Neuroendocrine Differentiation in Colorectal Carcinomas Assessing its Prognostic Significance

Atasoy, Pınar; Ensarı, Arzu; Demirci, Salim; Kurşun, Nazmiye

doi:10.1177/030089160308900111

Cited by 21 publications

(22 citation statements)

References 10 publications

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“…Accordingly, Syversen and collegues [14] also demonstrated a poorer survival prognosis in patients with positive expression of neuroendocrine markers (CgA, NSE). These results are in accordance to the published data of Atasoy and collegues [15] who also reported a poorer prognosis in CgA-positive colorectal cancer. Moreover, the results of Hamada and collegues [16] indicated that neuroendocrine dif- ferentiation is an independent prognostic factor in patients with primary colorectal cancer, defining a poor survival time in positive immunoreactivity for CgA.…”

Section: Discussionsupporting

confidence: 93%

“…There was no carcinoma which expressed all three markers, and only 3% (3/94) showed a combination of at least two markers. On the first view, these figures on positive expression seem to be below the published data with mean positive expression rates of neuroendocrine differentiation between 30 and 40% [13][14][15][16][17]. However, analyzing our detection rates in detail, the detection rates seem to be in the range, as we excluded undifferentiated or mucinous adenocarcinomas from our analysis.…”

Section: Discussioncontrasting

confidence: 57%

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Neuroendocrine Differentiation in Primary Rectal Cancer: Immune Histology with Prognostic Impact?

Schwandner¹,

Hilbert²,

Broll³

et al. 2007

Visc Med

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Background: The aim of this study was to determine the incidence and prognostic significance of neuroendocrine differentiation in primary rectal cancer with special reference to ki-67 staining index. Methods: Formalin-fixed and paraffin-embedded tissue sections of 94 rectal carcinomas were used for immunohistochemical analysis of chromogranin A (CgA), synatophysin (Syn) and neuron-specific enolase (NSE). Inclusion criteria were sporadic rectal adenocarcinoma resected curatively by total mesorectal excision, adjuvant radiochemotherapy in UICC stages II and III, and complete intrainstitutional follow-up. Results of immunohistochemistry were correlated with clinical and histopathologic data. End points of analysis were tumor progression and 5-year survival. Statistics included univariate and multivariate analysis. Results: Of 94 rectal carcinomas studied, 20% (19/94) were CgA-positive, 7% (7/94) were Syn-positive, and 3% (3/94) were NSE-positive. No expression of neuroendocrine markers was documented in 72% (68/94). There was no carcinoma which expressed all three markers, and only 3% (3/94) showed a combination of at least two markers. Neither for Syn nor for NSE any significant association with clinical or histopathological variables could be found. Expression of CgA significantly correlated with age and differentiation (p = 0.03). Within a mean follow-up of 50 months, tumor progression occurred in 14 patients (15.4%): 2 patients had local recurrences (isolated), 4 had local and distant recurrence and 8 had metachronous distant metastases without local recurrence. Only UICC stage and preoperative CEA serum level were significantly associated with tumor progression, whereas the neuroendocrine markers failed to show any correlation. Focusing solely on distant recurrence, the incidence of metachronous distant metastases was significantly associated with UICC stage, depth of invasion, preoperative CEA serum level, and CgA expression (23.5% in CgA-positive vs. 5.9% in CgA-negative tumors, p = 0.02). The neuroendocrine markers did not show any relation with survival prognosis. Correlated to ki-67 expression, 89.5% (17/19) of CgA-positive tumors showed a concurrent high ki-67 expression of more than 40% of cells (staining index > 0.4). Conclusions: The expression of the neuroendocrine marker CgA seems to have a prognostic impact in primary rectal cancer for the incidence of metachronous distant recurrence. It seems that the increased proliferation (assessed by ki-67 staining index) could play a role in curatively resected rectal cancer.

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 57%

Neuroendocrine Differentiation in Primary Rectal Cancer: Immune Histology with Prognostic Impact?

Schwandner¹,

Hilbert²,

Broll³

et al. 2007

Visc Med

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“…A study by Atasoy et al [13] including 50 patients with neuroendocrine differentiated tumors revealed that chromogranin A positivity was closely correlated with prognosis. We did not find such a correlation in our patients (P = 0.65); in addition, prognosis did not correlate with the specific determinants of neuroendocrine tumors, synaptophysin and NSE.…”

Section: Discussionmentioning

confidence: 98%

Gastroenteropancreatic neuroendocrine tumors: 10-year experience in a single center

et al. 2009

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Neuroendocrine tumors originate from neuroendocrine cells and occur in a wide spectrum from carcinoid tumors to small cell carcinomas. Although the World Health Organization determined clinical and histological features to predict prognosis for such tumors, they may not be valid on an individual basis. This study investigates the clinical, pathologic and prognostic characteristics of gastroenteropancreatic neuroendocrine tumors that presented to the Medical Oncology Outpatient Clinic, İstanbul University, Cerrahpaşa School of Medicine from 1995 to 2006 (n=86). The mean age of the patients was 52±14 and the male-to-female ratio was 0.87. The most common site of involvement was the stomach. Midgut intestinal tumors seemed to have significant female predominance compared to hindgut intestinal tumors (P=0.016). Most of the patients had metastatic disease with a prevalence of 34.9%. Poorly differentiated tumors and mixed neuroendocrine carcinomas were significantly larger than 2 cm (P=0.0001). The median survival was 139 months and the highest mortality was for colorectal tumors (36%). While univariate analysis revealed that the number of lymph nodes (P=0.008), multiple foci (P=0.034), metastases (P=0.022) and stage (P=0.034) correlated significantly with survival, there was no independent variable in the multivariate analysis. Hindgut tumors had significantly more Ki-67, mitosis and necrosis compared to others (P≤0.05). In this retrospective study, the clinical, pathologic and prognostic characteristics of gastroenteropancreatic tumors from a single center from Turkey were analyzed and compared with the current medical literature.

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“…Focal NE differentiation is not mentioned in the WHO classification of tumours of the digestive system [25], although there are reports in the literature on the occurrence of NE differentiation in esophageal [26], gastric [42], colorectal [2,4,19,22,23,30,43] and extrahepatic duct carcinomas [28]. The amount of NE cells is variable in these tumours and is related to the method used to identify such NE differentiation [43].…”

Section: Non-ne Carcinomas With Focal Ne Component (<30%)mentioning

confidence: 99%

The grey zone between pure (neuro)endocrine and non-(neuro)endocrine tumours: a comment on concepts and classification of mixed exocrine–endocrine neoplasms

2006

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Terms such as "mixed endocrine-exocrine carcinoma" (MEEC) and "adenocarcinoma with neuroendocrine (NE) differentiation" (ADC-NE) identify tumours belonging to the spectrum of neoplasms with divergent exocrine and (neuro)endocrine differentiation. These tumours display variable quantitative extent of the two components, potentially ranging from 1 to 99%, and variable structural patterns, ranging from single scattered NE cells to a well-defined NE tumour cell population organized in organoid, trabecular or solid growth patterns. In the present report, the grey zone of tumours/carcinomas with mixed NE and non-NE features is explored for various organs. From a practical point of view, MEECs differ from carcinomas with focal NE differentiation by (1) the extension of each component (more than 30%) and (2) the structural pattern of the NE component, either organoid for well-differentiated or solid/diffuse for poorly differentiated cases. In MEECs, the most aggressive cell population drives the clinical behaviour. Conversely, ADC-NE generally do not show a different clinical outcome, compared to the corresponding conventional forms, except for prostatic adenocarcinoma, in which NE cells are a negative prognostic factor. The recognition of MEECs may be of relevance for a targeted therapeutic strategy, foreseeing the use of biotherapies similar to those proposed for pure NE tumours.

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Neuroendocrine Differentiation in Colorectal Carcinomas Assessing its Prognostic Significance

Abstract: Our results show that chromogranin A is the most sensitive and specific neuroendocrine marker. Chromogranin A positivity appears to bear a poor prognosis in patients with colorectal cancers.

Cited by 21 publications

References 10 publications

Neuroendocrine Differentiation in Primary Rectal Cancer: Immune Histology with Prognostic Impact?

Neuroendocrine Differentiation in Primary Rectal Cancer: Immune Histology with Prognostic Impact?

Gastroenteropancreatic neuroendocrine tumors: 10-year experience in a single center

The grey zone between pure (neuro)endocrine and non-(neuro)endocrine tumours: a comment on concepts and classification of mixed exocrine–endocrine neoplasms

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