Does the Expression of Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Have a Prognostic Significance in Advanced Non-Small Cell Lung Cancer?

doi:10.3390/healthcare11030292

. 2023 Jan 18;11(3):292.

doi: 10.3390/healthcare11030292.

Does the Expression of Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Have a Prognostic Significance in Advanced Non-Small Cell Lung Cancer?

Marina Markovic^{1

2}, Slobodanka Mitrovic^{3

4}, Aleksandar Dagovic^{2

5}, Dalibor Jovanovic³, Tomislav Nikolic^{1

6}, Anita Ivosevic^{1

7}, Milos Z Milosavljevic⁴, Radisa Vojinovic^{8

9}, Marina Petrovic^{1

10}

Affiliations

¹ Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
² Department of Medical Oncology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.
³ Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
⁴ Department of Pathology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.
⁵ Department of Oncology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
⁶ Clinic for Nephrology and Dyalisis, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.
⁷ Clinic for Rheumatology and Allergology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.
⁸ Department of Radiology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.
⁹ Department of Radiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
¹⁰ Pulmonology Clinic, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.

PMID: 36766867
PMCID: PMC9914895
DOI: 10.3390/healthcare11030292

Does the Expression of Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Have a Prognostic Significance in Advanced Non-Small Cell Lung Cancer?

Marina Markovic et al. Healthcare (Basel). 2023.

. 2023 Jan 18;11(3):292.

doi: 10.3390/healthcare11030292.

Authors

Affiliations

¹ Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
² Department of Medical Oncology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.
³ Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
⁴ Department of Pathology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.
⁵ Department of Oncology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
⁶ Clinic for Nephrology and Dyalisis, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.
⁷ Clinic for Rheumatology and Allergology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.
⁸ Department of Radiology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.
⁹ Department of Radiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
¹⁰ Pulmonology Clinic, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia.

PMID: 36766867
PMCID: PMC9914895
DOI: 10.3390/healthcare11030292

Abstract

Lung cancer is the most common cause of mortality from malignant tumors worldwide. The five-year survival rate for people with advanced stages varies considerably, from 35.4% to 6.9%. The angiogenic potential of bcl2 is not well known, nor is the way in which tumor cells with excessive bcl2 expression affect VEGF production. Hypothetically, given that tumor growth, progression and metastasis are dependent on angiogenesis, the antiapoptotic effect is expected to form a link between these two molecules. The aim of this study was to evaluate the relationship between bcl-2 and VEGF expression, clinicopathological features and survival in 216 patients with advanced NSCLC. Archival tumor tissues were examined by immunohistochemistry for the expression of bcl-2 and VEGF. Immunoreactivity for bcl-2 was observed in 41.4% of NSCLCs, 51% of squamous and 34.8% of adenocarcinomas-expressed Bcl-2. There was an inverse correlation of mononuclear stromal reaction and bcl-2 expression in adenocarcinoma (p < 0.0005). A total of 71.8% NSCLCs were VEGF positive, 56% of squamous and 82.2% of adenocarcinomas. High level of VEGF expression was significantly associated with histology type (p = 0.043), low histology grade (p = 0.014), clinical stage IV (p = 0.018), smoking history (p = 0.008) and EGFR mutations (p = 0.026). There was an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC patients (p = 0.039, r = -0.163). Two-year survival of patients with unresectable NSCLC was 39.3%, and 50% of patients were alive at 17 months. Our results demonstrated no difference in survival for patients in advanced NSCLC grouped by bcl-2 and VEGF status. Additionally, we observed an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC and mononuclear reaction and bcl-2 expression in adenocarcinomas.

Keywords: VEGF; adenocarcinoma (ACs); bcl-2; non-small cell lung carcinoma (NSCLC); squamous cell carcinoma (SCCs).

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Association of Bcl-2 expression with histological grade and mononuclear stromal reaction; (A) influence of histological grade on bcl-2 expression; histomorphological presentation of positive correlation of bcl-2 expression and histological grade (C); inverse correlation of mononuclear stromal reaction and bcl-2 expression in adenocarcinoma (B); histomorphological representation of the intensity of mononuclear stromal reaction and bcl-2 expression in adenocarcinoma (D).

**Figure 2**
Assotiation between the IHC expression of VEGF and clinicopathiological features (A) histological type; (B) histological grade; (C) stage disease; (D) smoking status.

**Figure 3**
Graphic and histomorphological presentation of inverse Correlation between Bcl-2 and VEGF expression in NSCLC. (A) graphic of inverse corelation; (B,C) histomorphological presentation.

**Figure 4**
Association of the proliferation index with the expression of VEGFa and Bcl-2. (A) graphic and histomorphological presentation of positive correlation between VEGF and the Ki-67 proliferation index in NSCLC patients; (B) relationship between Ki-67 proliferative index and bcl-2 expression in NSCLC patients (C) graphic and histomorphological presentation of inverse correlation between Bcl-2 and the Ki-67 proliferation index in adenocarcinomas.

**Figure 5**
Kaplan-Meier overall survival analysis of patients with non-small lung cell carcinoma. (A) histology type; (B) expression status of VEGF; (C) expression status of Ki67; (D) expression status of Bcl-2.

See this image and copyright information in PMC

Cited by

Paracrine Regulation and Immune System Pathways in the Inflammatory Tumor Microenvironment of Lung Cancer: Insights into Oncogenesis and Immunotherapeutic Strategies.
Batrash F, Shaik A, Rauf R, Kutmah M, Zhang J. Batrash F, et al. Cancers (Basel). 2024 Mar 10;16(6):1113. doi: 10.3390/cancers16061113. Cancers (Basel). 2024. PMID: 38539448 Free PMC article. Review.

References

1. Howlader N.N.A., Krapcho M., Miller D., Brest A., Yu M., Ruhl J., Tatalovich Z., Mariotto A., Lewis D.R., Chen H.S., et al., editors. SEER Cancer Statistics Review, 1975–2017. National Cancer Institute; Bethesda, MD, USA: 2020. [(accessed on 1 April 2020)]. Available online: https://seer.cancer.gov/csr/1975_2017/
1. Gurguş D., Grigoraş M.L., Motoc A.G.M., Zamfir C.L., Cornianu M., Faur C.I., Pop D.L., Folescu R. Clinical relevance and accuracy of p63 and TTF-1 for better approach of small cell lung carcinoma versus poorly differentiated nonkeratinizing squamous cell carcinoma. Rom. J. Morphol Embryol. 2019;60:139–143. - PubMed
1. Moldvay J., Jackel M., Bogos K., Soltész I., Agócs L., Kovács G., Schaff Z. The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas. Pathol. Oncol. Res. 2004;10:85–88. doi: 10.1007/BF02893461. - DOI - PubMed
1. Ma Y., Fan M., Dai L., Kang X., Liu Y., Sun Y., Xiong H., Liang Z., Yan W., Chen K. Expression of p63 and CK5/6 in early-stage lung squamous cell carcinoma is not only an early diagnostic indicator but also correlates with a good prognosis. Thorac. Cancer. 2015;6:288–295. doi: 10.1111/1759-7714.12181. - DOI - PMC - PubMed
1. Kim J.H., Kim H.S., Kim B.J., Han B., Choi D.R., Kwon J.H. Prognostic Impact of TTF-1 Expression in Non-Squamous Non-Small-Cell Lung Cancer: A Meta-Analysis. J. Cancer. 2018;9:4279–4286. doi: 10.7150/jca.26830. - DOI - PMC - PubMed

Grants and funding

This research received no external funding.

LinkOut - more resources

Full Text Sources
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

[1] Howlader N.N.A., Krapcho M., Miller D., Brest A., Yu M., Ruhl J., Tatalovich Z., Mariotto A., Lewis D.R., Chen H.S., et al., editors. SEER Cancer Statistics Review, 1975–2017. National Cancer Institute; Bethesda, MD, USA: 2020. [(accessed on 1 April 2020)]. Available online: https://seer.cancer.gov/csr/1975_2017/

[2] Howlader N.N.A., Krapcho M., Miller D., Brest A., Yu M., Ruhl J., Tatalovich Z., Mariotto A., Lewis D.R., Chen H.S., et al., editors. SEER Cancer Statistics Review, 1975–2017. National Cancer Institute; Bethesda, MD, USA: 2020. [(accessed on 1 April 2020)]. Available online: https://seer.cancer.gov/csr/1975_2017/

[3] Gurguş D., Grigoraş M.L., Motoc A.G.M., Zamfir C.L., Cornianu M., Faur C.I., Pop D.L., Folescu R. Clinical relevance and accuracy of p63 and TTF-1 for better approach of small cell lung carcinoma versus poorly differentiated nonkeratinizing squamous cell carcinoma. Rom. J. Morphol Embryol. 2019;60:139–143. - PubMed

[4] Gurguş D., Grigoraş M.L., Motoc A.G.M., Zamfir C.L., Cornianu M., Faur C.I., Pop D.L., Folescu R. Clinical relevance and accuracy of p63 and TTF-1 for better approach of small cell lung carcinoma versus poorly differentiated nonkeratinizing squamous cell carcinoma. Rom. J. Morphol Embryol. 2019;60:139–143. - PubMed

[5] Moldvay J., Jackel M., Bogos K., Soltész I., Agócs L., Kovács G., Schaff Z. The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas. Pathol. Oncol. Res. 2004;10:85–88. doi: 10.1007/BF02893461. - DOI - PubMed

[6] Moldvay J., Jackel M., Bogos K., Soltész I., Agócs L., Kovács G., Schaff Z. The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas. Pathol. Oncol. Res. 2004;10:85–88. doi: 10.1007/BF02893461. - DOI - PubMed

[7] Ma Y., Fan M., Dai L., Kang X., Liu Y., Sun Y., Xiong H., Liang Z., Yan W., Chen K. Expression of p63 and CK5/6 in early-stage lung squamous cell carcinoma is not only an early diagnostic indicator but also correlates with a good prognosis. Thorac. Cancer. 2015;6:288–295. doi: 10.1111/1759-7714.12181. - DOI - PMC - PubMed

[8] Ma Y., Fan M., Dai L., Kang X., Liu Y., Sun Y., Xiong H., Liang Z., Yan W., Chen K. Expression of p63 and CK5/6 in early-stage lung squamous cell carcinoma is not only an early diagnostic indicator but also correlates with a good prognosis. Thorac. Cancer. 2015;6:288–295. doi: 10.1111/1759-7714.12181. - DOI - PMC - PubMed

[9] Kim J.H., Kim H.S., Kim B.J., Han B., Choi D.R., Kwon J.H. Prognostic Impact of TTF-1 Expression in Non-Squamous Non-Small-Cell Lung Cancer: A Meta-Analysis. J. Cancer. 2018;9:4279–4286. doi: 10.7150/jca.26830. - DOI - PMC - PubMed

[10] Kim J.H., Kim H.S., Kim B.J., Han B., Choi D.R., Kwon J.H. Prognostic Impact of TTF-1 Expression in Non-Squamous Non-Small-Cell Lung Cancer: A Meta-Analysis. J. Cancer. 2018;9:4279–4286. doi: 10.7150/jca.26830. - DOI - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Does the Expression of Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Have a Prognostic Significance in Advanced Non-Small Cell Lung Cancer?

Affiliations

Does the Expression of Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Have a Prognostic Significance in Advanced Non-Small Cell Lung Cancer?

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous