Abstract
Malignant tumours are traditionally classified according to their organ of origin and whether they are of epithelial (carcinomas) or mesenchymal (sarcomas) origin. By histological appearance the site of origin may often be confirmed. Using same treatment for tumours from the same organ is rational only when there is no principal heterogeneity between the tumours of that organ. Organ tumour heterogeneity is typical for the lungs with small cell and non-small cell tumours, for the kidneys where clear cell renal carcinoma (CCRCC) is the dominating type among other subgroups, and in the stomach with adenocarcinomas of intestinal and diffuse types. In addition, a separate type of neuroendocrine tumours (NETs) is found in most organs. Every cell type able to divide may develop into a tumour, and the different subtypes most often reflect different cell origin. In this article the focus is on the cells of origin in tumours arising in the stomach and kidneys and the close relationship between normal neuroendocrine cells and NETs. Furthermore, that the erythropoietin producing cell may be the cell of origin of CCRCC (a cancer with many similarities to NETs), and that gastric carcinomas of diffuse type may originate from the ECL cell, whereas the endodermal stem cell most probably gives rise to cancers of intestinal type.
Highlights
Tumours were initially classified macroscopically according to the organ where they appeared
The specificity of a marker may be underestimated as we showed for neuron specific enolase (NSE) which had been claimed to be rather unspecific neuron-specific enolase (NSE) positive tumours have been shown to be increasingly positive for other neuroendocrine (NE) markers when increasing the sensitivity of the methods and/or increasing the number of NE markers used [64]
Based upon histochemistry [53], immunohistochemistry [54], immunoelectron microscopy [59] and in-situ hybridization [56,57] we have repeatedly shown that enterochromaffin like (ECL) cell markers are mainly expressed in carcinomas of diffuse type, and we have concluded that these carcinomas originate from the ECL cell [53,54,78]
Summary
Tumours were initially classified macroscopically according to the organ where they appeared. Tumours were early recognized to spread from one organ to another by metastasis, and in such situations histological differences between the tumours became useful to determine their organ of origin. This organ classification of neoplasia still prevails and is used to select treatment. From a biological point of view this may be a rational approach if there is no heterogeneity in cellular origin of tumours from the actual organ. This is not the case, since many cell types in an organ are able to divide and give rise to tumours. In the present review we will discuss tumour classification with respect to tumour biology, including the cells of origin
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