Endocrine cells and prognosis in patients with colorectal carcinoma

Abstract

Using chromogranin (CG) immunohistochemical staining, the prognostic significance of endocrine differentiation was investigated in 212 patients with primary colorectal adenocarcinoma (including 6 patients with mucosal carcinoma). CG‐immunoreactive cells were found to be an integral component of the tumor in 67 of 206 patients (32.5%, excluding mucosal carcinoma). The intra‐cellular localization of CG in the CG‐immunoreactive cells in cancer tissue was completely different from that in the normal endocrine cells of the large bowel. In addition, morphologic changes such as nuclear hyperchromasia and pleomorphism also indicated that the CG‐immunoreactive cells in the cancer tissue were malignant. The tumors were divided into three groups based on the frequency of CG‐immunoreactive cells: Group I (n = 139), negative; Group II (n = 38), less than 1 positive cell/mm2; and Group III (n = 29), more than 1 positive cell/mm2. No correlation was observed between CG‐immunoreactivity (CG‐IR) and tumor location, grade, depth of invasion, or stage, regardless of lymph node involvement. However, patients with numerous endocrine tumor cells (Group III) had a significantly worse prognosis compared with patients without endocrine cells (Group I) (multivariate Cox's model, P < 0.01). Similar findings were observed in patients with node‐negative tumor (multivariate Cox's model, P < 0.05). These results indicated that the neuroendocrine differentiation is an independent prognostic factor and that CG‐immunohistochemistry is useful for detecting a subgroup with a worse prognosis among patients with colorectal cancer.

Increased neuroendocrine cells in resected metastases compared to primary colorectal adenocarcinomas

“…In the present series, cases having a neuroendocrine differentiated component in the primary tumors had a slightly shorter survival both from the time of diagnosis and the time from metastatic spread but statistical significance was reached for the latter case only, possible due to the relatively small sample size. Other literature data are in line with this observation [13,19,20], although some authors found no prognostic differences between neuroendocrine differentiated and conventional colorectal carcinoma [21]. No correlation was also observed with any clinical pathological parameter.…”

Prevalence and Prognostic Significance of Neuroendocrine Cells in Esophageal Adenocarcinoma

“…Carcinomas that display diffuse neuroendocrine differentiation are relatively rare, however, compared with otherwise typical adenocarcinomas that contain scattered tumor cells showing neuroendocrine differentiation. Such adenocarcinomas of the colon have been the subject of several relatively large studies (1)(2)(3)(4)(5). Most of these studies found that the presence of these scattered tumor neuroendocrine cells had no detectable influence on stage or prognosis and no association with tumor grade (2)(3)(4).…”

“…Probably the most common pattern of neuroendocrine differentiation in GI neoplasms, however, is the presence of scattered tumor cells showing neuroendocrine differentiation in an otherwise typical adenocarcinoma. The presence of neuroendocrine cells in colonic adenocarcinomas (1)(2)(3)(4)(5) and gastric adenocarcinomas (6) has long been recognized. Although up to 42% of typical colon adenocarcinomas contain scattered chromogranin (CG)-positive cells (4), this finding does not seem to influence prognosis, and these tumors are not classified as mixed adenocarcinoma/ neuroendocrine tumors.…”

Neuroendocrine cells in tumour growth of the prostate.

“…Another possibility is that most neuroendocrine differentiated tumours are hormone resistant or are characterized by relapse after hormonal treatment (Dauge & Delmas 1986, Tetu et al 1987, Abrahamsson et al 1989, Cohen et al 1990. In some malignancies, neuroendocrine differentiation has been shown to have certain prognostic value, such as somatostatin in medullary thyroid carcinoma (Modigliani et al 1990), hCG (Yamagushi et al 1989), and chromogranin A (Hamada et al 1992) in colorectal cancer, and PTHrP in breast cancer (Vargas et al 1992). However, evidence of the prognostic implications of neuroendocrine differentiation in conventional prostatic adenocarcinoma is contradictory, with some earlier studies suggesting that there is a strong correlation between neuroendocrine differentiation and prognosis (Abrahamsson et al 1989, Cohen et al 1990, di Sant'Agnese 1993), whereas others have failed to demonstrate such a correlation (de Matteis 1992, Aprikian et al 1993, Paul et al 1993.…”