Background. Previous reports demonstrated a positive modulation of neuroendocrine (NE) phenotype in rectal adenocarcinomas receiving neoadjuvant therapy prior to radical surgery. However, to our knowledge no data are available on the role of post surgical adjuvant therapy in determining NE differentiation in recurrent/metastatising colo-rectal carcinoma (CRC). Methods. We analysed 15 randomly selected cases of primary CRC (9 cases from colon and 6 from rectum) and the corresponding metastases (8 liver, 4 peritoneal and 3 lung) developed during tumor progression. These were resected 1 to 3 years following adjuvant chemotherapy (all cases) and radiotherapy (5 cases, all from the rectum). The presence of NE cells was evaluated by means of Chromogranin A (CgA) immunohistochemistry, which was scored on the basis on the percentage of neoplastic cells as follows: 0 (no cell staining), 1+ (1-20% positive tumor cells) and 2+ (more than 20% positive tumor cells). Results. In primary tumor samples, focal NE differentiation (CgA score 1+) was evident in 3/15 cases (2 colonic and 1 rectal). Two of these cases had predominant mucinous features. Metastatic tumors resected after adjuvant chemotherapy were stained in parallel, and found to contain CgA positive cells in 8/15 cases (1 of the three CgA positive primary CRC, and 7 additional cases that were negative in the primary tumor (4 from the colon and 3 from the rectum). Radiotherapy treated cases were not significantly correlated with an increased number of NE cells. The presence of NE phenotype was not correlated to clinical outcome, although the two patients with the highest number of endocrine cells in metastatic tissue (score 2) were both died of the disease. Conclusion. Our data support the hypothesis that adjuvant therapy might modulate the NE phenotype in CRC, possibly selecting a cell population less responsive to current therapeutic regimens for CRC with possible biological and prognostic implications.
INCREASED NUMBER OF NEUROENDOCRINE CELLS IN METASTATIC COLORECTAL ADENOCARCINOMA FOLLOWING CHEMO/RADIOTHERAPY
TAMPELLINI, MARCO;RIGHI, Luisella;VOLANTE, Marco;DOGLIOTTI, Luigi;PAPOTTI, Mauro Giulio;
2007-01-01
Abstract
Background. Previous reports demonstrated a positive modulation of neuroendocrine (NE) phenotype in rectal adenocarcinomas receiving neoadjuvant therapy prior to radical surgery. However, to our knowledge no data are available on the role of post surgical adjuvant therapy in determining NE differentiation in recurrent/metastatising colo-rectal carcinoma (CRC). Methods. We analysed 15 randomly selected cases of primary CRC (9 cases from colon and 6 from rectum) and the corresponding metastases (8 liver, 4 peritoneal and 3 lung) developed during tumor progression. These were resected 1 to 3 years following adjuvant chemotherapy (all cases) and radiotherapy (5 cases, all from the rectum). The presence of NE cells was evaluated by means of Chromogranin A (CgA) immunohistochemistry, which was scored on the basis on the percentage of neoplastic cells as follows: 0 (no cell staining), 1+ (1-20% positive tumor cells) and 2+ (more than 20% positive tumor cells). Results. In primary tumor samples, focal NE differentiation (CgA score 1+) was evident in 3/15 cases (2 colonic and 1 rectal). Two of these cases had predominant mucinous features. Metastatic tumors resected after adjuvant chemotherapy were stained in parallel, and found to contain CgA positive cells in 8/15 cases (1 of the three CgA positive primary CRC, and 7 additional cases that were negative in the primary tumor (4 from the colon and 3 from the rectum). Radiotherapy treated cases were not significantly correlated with an increased number of NE cells. The presence of NE phenotype was not correlated to clinical outcome, although the two patients with the highest number of endocrine cells in metastatic tissue (score 2) were both died of the disease. Conclusion. Our data support the hypothesis that adjuvant therapy might modulate the NE phenotype in CRC, possibly selecting a cell population less responsive to current therapeutic regimens for CRC with possible biological and prognostic implications.
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