Time to Classify Tumours of the Stomach and the Kidneys According to Cell of Origin

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.

Clear Cell Renal Cancer, a Tumour with Neuroendocrine Features Originating from the Erythropoietin-Producing Cell

“…Considering the classification of kidney tumours in general, the continuous changes and additions of new types [13,14] indicate a weakness in the system and may suggest that the classifications are not rooted in biology. Our finding of erythropoietin and neuron-specific enolase expression in virtually all ccRCCs may indicate that the EPC is the cell of origin of ccRCC [2,3].…”

“…ccRCC may be accompanied by erythrocytosis which has been presumed to be due to production of erythropoietin (EPO) by the erythropoietin-producing cell (EPC) localised in the kidney. Some years ago, we showed that virtually all ccRCC cancer tumour cells expressed erythropoietin as well as the neuroendocrine marker neuronspecific enolase [2], which may suggest that the cell of origin of ccRCC is the EPC [3]. The present review is a follow-up further discussing the cell of origin of ccRCC.…”

ZNF92, an unexplored transcription factor with remarkably distinct breast cancer over-expression associated with prognosis and cell-of-origin

“…Consequently, the normal cell-of-origin epigenomic profile continues to shape the tumor phenotype through interactions with transforming genetic alterations 4 , 5 . It has been shown that cell-origin based classification of human tumors significantly improves the taxonomy and biological understanding of breast, ovarian, pancreatic, gastric, and kidney cancers, as well as melanoma, retinoblastoma, and lymphoma 6 – 15 .…”