Fetal haemopoiesis marking low-grade urinary bladder cancer

Abstract

Background: The immunohistochemical features of fetal haemoglobin cells and their distribution patterns in solid tumours, such as colorectal cancer and blastomas, suggest that fetal haemopoiesis may take place in these tumour tissues. These locally highly concentrated fetal haemoglobin (HbF) cells may promote tumour growth by providing a more efficient oxygen supply.

Methods and results: Biomarkers of HbF were checked in transitional cell carcinoma (TCC) of the urinary bladder, assessing this as a new parameter for disease management. Fetal haemoglobin was immunohistochemically examined in tumours from 60 patients with TCC of the bladder. Fetal haemoglobin erythrocytes and erythroblasts were mainly clonally distributed in proliferating blood vessels and not mixed with normal haemoglobin erythrocytes. The proportion of such HbF blood vessels could reach more than half of the total number of vessels. There were often many HbF erythroblasts distributed in one-cell or two-cell capillaries and present as 5-15% of cells in multi-cell vessels. This suggests a local proliferation of HbF-cell progenitors. Fetal haemoglobin cells were prominently marking lower grades of tumours, as 76% (n=21) of the patients with G1pTa were HbF+, whereas only 6.7% (n=30) of the patients with G3pT1-pT2a were HbF+.

Conclusion: Our results suggest that HbF, besides being a potential new marker for early tumour detection, might be an essential factor of early tumour development, as in fetal life. Inhibiting HbF upregulation may provide a therapeutic target for the inhibition of tumour growth.

Figure 1

Stages in proliferation of blood vessels with HbF cells in lamina propria of G1 TCC. Arrows indicating nucleated HbF progenitor cells: (A) clusters of HbF cells forming into fine vessels with many foci of nucleated HbF progenitor cells. (B) High density of small proliferating blood vessels. (C) Larger blood vessels spreading throughout the lamina propria.

Figure 2

Small capillary with two HbF erythroblasts.

Figure 3

Fetal haemoglobin cells, including nucleated (dark) cells, within tumour cells of G1 TCC.

Figure 4

Fetal haemoglobin cells including nucleated (dark) cells, within tumour cells of G2 TCC.

Figure 5

G3 TCC tumor with proliferating blood vessels (arrows) filled with normal Hb blood cells.