Increased neuroendocrine cells in resected metastases compared to primary colorectal adenocarcinomas

Abstract

Neuroendocrine differentiation has been described in rectal adenocarcinomas receiving neoadjuvant therapy prior to radical surgery, but its clinical relevance is controversial and no data are currently available in colorectal carcinoma metastases as compared to primary tumors. The presence of chromogranin A positive tumor cells was investigated by means of immunohistochemistry on surgical specimens from 54 primary colorectal carcinomas and their corresponding metastases, resected at diagnosis or during tumor progression. In 47 patients, tumor metastases were resected 1 month to 12 years after chemotherapy and/or radiotherapy, while in the remaining seven patients no additional therapy after primary surgery was performed. In primary tumors, neuroendocrine differentiation was found in 12/54 cases (22.2%) as compared to 25/54 metastatic lesions (46.3%; p=0.01). The presence of neuroendocrine phenotype was not correlated with any clinical pathological parameter nor with a different proliferation index. However, patients having neuroendocrine cells in the primary tumor had a significantly shorter survival from the time of metastatic spread than those having not (33.3 vs. 55.5 months; p=0.04). In summary, our data show that colorectal carcinoma metastases contain a higher percentage of neuroendocrine differentiated cells as compared to their corresponding primaries, a finding possibly related to the influence of chemotherapy in neuroendocrine differentiation during colorectal carcinoma progression.

Is neuroendocrine differentiation useful to discriminate primary sinonasal intestinal-type adenocarcinomas from metastatic colorectal adenocarcinomas?

“…Neuroendocrine differentiation, defined by immunohistochemical staining with antichromogranin A and antisynaptophysin antibodies, has been described in several types of adenocarcinomas 3. Some authors suggested that neuroendocrine differentiation was useful for distinguishing ITAC from sinonasal metastatic CRA 4 5.…”

Digestive System Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms

“…Nevertheless, metachronous metastases are rarely biopsied, and nuclear medicine tools cannot help distinguishing between adenocarcinoma and PDNEC because, for example, both components display 18 FDG positron-emitting tomography positivity, and negative somatostatin receptor scintigraphy due to lack of somatostatin receptors expression [83] . The cell type present in tumour emboli on resected primary tumours may be similar to that found in lymph node and distant metastases; thus, its analysis could be an alternative to metastasis biopsy [22] .…”

“…Besides, radiotherapy and chemotherapy might favour genomic instability and transdifferentiation towards the PDNEC component, based on observations that the number of neuroendocrine markers-positive cells increased following neo-adjuvant treatments [18,65] . This strongly suggests that the PDNEC component develops during a classic adenoma-adenocarcinoma sequence.…”

“…This is frequent (40-80% depending on the location) when systematically studying neuroendocrine marker immunostaining in resected adenocarcinoma specimens [6,7,12] . It has no or uncertain prognostic influence, although a positive impact has been suggested in oesophageal adenocarcinoma [13] , whereas a negative one was evocated in gastric adenocarcinoma [15,16] , cholangiocarcinoma [17] , and colorectal adenocarcinoma [18,19] . Nevertheless, it does not yield therapeutic changes.…”

Benefit of rebiopsy for deciding treatment strategy in rectal cancer: A case report

“…Another possibility is that the adenocarcinoma changed into NEC subsequent to the initial diagnosis. One previous report has shown that neuroendocrine differentiation is more frequently observed in metastatic cancers compared with primary site tumors (9), whereas other reports have described cases wherein chemotherapy was shown to cause histological conversions (10,11). This phenomenon has also been observed in cases of prostate cancer and NSCLC, but the underlying mechanism is unknown (12).…”