Vascular architecture, hypoxia, and proliferation in first-generation xenografts of human head-and-neck squamous cell carcinomas.
OBJECTIVE
To quantify the physiologic status of human tumor cells in relation to the tumor vasculature.


METHODS
Fourteen tumors of 11 first-generation xenograft lines of human head-and-neck squamous cell carcinoma were injected with the hypoxic cell marker pimonidazole, the proliferation marker BrdUrd, and the perfusion marker Hoechst 33342. Consecutive tissue sections were processed with immunohistochemical methods and analyzed with image-analysis techniques.


RESULTS
Three different hypoxic patterns were found: patchy, ribbon-like, and mixed. An image-analysis method was developed to quantify these, and an elongation index (length/width) was calculated for hypoxia. The mean elongation indices ranged from 2.0 to 28.3 and showed a good correlation with the visual scoring of hypoxic patterns. Comparative analysis of hypoxic and proliferating cells in zones around the tumor vasculature showed the presence of both hypoxic and proliferating cells in all zones up to 250 microm from the vessels. The largest coexistence of hypoxic and proliferating cells seemed to occur at 50-100 microm from the vessels.


CONCLUSIONS
The three hypoxic patterns could be quantified by an elongation index, which is an additional parameter that allows distinction of tumors with similar fractions of hypoxic cells. The analysis of hypoxic and proliferating cells as a function of distance from the tumor vasculature indicates that proliferation does occur also at low oxygen tensions.
Department of Radiation Oncology, University Medical Center Nijmegen, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands. A.Ljungkvist@rther.umcn.nl
Anna S E
AS
Ljungkvist
Johan
J
Bussink
Paulus F J W
PF
Rijken
Johannes H A M
JH
Kaanders
Albert J
AJ
van der Kogel
Juliana
J
Denekamp
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D015687:Cell Hypoxia; D006258:Head and Neck Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D001973:Bromodeoxyuridine