Endocrine differentiation of gastric adenocarcinoma. The prevalence as evaluated by immunoreactive chromogranin a and its biologic significance

Abstract

The prevalence of endocrine differentiation of conventional gastric adenocarcinoma was evaluated on the 212 cases (including 62 mucosal carcinomas) of consecutively resected stomach for adenocarcinoma in our hospital using anti-chromogranin A (CGA) antibodies. CGA-positive cells were found in 28 of 150 cases (18.7%) as an integral tumor component. In immunocytochemistry and electron microscopic examinations, we could classify these 28 cases into three groups according to the distribution patterns of CGA-positive cells. The first group consisted of 12 cases in which scattered CGA-positive cells were located in neoplastic glands. The second group consisted of six cases of scirrhous carcinoma in which CGA-positive cells were separated by fibrovascular tissue. The third group consisted of ten cases in which the positive cells were present in clusters. No definite correlation was recognized between the appearance of CGA cells and histologic types of predominance. In the analysis of the hormonal substances coexpressed by CGA-positive cells, immunoreactive serotonin (SER) was found most frequently, and somatostatin (SS), gastrin (GAS), glucagon/glicentin (GLU/GLI), and peptide-tyrosine-tyrosine (PYY) like immunoreactivities were found in a few tumor cells. CGA-positive cells occupied limited parts of the tumors in most cases, and they were noticeably more frequent in advanced stage cases. This might explain why endocrine differentiation reflects the dysexpression of the neoplastic stem cells. Furthermore, absence of mitotic figures in this type of cell and negativity of a single colony composed exclusively of CGA cells in metastatic foci suggested that these cells are in a dormant phase and are probably postmitotic.

Genetic evidence for the multi-step progression of mixed glandular–neuroendocrine gastric carcinomas

“…These results are compatible with the previous immunohistochemical findings on poorly differentiated neuroendocrine carcinomas of the extrapulmonary sites, such as stomach [9], intestines [33], and vagina [28]. Chromogranin A-positive cells (cases 1 and 2) and neuron-specific enolase-and synaptophysin-positive cells (case 1) were found in the glandular component of a mixed gastric tumor (Table 2), which is in agreement with previous reports [12,22,25,27] showing that neuroendocrine differentiation is dispersed in an ordinary gastric carcinoma. In the true composite tumor case 1 containing a large glandular component, two adenocarcinoma sites that were microdissected according to the presence (Fig.…”

“…This correlation between incomplete LOHs and scattered neuroendocrine differentiation suggests that neuroendocrine cells containing primary LOHs serve as precursors for neuroendocrine carcinomas. However, in previous studies, neuroendocrine cells dispersed throughout adenocarcinomas of the stomach were found to be quiescent with no mitosis [12,22]. Such neuroendocrine cells were thought to be a fortuitous, non-proliferative outcome of multipotential, mitotic tumor cells.…”

“…Neuroendocrine differentiation is dispersed in epithelial tumor cell populations with an estimated frequency ranging from 3% to 34%, depending on the immunohistochemical markers used and the number of specimens examined [12,22,27,30]. In some cases, the neuroendocrine cells occupy the main part of a gastric tumor lesion and an adenocarcinoma is localized in a small portion [2,16].…”

Neuroendocrine-like differentiation in patients with pancreatic carcinoma

“…NED also has been observed in patients with carcinoma of different organs, such as the lung, breast, stomach, liver, colon, and prostate. [15][16][17][18][19][20][21][22] Little is known about the clinical significance of NED in patients with those malignancies, except for patients with small cell lung carcinoma, in whom NCAM as a marker for NED indicates a poorer prognosis, to any of the following: duodenum, bile duct, peripancreatic tissues, without lymph node metastasis; Stage III: tumors with regional lymph node metastasis; Stage IVa: tumor extends directly to any of the following: stomach, spleen, colon, adjacent large vessels, with or without regional lymph node metastasis; Stage IVb: metastasis to lymph nodes beyond the regional level or distant organ metastasis (9). b Curability A: absolute cure with lymph node dissection (D) Ͼ lymph node metastasis (N); curability B: relative cure with D ϭ N; curability C: definite residual tumor in surgical margin (8).…”

The prevalence and clinical significance of chromogranin A and secretogranin II immunoreactivity in colorectal adenocarcinomas

“…The presence of cells containing secretory granules of endocrine type in carcinomas arising in the gastrointestinal tract has been documented convincingly using argyrophil stains [2,18,23,32,36] and, more recently, by the immunocytochemical demonstration of the presence of specific endocrine markers [1,4,9,13,15,19,27,28]. The occurrence of endocrine cells in noncarcinoid carcinomas of the gastrointestinal tract, however, initially generated controversies about the origin of these cells.…”