) and overall survival (P = .045) were significantly better in patients who had residual tumor without NE differentiation than in patients who had residual tumor with NE differentiation. In multivariate analysis, the presence of NE differentiation in residual tumor was a prognostic factor for worse disease-free survival (P = .02) independent of pathologic stage and extent of residual tumor. The results from this study suggested that tumor cells with NE differentiation were more resistant to neoadjuvant chemoradiation in patients with esophageal and EGJ adenocarcinomas. The presence of NE differentiation in residual tumor was associated with poor survival after preoperative neoadjuvant therapy.

The possible role of chromogranin A as a prognostic factor in organ-confined prostate cancer

The clinical significance of neuroendocrine differentiation in patients who have undergone surgery for localized prostate cancer is still unclear. The aims of this study were to assess the relationship between serum neuroendocrine markers and well-known prognostic factors in prostate cancer (pathological staging, definitive Gleason score and serum PSA) and to search for correlations between serum chromogranin A (CgA) levels and pathological findings. Forty-one consecutive patients who had undergone radical retropubic prostatectomy for clinically localized prostate cancer were evaluated. Serum PSA, CgA and neuron-specific enolase were measured immediately before surgery. Twenty-six surgical specimens were phenotypically and immunohistochemically evaluated using an antibody against CgA. Significant correlations were found between serum CgA, pathological staging and Gleason score (p=0.049 and p=0.038, respectively). Serum CgA did not correlate with PSA, patient age, or immunohistochemical findings. There was a significant correlation between positive immunohistochemical CgA staining and Gleason score (p=0.014). An increase in serum CgA levels, independent of PSA values, might be the expression of pathologically more advanced tumor stage and higher Gleason score; this could help to identify a high-risk patient group eligible for adjuvant therapy.

Prognostic Significance of Neuroendocrine Differentiation in Non-small Cell Lung Cancer Patients' Survival

Objective: To observe the relationship between non-small cell lung cancer with neuroendrocrine differentiation (NSCLC-NE) and patients' postoperative survival. Methods: During April 1997 to April 1999, 98 cases of lung cancer were surgically treated. The tumor specimens of the patients were stained by NE markers, i.e. neuron specific enolase (NSE) and synaptophysin (SY). The intensity of NE markers reaction was divided as "+", "++", "+++" scale groups. The same specimens were also examined under an electron microscope for the specific neuroendocrine granules. All enrolled patients were followed up for 36 months, and the longest follow-up time was 60 months. The COX proportional hazard model multivariate analysis was applied to observe the relationship between the NSCLE-NE and the patients' postoperative survival. Results: In 91 cases of NSCLC, 63.7% (58/91) were positive for NE stain reaction. Among them, 59.3% (54/91) were positive for NSE and 24.1% (22/91) for SY. 48.4% (44/91) were considered as NSCLC-NE by the combination of NE marker stain reaction and electron microscopic examination. COX proportional hazard model multivariate analysis showed that the NSCLC-NE patients' survival was significantly shortened (P=0.048). The following factors were related to NSCLC-NE patients' survival: lung cancer cell differentiation (P=0.006), clinical lung cancer stage (P=0.001), the NE markers reaction (P=0.054). Conclusion: NSCLE-NE is significantly related to the cancer cell differentiation and the patients' postoperative survival. The NE markers should be applied clinically as one of prognostic factors to evaluate the postoperative survival of NSCLC patients.

A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells.

A transgenic mouse model of metastatic prostate cancer has been developed that is 100% penetrant in multiple pedigrees. Nucleotides -6500 to +34 of the mouse cryptdin-2 gene were used to direct expression of simian virus 40 T antigen to a subset of neuroendocrine cells in all lobes of the FVB/N mouse prostate. Transgene expression is initiated between 7 and 8 weeks of age and leads to development of prostatic intraepithelial neoplasia within a week. Prostatic intraepithelial neoplasia progresses rapidly to local invasion. Metastases to lymph nodes, liver, lung, and bone are common by 6 months. Tumorigenesis is not dependent on androgens. This model indicates that the neuroendocrine cell lineage of the prostate is exquisitely sensitive to transformation and provides insights about the significance of neuroendocrine differentiation in human prostate cancer.

Neuroendocrine differentiation and nerves in human adrenal cortex and cortical lesions.

Neuroendocrine differentiation and nerve distribution were studied in sections from human cortex (n=11) and cortical lesions (hyperplasias, n=9; adenomas, n=13; carcinomas, n=14) with four markers, namely chromogranin A(CgA), synaptophysin (SYN), neuron-specific enolase (NSE), protein gene product (PGP) 9.5 and small synaptic vesicle protein (SV)2. All but two cases expressed neuroendocrine differentiation. NSE was the most commonly occurring marker and the NSE immunoreactive cells were detected in normal cortex, mainly in zona glomerulosa, as well as in adenomas and carcinomas. SYN and PGP 9.5 immunoreactive cells were especially prominent in the carcinomas, while SV2 immunoreactive cells were seen mainly in normal cortex. The difference in distribution pattern of the neuroendocrine markers between adenomas and carcinomas was not so distinct that it can be used for histopathological diagnosis. The significance of neuroendocrine differentiation in cortex and cortical lesions is uncertain, but may reflect an involvement in special hormonal functions. No obvious relationship was found between the clinical syndromes and the degree of neuroendocrine differentiation. Three of the neuroendocrine markers also visualized nerve structures. PGP 9.5, which is regarded as the most 'general' nerve marker, visualized more nerve structures than did the other markers. Normal cortex contained most immunoreactive nerves, whereas they were less numerous in hyperplasias and sparse or even absent in the neoplasms. The nerves appeared among the parenchymal cells but were particularly prominent around vessels. The results suggest that the cortical nerves influence not only the regulation of the blood supply but also the hormonal regulation at the cellular level.

Prognostic significance of neuroendocrine differentiation in clinically localized prostatic carcinoma

Prognostic significance of neuroendocrine differentiation in clinically localized prostatic carcinoma

Advances in the biology of lung cancer. Clinical significance of neuroendocrine differentiation

Advances in the biology of lung cancer. Clinical significance of neuroendocrine differentiation