Journal Article
. 2020 Aug; 2020:3818051.
doi: 10.1155/2020/3818051.

Morphological Characteristics and Clinical Significance of Different Types of Tumor Vessels in Patients with Stages I-IIA of Squamous Cervical Cancer

Marina A Senchukova 1 Elena V Makarova 1 Elena I Shurygina 2 Nadezhda N Volchenko 3 
  • PMID: 32849870
  •     70 References


The determination of factors associated with progression of cervical cancer is important, both for a recurrence risk assessment and for determining optimal treatment tactics. Previously, we showed the prognostic value of different types of tumor microvessels (MVs) in gastric and breast cancer. The object of this research was to study the morphology and clinical significance of different tumor microvessels in early cervical cancer. A total of 65 archived paraffin blocks of patients with I-IIA stages of squamous cervical cancer were investigated. Samples were stained with Mayer hematoxylin and immunohistochemically using antibodies to CD34, podoplanin, HIF-1a, and Snail. The eight types of tumor MVs differed in morphology were identified. It was established that only the dilated capillaries (DСs) with weak expression of CD34, the contact type DCs, the capillaries in tumor solid component, and the lymphatic vessels in the lymphoid and polymorphic cell infiltrates of tumor stroma are associated with clinical and pathological characteristics of early cervical cancer. Preliminary results also suggest that a combination of fragmentation in tumor solid component and the contact type DCs may predict a recurrence of early cervical cancer. Given the small number of cervical cancer recurrences, the predictive significance of the described markers requires a more thorough examination.

Prognostic factors in Asian and white American patients with cervical cancer, considering competing risks.
Y Hou, S Guo, +4 authors, Z Chen.
Curr Oncol, 2019 Jul 10; 26(3). PMID: 31285669    Free PMC article.
Targeting the tumor microenvironment: focus on angiogenesis.
Fengjuan Fan, Alexander Schimming, Dirk Jaeger, Klaus Podar.
J Oncol, 2011 Aug 31; 2012. PMID: 21876693    Free PMC article.
Hypoxia-inducible proteins HIF1α and lactate dehydrogenase LDH5, key markers of anaerobic metabolism, relate with stem cell markers and poor post-radiotherapy outcome in bladder cancer.
Michael I Koukourakis, Christos Kakouratos, +4 authors, Alexandra Giatromanolaki.
Int J Radiat Biol, 2016 Mar 25; 92(7). PMID: 27010533
Hypoxia induces endothelial‑mesenchymal transition in pulmonary vascular remodeling.
Bo Zhang, Wen Niu, +3 authors, Zhi-Chao Li.
Int J Mol Med, 2018 Mar 24; 42(1). PMID: 29568878    Free PMC article.
High expression of HIF-2α and its anti-radiotherapy effect in lung cancer stem cells.
J C Sun, F He, +5 authors, D L Niu.
Genet Mol Res, 2016 Jan 20; 14(4). PMID: 26782458
Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis.
Marc Arbyn, Elisabete Weiderpass, +4 authors, Freddie Bray.
Lancet Glob Health, 2019 Dec 10; 8(2). PMID: 31812369    Free PMC article.
Highly Cited.
Elevated expression of thymosin β4, vascular endothelial growth factor (VEGF), and hypoxia inducible factor (HIF)-1α in early-stage cervical cancers.
Nam Soo Kim, Yun-Jeong Kang, +6 authors, Hee-Jae Cha.
Pathol Oncol Res, 2011 Jan 08; 17(3). PMID: 21213129
The association between aquaporin-1 expression, microvessel density and the clinicopathological features of hepatocellular carcinoma.
Li-Min Luo, Hu Xia, +3 authors, Min Wei.
Oncol Lett, 2018 Jan 19; 14(6). PMID: 29344137    Free PMC article.
Correlation between matrix metalloproteinase-9 and vascular endothelial growth factor expression in lung adenocarcinoma.
Y L Wen, L Li.
Genet Mol Res, 2016 Jan 20; 14(4). PMID: 26782587
Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases.
Peter Carmeliet, Rakesh K Jain.
Nat Rev Drug Discov, 2011 Jun 02; 10(6). PMID: 21629292
Highly Cited. Review.
Enhancing prognosis prediction using pre-treatment nodal SUVmax and HPV status in cervical squamous cell carcinoma.
Chae Moon Hong, Shin-Hyung Park, +6 authors, Shin Young Jeong.
Cancer Imaging, 2019 Jun 27; 19(1). PMID: 31234933    Free PMC article.
Neoadjuvant brachytherapy and chemotherapy followed by radical surgery for stage IB2 and IIA cervical cancer: A retrospective comparison with chemoirradiation.
Yaomei Ma, Guiling Zhao, +4 authors, Karen K L Chan.
Mol Clin Oncol, 2018 Mar 21; 8(4). PMID: 29556393    Free PMC article.
Retrospective analysis for predictors of parametrial involvement in IB cervical cancer.
Satoshi Kubota, Eiji Kobayashi, +4 authors, Tadashi Kimura.
J Obstet Gynaecol Res, 2018 Dec 20; 45(3). PMID: 30565810
Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours.
P B Vermeulen, G Gasparini, +10 authors, L Y Dirix.
Eur J Cancer, 2002 Jul 27; 38(12). PMID: 12142044
Highly Cited. Review.
Vessel co-option in cancer.
Elizabeth A Kuczynski, Peter B Vermeulen, +2 authors, Andrew R Reynolds.
Nat Rev Clin Oncol, 2019 Mar 01; 16(8). PMID: 30816337
Highly Cited. Review.
Tumour blood vessel normalisation by prolyl hydroxylase inhibitor repaired sensitivity to chemotherapy in a tumour mouse model.
Satoshi Koyama, Shinji Matsunaga, +4 authors, Shuhei Tomita.
Sci Rep, 2017 Apr 01; 7. PMID: 28361934    Free PMC article.
Ancestral vascular lumen formation via basal cell surfaces.
Tomás Kucera, Boris Strilić, +3 authors, Eckhard Lammert.
PLoS One, 2009 Jan 07; 4(1). PMID: 19125185    Free PMC article.
Significance of CD34 Negative Hematopoietic Stem Cells and CD34 Positive Mesenchymal Stem Cells - A Valuable Dimension to the Current Understanding.
Chandra Viswanathan, Rohit Kulkarni, Abhijit Bopardikar, Sushilkumar Ramdasi.
Curr Stem Cell Res Ther, 2017 May 04; 12(6). PMID: 28464788
Early Actions of Anti-Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor Drugs on Angiogenic Blood Vessels.
Basel Sitohy, Sunghee Chang, +9 authors, Harold F Dvorak.
Am J Pathol, 2017 Jul 25; 187(10). PMID: 28736316    Free PMC article.
Outcome and prognostic factors in cervical cancer patients treated with surgery and concurrent chemoradiotherapy: a retrospective study.
Yan-Mei Liu, Ling-Qin Ni, +3 authors, Shen-Peng Ying.
World J Surg Oncol, 2018 Jan 31; 16(1). PMID: 29378625    Free PMC article.
Risk stratification models for para-aortic lymph node metastasis and recurrence in stage IB-IIB cervical cancer.
Koji Matsuo, Muneaki Shimada, +7 authors, Toru Sugiyama.
J Gynecol Oncol, 2017 Dec 01; 29(1). PMID: 29185269    Free PMC article.
Different types of tumor vessels in breast cancer: morphology and clinical value.
Marina A Senchukova, Natalia V Nikitenko, +2 authors, Alexander A Stadnikov.
Springerplus, 2015 Sep 26; 4. PMID: 26405632    Free PMC article.
Tumor Stroma, Tumor Blood Vessels, and Antiangiogenesis Therapy.
Harold F Dvorak.
Cancer J, 2015 Jul 30; 21(4). PMID: 26222073
UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1α.
Yoko Goto, Lihua Zeng, +18 authors, Hiroshi Harada.
Nat Commun, 2015 Jan 24; 6. PMID: 25615526    Free PMC article.
Highly Cited.
Integrin-mediated cell-matrix interaction in physiological and pathological blood vessel formation.
Stephan Niland, Johannes A Eble.
J Oncol, 2011 Sep 24; 2012. PMID: 21941547    Free PMC article.
Surgical treatment of microinvasive cervical cancer: analysis of pathologic features with implications on radicality.
Juliana Yoko Yoneda, Joana Froes Braganca, +3 authors, Luiz Carlos Zeferino.
Int J Gynecol Cancer, 2015 Mar 06; 25(4). PMID: 25742569
The role of lymphangiogenesis and angiogenesis in tumor metastasis.
Roman Paduch.
Cell Oncol (Dordr), 2016 Apr 30; 39(5). PMID: 27126599    Free PMC article.
Highly Cited. Review.
Patient-specific organotypic blood vessels as an in vitro model for anti-angiogenic drug response testing in renal cell carcinoma.
José A Jiménez-Torres, María Virumbrales-Muñoz, +3 authors, David J Beebe.
EBioMedicine, 2019 Mar 25; 42. PMID: 30902740    Free PMC article.
Comparison of adjuvant therapy for node-positive clinical stage IB-IIB cervical cancer: Systemic chemotherapy versus pelvic irradiation.
Koji Matsuo, Muneaki Shimada, +6 authors, Toru Sugiyama.
Int J Cancer, 2017 May 20; 141(5). PMID: 28524247    Free PMC article.
Randomized study between radical surgery and radiotherapy for the treatment of stage IB-IIA cervical cancer: 20-year update.
Fabio Landoni, Alessandro Colombo, +3 authors, Costantino Mangioni.
J Gynecol Oncol, 2017 Apr 07; 28(3). PMID: 28382797    Free PMC article.
Adjuvant chemotherapy versus concurrent chemoradiotherapy for high-risk cervical cancer after radical hysterectomy and systematic lymphadenectomy.
Munetaka Takekuma, Yuka Kasamatsu, +5 authors, Yasuyuki Hirashima.
Int J Clin Oncol, 2016 Feb 10; 21(4). PMID: 26857458
Unraveling the Role of Angiogenesis in Cancer Ecosystems.
Iratxe Zuazo-Gaztelu, Oriol Casanovas.
Front Oncol, 2018 Jul 18; 8. PMID: 30013950    Free PMC article.
Highly Cited. Review.
Quantifying tumour vascularity in non-luminal breast cancers.
Maria Ryssdal Kraby, Signe Opdahl, Lars A Akslen, Anna M Bofin.
J Clin Pathol, 2017 Mar 03; 70(9). PMID: 28249942
Early hematological effects of chemo-radiation therapy in cancer patients and their pattern of recovery - A prospective single institution study.
H N Lee, M K Mahajan, +2 authors, M S Tiwana.
Gulf J Oncolog, 2015 Feb 16; 1(17). PMID: 25682452
Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods.
J Ferlay, M Colombet, +5 authors, F Bray.
Int J Cancer, 2018 Oct 24; 144(8). PMID: 30350310
Highly Cited.
Prognostic value of microvessel density in cervical cancer.
Xiaoli Hu, Hailing Liu, Miaomiao Ye, Xueqiong Zhu.
Cancer Cell Int, 2018 Oct 12; 18. PMID: 30305802    Free PMC article.
Urinary Dysfunction Assessment in Long-Term Survivors of Carcinoma Cervix Using LENT SOMA Scale: An Indian Study Addressing Quality of Life Issues
Abhishek Shankar, Jaineet Patil, +6 authors, Goura Kishor Rath.
Asian Pac J Cancer Prev, 2019 Feb 26; 20(2). PMID: 30803196    Free PMC article.
A study of treatments and outcomes in elderly women with cervical cancer.
Kumi Shimamoto, Toshiaki Saito, +5 authors, Masao Okadome.
Eur J Obstet Gynecol Reprod Biol, 2018 Jul 01; 228. PMID: 29960201
Hypoxia-inducible factor 1-mediated characteristic features of cancer cells for tumor radioresistance.
Hiroshi Harada.
J Radiat Res, 2016 Mar 18; 57 Suppl 1. PMID: 26983985    Free PMC article.
The extent of retraction clefts correlates with lymphatic vessel density and VEGF-C expression and predicts nodal metastasis and poor prognosis in early-stage breast carcinoma.
Geza Acs, Gyorgy Paragh, +2 authors, Paul J Zhang.
Mod Pathol, 2011 Oct 25; 25(2). PMID: 22020194
Twenty years after: the beautiful hypothesis and the ugly facts.
Francesco Pezzella, Kevin Gatter, Chao-Nan Qian.
Chin J Cancer, 2016 Feb 26; 35. PMID: 26911137    Free PMC article.
Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma.
Iris Helfrich, Inka Scheffrahn, +7 authors, Dirk Schadendorf.
J Exp Med, 2010 Mar 03; 207(3). PMID: 20194633    Free PMC article.
The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy.
Barbara Muz, Pilar de la Puente, Feda Azab, Abdel Kareem Azab.
Hypoxia (Auckl), 2016 Oct 25; 3. PMID: 27774485    Free PMC article.
Highly Cited. Review.
CANCER. Tumor angiogenesis, from foe to friend.
Lee B Rivera, Gabriele Bergers.
Science, 2015 Aug 15; 349(6249). PMID: 26273044
The expression and underlying angiogenesis effect of DPC4 and VEGF on the progression of cervical carcinoma.
Yanni A, Ying Li, Shuping Zhao.
Oncol Lett, 2018 Feb 13; 15(2). PMID: 29434970    Free PMC article.
Correlation between the progression of cancer and the expression of matrix metalloproteinase-9 in metastatic spinal tumor.
Bolong Zheng, Dingjun Hao, Hua Guo, Baorong He.
J BUON, 2018 Dec 21; 23(5). PMID: 30570882
Assessement of angiogenesis reveals blood vessel heterogeneity in lung carcinoma.
Amalia Birau, Raluca Amalia Ceausu, +3 authors, Teodora Olariu.
Oncol Lett, 2012 Dec 04; 4(6). PMID: 23205116    Free PMC article.
Survival of women with microinvasive adenocarcinoma of the cervix is not improved by radical surgery.
Lisa M Bean, Kristy K Ward, Steven C Plaxe, Michael T McHale.
Am J Obstet Gynecol, 2017 May 20; 217(3). PMID: 28522318
Prognostic role of vascular endothelial growth factor in cervical cancer: a meta-analysis.
Jing Zhang, Jiaming Liu, +6 authors, Xuelei Ma.
Oncotarget, 2017 Feb 09; 8(15). PMID: 28177889    Free PMC article.
Postoperative pelvic intensity-modulated radiation therapy reduced the incidence of late gastrointestinal complications for uterine cervical cancer patients.
Keisuke Tsuchida, Naoya Murakami, +9 authors, Jun Itami.
J Radiat Res, 2019 Jun 30; 60(5). PMID: 31251358    Free PMC article.
Perineural invasion as a prognostic risk factor in patients with early cervical cancer.
Mei Tang, Qiuli Liu, +4 authors, Yuan Wang.
Oncol Lett, 2019 Jan 19; 17(1). PMID: 30655871    Free PMC article.
Fact or Fiction, It Is Time for a Verdict on Vasculogenic Mimicry?
Andrés Valdivia, Gabriel Mingo, +7 authors, Gareth I Owen.
Front Oncol, 2019 Aug 21; 9. PMID: 31428573    Free PMC article.
Revisiting tumor angiogenesis: vessel co-option, vessel remodeling, and cancer cell-derived vasculature formation.
Chao-Nan Qian, Min-Han Tan, Jun-Ping Yang, Yun Cao.
Chin J Cancer, 2016 Jan 10; 35. PMID: 26747273    Free PMC article.
Heterogeneity of hypoxia in solid tumours and mechanochemical reactions with oxygen nanobubbles.
V B Orel, M A Zabolotny, V E Orel.
Med Hypotheses, 2017 May 10; 102. PMID: 28478838
Markers of angiogenesis in high-risk, early-stage cervical cancer: A Gynecologic Oncology Group study.
Leslie M Randall, Bradley J Monk, +6 authors, John P Fruehauf.
Gynecol Oncol, 2008 Dec 27; 112(3). PMID: 19110305    Free PMC article.
Global cancer statistics, 2012.
Lindsey A Torre, Freddie Bray, +3 authors, Ahmedin Jemal.
CA Cancer J Clin, 2015 Feb 06; 65(2). PMID: 25651787
Highly Cited.
Replacement and desmoplastic histopathological growth patterns in cutaneous melanoma liver metastases: frequency, characteristics, and robust prognostic value.
Raymond Barnhill, Pieter-Jan van Dam, +12 authors, Claire Lugassy.
J Pathol Clin Res, 2020 Apr 19; 6(3). PMID: 32304183    Free PMC article.
M Luisa Iruela-Arispe, Greg J Beitel.
Development, 2013 Jul 04; 140(14). PMID: 23821032    Free PMC article.
Profile of treatment-related complications in women with clinical stage IB-IIB cervical cancer: A nationwide cohort study in Japan.
Hiroko Machida, Koji Matsuo, +3 authors, Mikio Mikami.
PLoS One, 2019 Jan 08; 14(1). PMID: 30615679    Free PMC article.
Modulation the crosstalk between tumor-associated macrophages and non-small cell lung cancer to inhibit tumor migration and invasion by ginsenoside Rh2.
Honglin Li, Nan Huang, +8 authors, Yan Li.
BMC Cancer, 2018 May 23; 18(1). PMID: 29783929    Free PMC article.
Angiogenesis: Managing the Culprits behind Tumorigenesis and Metastasis.
Ashwaq Hamid Salem Yehya, Muhammad Asif, +4 authors, Chern Ein Oon.
Medicina (Kaunas), 2018 Oct 23; 54(1). PMID: 30344239    Free PMC article.
Histopathological growth pattern, proteolysis and angiogenesis in chemonaive patients resected for multiple colorectal liver metastases.
Rikke Løvendahl Eefsen, Gert G Van den Eynden, +10 authors, Martin Illemann.
J Oncol, 2012 Aug 25; 2012. PMID: 22919385    Free PMC article.
Aberrant IDH3α expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis.
L Zeng, A Morinibu, +13 authors, H Harada.
Oncogene, 2014 Dec 23; 34(36). PMID: 25531325
Hypoxia, tumour-associated macrophages, microvessel density, VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival.
Sergej Osinsky, Larissa Bubnovskaya, +4 authors, Sergej Merentsev.
Clin Transl Oncol, 2011 Feb 18; 13(2). PMID: 21324802
Epithelial-to-endothelial transition and cancer stem cells: two cornerstones of vasculogenic mimicry in malignant tumors.
Baocun Sun, Danfang Zhang, Nan Zhao, Xiulan Zhao.
Oncotarget, 2016 Apr 02; 8(18). PMID: 27034014    Free PMC article.
Highly Cited. Review.
Association between vascular endothelial growth factor expression and lymph node metastasis in cervical cancer: A meta-analysis.
Haiying Sun, Fangxu Tang, +7 authors, Shuang Li.
J Obstet Gynaecol Res, 2016 Jun 24; 42(10). PMID: 27334572
Normalization of Tumor Vessels by Tie2 Activation and Ang2 Inhibition Enhances Drug Delivery and Produces a Favorable Tumor Microenvironment.
Jin-Sung Park, Il-Kug Kim, +12 authors, Gou Young Koh.
Cancer Cell, 2016 Dec 14; 30(6). PMID: 27960088
Highly Cited.
The "cavitary" type of angiogenesis by gastric cancer. Morphological characteristics and prognostic value.
Marina Senchukova, Mikhail V Kiselevsky.
J Cancer, 2014 Apr 12; 5(5). PMID: 24723973    Free PMC article.
Analysis of late adverse events and their chronological changes after radiation therapy for cervical cancer.
Takehiro Yamada, Shunichi Ishihara, +3 authors, Mitsuru Ikeda.
Nagoya J Med Sci, 2018 Dec 28; 80(4). PMID: 30587863    Free PMC article.
Cellular and Molecular Heterogeneity Associated with Vessel Formation Processes.
Pollyana Ribeiro Castro, Alan Sales Barbosa, +6 authors, Luciola Silva Barcelos.
Biomed Res Int, 2018 Nov 09; 2018. PMID: 30406137    Free PMC article.