Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field

Yasuhito Hagiwara; Kenji Nemoto; Ibuki Ota; Masayoshi Yamada; Osamu Hachiya; Mitsunori Yamakawa

doi:doi:10.11648/j.ijcocr.20210601.12

| Peer-Reviewed

Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field

Yasuhito Hagiwara, Kenji Nemoto, Ibuki Ota, Masayoshi Yamada, Osamu Hachiya, Mitsunori Yamakawa

Published in International Journal of Clinical Oncology and Cancer Research (Volume 6, Issue 1)

Received: 29 December 2020 Accepted: 8 January 2021 Published: 22 January 2021

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

Background and objective: If it becomes possible to reduce the prophylactic radiation field by using a personalized radiation field, radiation therapy of esophageal cancer may become safer. In this study, we examined the relationship between expression levels of biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) and lymph node metastasis and distant metastasis. Materials and methods: We performed retrospective analysis of 14 patients who underwent radical surgery for esophageal cancer between 2009 and 2011 in Yamagata University Hospital. Stain index was used for assessment of biomarker expression. The relationships of stain index with regional recurrence and distant metastasis were evaluated. Results: All patients had squamous cell carcinoma. The median follow-up duration was 38 months. Distant failure was significantly related to low COX-2 expression in the deep part of the tumor (stain index <2.8; p=0.0479). Pathological node-positive or regional recurrence was significantly related to low VEGF-C expression (stain index <0.3; p=0.0418). Patients with low CD44 expression in the surface of the tumor tended to have better reginal control (stain index <0.3; p=0.0902). Conclusions: COX-2, VEGF-C, and CD44 expression levels might have potential to enable omission of the prophylactic radiation field. Further analysis using biopsy samples is required for application to radical radiotherapy.

Published in	International Journal of Clinical Oncology and Cancer Research (Volume 6, Issue 1)
DOI	10.11648/j.ijcocr.20210601.12
Page(s)	10-16
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Esophageal Cancer, CD44 Antigen, Cyclooxygenase 2, Vascular Endothelial Growth Factor C, Lymphatic Metastasis

References

[1]	Herskovic A, LeichmanL, Lattin P, Han I, Ahmad K, Leichman G, et al. Chemo/radiation with and without surgery in the thoracic esophagus: the Wayne State experience. Int J Radiat Oncol Biol Phys. 1988; 15 (3): 655-662 [Pubmed: 3138217] [doi: 10.1016/0360-3016(88)90308-2].
[2]	Konski A, Doss M, Milestone B, Haluszka O, Hanlon A, Freedman G, et al. The integration of 18-fluoro-deoxy-glucose positron emission tomography and endoscopic ultrasound in the treatment-planning process for esophageal carcinoma. Int J Radiat Oncol Biol Phys. 2005; 61 (4): 1123-1128 [Pubmed: 15752892] [doi: 10.1016/j.ijrobp.2004.07.717].
[3]	Toya R, Matsuyama T, Saito T, Imuta M, Shiraishi S, Fukugawa Y, et al. Impact of hybrid FDG-PET/CT on gross tumor volume definition of cervical esophageal cancer: reducing interobserver variation. J Radiat Res. 2019; 60 (3): 348-352 [Pubmed: 30864652] [doi: 10.1093/jrr/rrz004].
[4]	Schröder W, Baldus SE, Mönig SP, Beckurts TK, Dienes HP, Hölscher AH. Lymph node staging of esophageal squamous cell carcinoma in patients with and without neoadjuvant radiochemotherapy: histomorphologic analysis. World J Surg. 2002; 26 (5): 584-587 [Pubmed: 12098049] [doi: 10.1007/s00268-001-0271-5].
[5]	Chang EY, Li X, Jerosch-Herold M, Priest RA, Enestvedt CK, Xu J, et al. The evaluation of esophageal adenocarcinoma using dynamic contrast-enhanced magnetic resonance imaging. J Gastrointest Surg. 2008; 12 (1): 166-175 [Pubmed: 17768665] [doi: 10.1007/s11605-007-0253-5].
[6]	Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002; 20 (5): 1167-1174 [Pubmed: 11870157] [doi: 10.1200/JCO.2002.20.5.1167].
[7]	Kato K, Muro K, Minashi K, Ohtsu A, Ishikura S, Boku N, et al. Phase II study of chemoradiotherapy with 5-fluorouracil and cisplatin for stage II-III esophageal squamous cell carcinoma: JCOG trial (JCOG 9906). Int J Radiat Oncol Biol Phys. 2011; 81 (3): 684-690 [Pubmed: 20932658] [doi: 10.1016/j.ijrobp.2010.06.033].
[8]	Kato H, Sato A, Fukuda H, Kagami Y, Udagawa H, Togo A, et al. A phase II trial of chemoradiotherapy for stage I esophageal squamous cell carcinoma: Japan Clinical Oncology Group Study (JCOG 9708). Jpn J Clin Oncol. 2009; 39 (10): 638-643 [Pubmed: 19549720] [doi: 10.1093/jjco/hyp069].
[9]	Collard JM, Otte JB, Fiasse R, Laterre PF, De Kock M, Longueville J, et al. Skeletonizing en bloc esophagectomy for cancer. Ann Surg. 2001; 234 (1): 25-32 [Pubmed: 11420480] [doi: 10.1097/00000658-200107000-00005].
[10]	Dresner SM, Lamb PJ, Bennett MK, Hayes N, Griffin SM. The pattern of metastatic lymph node dissemination from adenocarcinoma of the esophagogastric junction. Surgery. 2001; 129 (1): 103-109 [Pubmed: 11150040] [doi: 10.1067/msy.2001.110024].
[11]	Akiyama H, Tsurumaru M, Kawamura T, Ono Y. Principles of surgical treatment for carcinoma of the esophagus: analysis of lymph node involvement. Ann Surg. 1981; 194 (4): 438-446 [Pubmed: 7283505] [doi: 10.1097/00000658-198110000-00007].
[12]	Huang W, Li B, Gong H, Yu J, Sun H, Zhou T, et al. Pattern of lymph node metastases and its implication in radiotherapeutic clinical target volume in patients with thoracic esophageal squamous cell carcinoma: a report of 1077 cases. Radiother Oncol. 2010; 95 (2): 229-233 [Pubmed: 20189259] [doi: 10.1016/j.radonc.2010.01.006].
[13]	Ishikura S, Nihei K, Ohtsu A, Boku N, Hironaka S, Mera K, et al. Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol. 2003; 21 (14): 2697-2702 [Pubmed: 12860946] [doi: 10.1200/JCO.2003.03.055].
[14]	Morota M, Gomi K, Kozuka T, Chin K, Matsuura M, Oguchi M, et al. Late toxicity after definitive concurrent chemoradiotherapy for thoracic esophageal carcinoma. Int J Radiat Oncol Biol Phys. 2009; 75 (1): 122-128 [Pubmed: 19327900] [doi: 10.1016/j.ijrobp.2008.10.075].
[15]	Gotoda T, Matsumura Y, Kondo H, Ono H, Kanamoto A, Kato H, et al. Expression of CD44 variants and prognosis in oesophageal squamous cell carcinoma. Gut. 2000; 46 (1): 14-19 [Pubmed: 10601048] [doi: 10.1136/gut.46.1.14].
[16]	Huang JX, Chen WC, Lin M, Zhang YL, Li FY, Song ZX, et al. Clinicophathological significance of cyclooxygenase-2 and cell cycle-regulatory proteins expression in patients with esophageal squamous cell carcinoma. Dis Esophagus. 2012; 25 (2): 121-129 [Pubmed: 21762277] [doi: 10.1111/j.1442-2050.2011.01219.x].
[17]	Byeon JS, Jung HY, Lee YJ, Lee D, Lee GH, Myung SJ, et al. Clinicophathological significance of vascular endothelial growth factor-C and cyclooxygenase-2 in esophageal squamous cell carcinoma. J Gastroenterol Hepatol. 2004; 19 (6): 648-654 [Pubmed: 15151619] [doi: 10.1111/j.1440-1746.2004.03348.x].
[18]	Han U, Can OI, Han S, Kayhan B, Onal BU. Expressions of p53, VEGF C, p21: could they be used in preoperative evaluation of lymph node metastasis of esophageal squamous cell carcinoma? Dis Esophagus. 2007; 20 (5): 379-385 [Pubmed: 17760650] [doi: 10.1111/j.1442-2050.2007.00634.x].
[19]	Kitadai Y, Amioka T, Haruma K, Tanaka S, Yoshihara M, Sumii K, et al. Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinomas. Int J Cancer. 2001; 93 (5): 662-666 [Pubmed: 11477575] [doi: 10.1002/ijc.1379].
[20]	Sakai M, Kato H, Sano A, Tanaka N, Inose T, Kimura H, et al. Expression of lysyl oxidase is correlated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma. Ann Surg Oncol. 2009; 16 (9): 2494-2501 [Pubmed: 19526206] [doi: 10.1245/s10434-009-0559-5].
[21]	Donahue JM, Nichols FC, Li Z, Schomas DA, Allen MS, Cassivi SD, et al. Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg. 2009; 87 (2): 392-398 [Pubmed: 19161745] [doi: 10.1016/j.athoracsur.2008.11.001].
[22]	Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 2012; 19 (1): 68-74 [Pubmed: 21879261] [doi: 10.1245/s10434-011-2049-9].
[23]	King RJ, Coffer AI, Gilbert J, Lewis K, Nash R, Millis R, et al. Histochemical studies with a monoclonal antibody raised against a partially purified soluble estradiol receptor preparation from human myometrium. Cancer Res. 1985; 45 (11pt2): 5728-5733 [Pubmed: 2413995].
[24]	Rizzo MT. Cyclooxygenase-2 in oncogenesis. Clin Chim Acta. 2011; 412 (9-10): 671-687 [Pubmed: 21187081] [doi: 10.1016/j.cca.2010.12.026].
[25]	Hu Z, Yang Y, Zhao Y, Huang Y. The prognostic value of cyclooxygenase-2 expression in patients with esophageal cancer: evidence from a meta-analysis. Onco Targets Ther. 2017; 10: 2893-2901 [Pubmed: 28652771] [doi: 10.2147/OTT.S134599].
[26]	Sivula A, Buskens CJ, van Rees BP, Haglund C, Offerhaus GJ, van Lanschot JJ, et al. Prognostic role of cyclooxygenase-2 in neoadjuvant-treated patients with squamous cell carcinoma of the esophagus. Int J Cancer. 2005; 116 (6): 903-908 [Pubmed: 15856454] [doi: 10.1002/ijc.21134].
[27]	Pan X, Mao T, Fang W, Chen W. Vascular endothelial growth factor C is an indicator of lymph node metastasis in thoracic esophageal squamous cell carcinomas and its role in long-term survival after surgery. Thrac Cancer. 2014; 5 (4): 313-318 [Pubmed: 26767018] [doi: 10.1111/1759-7714.12094].
[28]	Nair KS, Naidoo R, Chetty R. Expression of cell adhesion molecules in oesophageal carcinoma and its prognostic value. J Clin Pathol. 2005; 58 (4): 343-351 [Pubmed: 15790695] [doi: 10.1136/jcp.2004.018036].
[29]	Kinugasa H, Whelan KA, Tanaka K, Natsuizaka M, Long A, Guo A, et al. Mitochondrial SOD2 regulates epithelial-mesenchymal transition and cell populations defined by differential CD44 expression. Oncogene. 2015; 34 (41): 5229-5239 [Pubmed: 25659582] [doi: 10.1038/onc.2014.449].
[30]	Liu S, Anfossi S, Qiu B, Zheng Y, Cai M, Fu J, et al. Prognostic factors for locoregional recurrence in patients with thoracic esophageal squamous cell carcinoma treated with radical two-field lymph node dissection: results from long-term follow-up. Ann Surg Oncol. 2017; 24 (4): 966-973 [Pubmed: 27804027] [doi: 10.1245/s10434-016-5652-y].

Cite This Article

Plain Text BibTeX RIS

APA Style

Yasuhito Hagiwara, Kenji Nemoto, Ibuki Ota, Masayoshi Yamada, Osamu Hachiya, et al. (2021). Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field. International Journal of Clinical Oncology and Cancer Research, 6(1), 10-16. https://doi.org/10.11648/j.ijcocr.20210601.12

Copy | Download

ACS Style

Yasuhito Hagiwara; Kenji Nemoto; Ibuki Ota; Masayoshi Yamada; Osamu Hachiya, et al. Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field. Int. J. Clin. Oncol. Cancer Res. 2021, 6(1), 10-16. doi: 10.11648/j.ijcocr.20210601.12

Copy | Download

AMA Style

Yasuhito Hagiwara, Kenji Nemoto, Ibuki Ota, Masayoshi Yamada, Osamu Hachiya, et al. Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field. Int J Clin Oncol Cancer Res. 2021;6(1):10-16. doi: 10.11648/j.ijcocr.20210601.12

Copy | Download

@article{10.11648/j.ijcocr.20210601.12,
  author = {Yasuhito Hagiwara and Kenji Nemoto and Ibuki Ota and Masayoshi Yamada and Osamu Hachiya and Mitsunori Yamakawa},
  title = {Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field},
  journal = {International Journal of Clinical Oncology and Cancer Research},
  volume = {6},
  number = {1},
  pages = {10-16},
  doi = {10.11648/j.ijcocr.20210601.12},
  url = {https://doi.org/10.11648/j.ijcocr.20210601.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcocr.20210601.12},
  abstract = {Background and objective: If it becomes possible to reduce the prophylactic radiation field by using a personalized radiation field, radiation therapy of esophageal cancer may become safer. In this study, we examined the relationship between expression levels of biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) and lymph node metastasis and distant metastasis. Materials and methods: We performed retrospective analysis of 14 patients who underwent radical surgery for esophageal cancer between 2009 and 2011 in Yamagata University Hospital. Stain index was used for assessment of biomarker expression. The relationships of stain index with regional recurrence and distant metastasis were evaluated. Results: All patients had squamous cell carcinoma. The median follow-up duration was 38 months. Distant failure was significantly related to low COX-2 expression in the deep part of the tumor (stain index Conclusions: COX-2, VEGF-C, and CD44 expression levels might have potential to enable omission of the prophylactic radiation field. Further analysis using biopsy samples is required for application to radical radiotherapy.},
 year = {2021}
}

Copy | Download

TY  - JOUR
T1  - Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field
AU  - Yasuhito Hagiwara
AU  - Kenji Nemoto
AU  - Ibuki Ota
AU  - Masayoshi Yamada
AU  - Osamu Hachiya
AU  - Mitsunori Yamakawa
Y1  - 2021/01/22
PY  - 2021
N1  - https://doi.org/10.11648/j.ijcocr.20210601.12
DO  - 10.11648/j.ijcocr.20210601.12
T2  - International Journal of Clinical Oncology and Cancer Research
JF  - International Journal of Clinical Oncology and Cancer Research
JO  - International Journal of Clinical Oncology and Cancer Research
SP  - 10
EP  - 16
PB  - Science Publishing Group
SN  - 2578-9511
UR  - https://doi.org/10.11648/j.ijcocr.20210601.12
AB  - Background and objective: If it becomes possible to reduce the prophylactic radiation field by using a personalized radiation field, radiation therapy of esophageal cancer may become safer. In this study, we examined the relationship between expression levels of biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) and lymph node metastasis and distant metastasis. Materials and methods: We performed retrospective analysis of 14 patients who underwent radical surgery for esophageal cancer between 2009 and 2011 in Yamagata University Hospital. Stain index was used for assessment of biomarker expression. The relationships of stain index with regional recurrence and distant metastasis were evaluated. Results: All patients had squamous cell carcinoma. The median follow-up duration was 38 months. Distant failure was significantly related to low COX-2 expression in the deep part of the tumor (stain index Conclusions: COX-2, VEGF-C, and CD44 expression levels might have potential to enable omission of the prophylactic radiation field. Further analysis using biopsy samples is required for application to radical radiotherapy.
VL  - 6
IS  - 1
ER  -

Copy | Download

Author Information

Yasuhito Hagiwara

Department of Radiation Oncology, Yamagata University Faculty of Medicine, Yamagata, Japan
Kenji Nemoto

Department of Radiation Oncology, Yamagata University Faculty of Medicine, Yamagata, Japan
Ibuki Ota

Department of Radiation Therapy, Iwate Prefectural Central Hospital, Iwate, Japan
Masayoshi Yamada

Department of Radiation Oncology, Yamagata University Faculty of Medicine, Yamagata, Japan
Osamu Hachiya

Department of Gastroenterological, General, Breast ant Thyroid Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan
Mitsunori Yamakawa

Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Japan

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Yasuhito Hagiwara, Kenji Nemoto, Ibuki Ota, Masayoshi Yamada, Osamu Hachiya, et al. (2021). Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field. International Journal of Clinical Oncology and Cancer Research, 6(1), 10-16. https://doi.org/10.11648/j.ijcocr.20210601.12

Copy | Download

ACS Style

Yasuhito Hagiwara; Kenji Nemoto; Ibuki Ota; Masayoshi Yamada; Osamu Hachiya, et al. Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field. Int. J. Clin. Oncol. Cancer Res. 2021, 6(1), 10-16. doi: 10.11648/j.ijcocr.20210601.12

Copy | Download

AMA Style

Yasuhito Hagiwara, Kenji Nemoto, Ibuki Ota, Masayoshi Yamada, Osamu Hachiya, et al. Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field. Int J Clin Oncol Cancer Res. 2021;6(1):10-16. doi: 10.11648/j.ijcocr.20210601.12

Copy | Download

@article{10.11648/j.ijcocr.20210601.12,
  author = {Yasuhito Hagiwara and Kenji Nemoto and Ibuki Ota and Masayoshi Yamada and Osamu Hachiya and Mitsunori Yamakawa},
  title = {Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field},
  journal = {International Journal of Clinical Oncology and Cancer Research},
  volume = {6},
  number = {1},
  pages = {10-16},
  doi = {10.11648/j.ijcocr.20210601.12},
  url = {https://doi.org/10.11648/j.ijcocr.20210601.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcocr.20210601.12},
  abstract = {Background and objective: If it becomes possible to reduce the prophylactic radiation field by using a personalized radiation field, radiation therapy of esophageal cancer may become safer. In this study, we examined the relationship between expression levels of biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) and lymph node metastasis and distant metastasis. Materials and methods: We performed retrospective analysis of 14 patients who underwent radical surgery for esophageal cancer between 2009 and 2011 in Yamagata University Hospital. Stain index was used for assessment of biomarker expression. The relationships of stain index with regional recurrence and distant metastasis were evaluated. Results: All patients had squamous cell carcinoma. The median follow-up duration was 38 months. Distant failure was significantly related to low COX-2 expression in the deep part of the tumor (stain index Conclusions: COX-2, VEGF-C, and CD44 expression levels might have potential to enable omission of the prophylactic radiation field. Further analysis using biopsy samples is required for application to radical radiotherapy.},
 year = {2021}
}

Copy | Download

TY  - JOUR
T1  - Expression of Biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) in Esophageal Cancer: Implication for Prophylactic Radiation Field
AU  - Yasuhito Hagiwara
AU  - Kenji Nemoto
AU  - Ibuki Ota
AU  - Masayoshi Yamada
AU  - Osamu Hachiya
AU  - Mitsunori Yamakawa
Y1  - 2021/01/22
PY  - 2021
N1  - https://doi.org/10.11648/j.ijcocr.20210601.12
DO  - 10.11648/j.ijcocr.20210601.12
T2  - International Journal of Clinical Oncology and Cancer Research
JF  - International Journal of Clinical Oncology and Cancer Research
JO  - International Journal of Clinical Oncology and Cancer Research
SP  - 10
EP  - 16
PB  - Science Publishing Group
SN  - 2578-9511
UR  - https://doi.org/10.11648/j.ijcocr.20210601.12
AB  - Background and objective: If it becomes possible to reduce the prophylactic radiation field by using a personalized radiation field, radiation therapy of esophageal cancer may become safer. In this study, we examined the relationship between expression levels of biomarkers (CD44, COX-2, TWIST, VEGF-C and LOX) and lymph node metastasis and distant metastasis. Materials and methods: We performed retrospective analysis of 14 patients who underwent radical surgery for esophageal cancer between 2009 and 2011 in Yamagata University Hospital. Stain index was used for assessment of biomarker expression. The relationships of stain index with regional recurrence and distant metastasis were evaluated. Results: All patients had squamous cell carcinoma. The median follow-up duration was 38 months. Distant failure was significantly related to low COX-2 expression in the deep part of the tumor (stain index Conclusions: COX-2, VEGF-C, and CD44 expression levels might have potential to enable omission of the prophylactic radiation field. Further analysis using biopsy samples is required for application to radical radiotherapy.
VL  - 6
IS  - 1
ER  -

Copy | Download