Molecular Biology Reports

, Volume 46, Issue 2, pp 2147–2152 | Cite as

Angiogenic regeneration defines loco-regional recurrence following pre-operative radio-chemotherapy for rectal cancer: a pilot study

  • Michael I. KoukourakisEmail author
  • Ioannis M. Koukourakis
  • Stella Arelaki
  • Maria Kouroupi
  • Spyros Domoxoudis
  • Alexandra Giatromanolaki
Original Article


Previous studies from our group have brought forward the concept of angiogenic regeneration during radiotherapy (RT), as a major cause of RT failure. This process was examined herein in rectal cancer patients undergoing preoperative chemo-radiotherapy. Out of 25 patients with stage II/III rectal adenocarcinoma, 15 had incomplete response (pIR) after preoperative chemo-radiotherapy. The MIB1 proliferation index, the vascular density (VD) assessed with the anti-CD31 antibody and the Hypoxia Inducible Factor HIF1α was assessed. High VD before RT was related with poor local relapse free survival LRFS (p = 0.04), in cases with pIR. Pre-RT values of MIB1 and of HIF1α were not related with LRFS. High MIB1 index and intensification of VD beyond pre-treatment levels in post-RT samples, features indicative of angiogenic regeneration, defined poor LRFS (p = 0.04 and p = 0.0008, respectively). Angiogenic regeneration is strongly related to failure of RT and surgery to control loco-regional disease in rectal cancer patients. Addition of anti-angiogenic agents in the preoperative chemo-radiotherapy regimens may prove beneficial in subgroups of patients.


Rectal cancer MIB1 index Vascular density HIF1α Angiogenic regeneration 



The study has been financially supported by the Tumour and Angiogenesis Research Group (Grant No. 0017).

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest to report.

Supplementary material

11033_2019_4668_MOESM1_ESM.tif (132 kb)
Supplementary material 1 (TIF 132 KB). Supplemental Figure 1s MIB1 score in patients with pIR and intensified angiogenic activity (VD intensified) in post-radiotherapy biopsies vs. in patients without angiogenic intensification (VD stable)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department Radiotherapy/OncologyDemocritus University of ThraceAlexandroupolisGreece
  2. 2.Department of PathologyDemocritus University of ThraceAlexandroupolisGreece

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