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

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.

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368: The Cell of Origin of Clear Cell Renal Carcinoma - Re-Visited

The Journal of Urology ◽

10.1016/s0022-5347(18)32624-7 ◽

2006 ◽

Vol 175 (4S) ◽

pp. 120-121

Author(s):

Maxine G.B. Tran ◽

Miguel A. Esteban ◽

Deepa Shukla ◽

Ashish Chandra ◽

Tim S. O'Brien ◽

...

Keyword(s):

Renal Carcinoma ◽

Clear Cell ◽

Cell Of Origin ◽

Clear Cell Renal Carcinoma ◽

Cell Renal Carcinoma

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Types of Gastric Carcinomas

International Journal of Molecular Sciences ◽

10.3390/ijms19124109 ◽

2018 ◽

Vol 19 (12) ◽

pp. 4109 ◽

Cited By ~ 12

Author(s):

Helge Waldum ◽

Reidar Fossmark

Keyword(s):

Gastric Cancer ◽

Stem Cell ◽

Gastric Carcinogenesis ◽

Cell Of Origin ◽

Gastric Carcinomas ◽

Ecl Cell ◽

Cells Of Origin ◽

Increased Risk

Gastric cancer has reduced prevalence, but poor prognoses. To improve treatment, better knowledge of carcinogenesis and cells of origin should be sought. Stomach cancers are typically localized to one of the three mucosae; cardial, oxyntic and antral. Moreover, not only the stem cell, but the ECL cell may proliferate and give rise to tumours. According to Laurén, the classification of gastric carcinomas seems to reflect biological important differences and possible different cell of origin since the two subtypes, intestinal and diffuse, do not transform into the other and show different epidemiology. The stem cell probably gives rise to the intestinal type, whereas the ECL cell may be important in the diffuse type. Elevation of gastrin may be the carcinogenic factor for Helicobacter pylori as well as the recently described increased risk of gastric cancer due to proton pump inhibitor treatment. Therefore, it is essential to determine the role of the gastrin target cell, the ECL cell, in gastric carcinogenesis. Clinical trials with gastrin antagonists could improve prognoses in those with gastrin receptor positive tumours. However, further studies on gastric carcinomas applying relative available methods and with the highest sensitivity are warranted to improve our knowledge of gastric carcinogenesis.

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Clear cell renal carcinoma metastases to the pancreas

Perspectives in Surgery ◽

10.33699/pis.2020.99.7.311-315 ◽

2020 ◽

Vol 99 (7) ◽

Keyword(s):

Renal Carcinoma ◽

Clear Cell ◽

Average Length ◽

Malignant Tumour ◽

Malignant Tumours ◽

Clear Cell Renal Carcinoma ◽

Diagnostic Specificity ◽

Term Survival ◽

Contralateral Kidney ◽

Cell Renal Carcinoma

Introduction: To date, clear cell renal carcinoma (Grawitz tumour) remains the most frequent malignant tumour of the kidney in adults. It metastasises in more than 25% of cases, most frequently to the bones (osteolytic metastases), lungs, brain, liver, adrenal glands and the contralateral kidney. Metastases to the pancreas are rare and represent 1–4% of all malignant tumours of the pancreas. Methods: This is a retrospective analysis of patients who were operated at the Department of Surgery in Pilsen between 2010 and 2018 for histologically verified metastasis of clear cell carcinoma (Grawitz tumour) to the pancreas. Results: We operated 12 patients (8 men and 4 women). The metastases appeared on average 8 years and 8 months following the primary urological surgery. The mean age of the male patients was 66.5 years and that of the female patients was 67.4 years. In our sample, the diagnostic specificity of the CT scan was 50%, the diagnostic specificity of endoscopic ultrasound (EUS) was 75% and subsequen EUS-guided fine needle aspiration biopsy performed in 100% of cases yielded a specificity of 75%. Resectability was 92%. The average length of hospitalisation was 11.5 days. Post-operative complications according to Clavien-Dindo were grade 1 in 66%, grade 2 in 1.25% and grade 5 in 8.3% of the cases. The 30-day post-operative mortality was 8.3% (one patient). Conclusion: Clear cell renal carcinoma metastases to the pancreas are very rare. However, if radically removed, the patient has a good prognosis with regards to long-term survival.

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Acromegaly associated with GIST, non-small cell lung carcinoma, clear cell renal carcinoma, multiple myeloma, medulla oblongata tumour, adrenal adenoma, and follicular thyroid nodules

Endokrynologia Polska ◽

10.5603/ep.a2019.0005 ◽

2019 ◽

Vol 70 (2) ◽

pp. 213-217 ◽

Cited By ~ 2

Author(s):

Aleksandra Jawiarczyk-Przybyłowska ◽

Beata Wojtczak ◽

James Whitworth ◽

Krzysztof Sutkowski ◽

Martin Bidlingmaier ◽

...

Keyword(s):

Renal Carcinoma ◽

Thyroid Nodules ◽

Clear Cell ◽

Small Cell Lung Carcinoma ◽

Adrenal Adenoma ◽

Small Cell ◽

Clear Cell Renal Carcinoma ◽

Small Cell Lung ◽

Cell Lung Carcinoma ◽

Cell Renal Carcinoma

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Not only stem cells, but also mature cells, particularly neuroendocrine cells, may develop into tumours: time for a paradigm shift

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284818775054 ◽

2018 ◽

Vol 11 ◽

pp. 175628481877505 ◽

Cited By ~ 7

Author(s):

Helge L. Waldum ◽

Kjell Öberg ◽

Øystein F. Sørdal ◽

Arne K. Sandvik ◽

Bjørn I. Gustafsson ◽

...

Keyword(s):

Stem Cells ◽

Neuroendocrine Tumours ◽

Neuroendocrine Cells ◽

Cell Of Origin ◽

Malignant Tumours ◽

Cellular Origin ◽

Degree Of Malignancy ◽

Benign Tumours

Stem cells are considered the origin of neoplasms in general, and malignant tumours in particular, and the stage at which the stem cells stop their differentiation determines the degree of malignancy. However, there is increasing evidence supporting an alternative paradigm. Tumours may develop by dedifferentiation from mature cells able to proliferate. Studies of gastric carcinogenesis demonstrate that mature neuroendocrine (NE) cells upon long-term overstimulation may develop through stages of hyperplasia, dysplasia, and rather benign tumours, into highly malignant carcinomas. Dedifferentiation of cells may change the histological appearance and impede the identification of the cellular origin, as seen with gastric carcinomas, which in many cases are dedifferentiated neuroendocrine tumours. Finding the cell of origin is important to identify risk factors for cancer, prevent tumour development, and tailor treatment. In the present review, we focus not only on gastric tumours, but also evaluate the role of neuroendocrine cells in tumourigenesis in two other foregut-derived organs, the lungs and the pancreas, as well as in the midgut-derived small intestine.

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Correct Identification of Cell of Origin May Explain Many Aspects of Cancer: The Role of Neuroendocrine Cells as Exemplified from the Stomach

International Journal of Molecular Sciences ◽

10.3390/ijms21165751 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5751 ◽

Cited By ~ 1

Author(s):

Helge Waldum ◽

Patricia G. Mjønes

Keyword(s):

Growth Regulation ◽

Late Recurrence ◽

Neuroendocrine Cells ◽

Correct Identification ◽

Cell Of Origin ◽

Proliferating Cells ◽

Differentiated Cells ◽

Ecl Cell

Cancers are believed to originate from stem cells. Previously, the hypothesis was that tumors developed due to dedifferentiation of mature cells. We studied the regulation of gastric acid secretion and showed that gastrin through the gastrin receptor stimulates enterochromaffin-like (ECL) cell histamine release and proliferation. In animal and human studies, we and others showed that long-term hypergastrinemia results in ECL cell-derived tumor through a sequence of hyperplasia, dysplasia, neuroendocrine tumors (NETs), and possibly neuroendocrine carcinomas (NECs) and adenocarcinomas of diffuse type. Perhaps, other cancers may also have their origin in differentiated cells. Knowledge of the growth regulation of the cell of origin is important in cancer prophylaxis and treatment. Physiology plays a central role in carcinogenesis through hormones and other growth factors. Every cell division implies a small risk of mutation; thus mitogens are also mutagens. Moreover, metastasis of slow proliferating cells may also explain so-called tumor dormancy and late recurrence.

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1651: Molecular Prognostic Modeling Using Protein Expression Profile in Clear Cell Renal Carcinoma

The Journal of Urology ◽

10.1016/s0022-5347(18)38859-1 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 436-436 ◽

Cited By ~ 3

Author(s):

Hyung L. Kim ◽

David B. Seligson ◽

Nicolette Janzen ◽

Matthew H. Bui ◽

Robert A. Figlin ◽

...

Keyword(s):

Protein Expression ◽

Expression Profile ◽

Renal Carcinoma ◽

Clear Cell ◽

Clear Cell Renal Carcinoma ◽

Protein Expression Profile ◽

Cell Renal Carcinoma ◽

Prognostic Modeling

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Tumor Classification Should Be Based on Biology and Not Consensus: Re-Defining Tumors Based on Biology May Accelerate Progress, An Experience of Gastric Cancer

Cancers ◽

10.3390/cancers13133159 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3159

Author(s):

Helge Waldum

Keyword(s):

Gastric Cancer ◽

Malignant Tumors ◽

Growth Control ◽

Neuroendocrine Differentiation ◽

Diffuse Type ◽

Cell Of Origin ◽

Genetic Changes ◽

Ecl Cell ◽

Neuroendocrine Carcinomas ◽

Complete Carcinogens

Malignant tumors are a consequence of genetic changes mainly occurring during cell division, sometimes with a congenital component. Therefore, accelerated cell divisions will necessarily predispose individuals, whether due to conditions of chronic cell destruction or hormonal overstimulation. It has been postulated that two genetic hits are necessary for the development of malignancy (Knudson). The correct view is probably that the number of genetic changes needed depends on the role the mutated genes have in proliferation and growth control. Hormones should accordingly be regarded as complete carcinogens. In this review based upon experience of gastric cancer where gastrin is central in the pathogenesis, it is argued that oxyntic atrophy—and not metaplasia as postulated by Correa—is the central precancer change in gastric mucosa. Moreover, the target cell of gastrin, the enterochromaffin-like (ECL) cell, is central in gastric carcinogenesis and most probably the cell of origin of gastric carcinomas of the diffuse type according to Lauren (a classification probable in accordance with biology). The distinction between adenocarcinomas and neuroendocrine carcinomas based upon a certain percentage of cancer cells with neuroendocrine differentiation is questioned. To make progress in the treatment of cancer, a correct classification system and knowledge of the pathogenesis are necessary.

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