Correlation of endothelial cell proliferation with vascular endothelial growth factor in endometrium of women with menorrhagia

Authors

  • Kiran B. Mehra Department of Pathology, MGIMS Sevagram, Wardha, Maharastra, India
  • Nitin M. Gangane Department of Pathology, MGIMS Sevagram, Wardha, Maharastra, India
  • Deepti R. Joshi Department of Pathology, AIIMS, Bhopal, Madhya Pradesh, India

DOI:

https://doi.org/10.18203/2320-6012.ijrms20171838

Keywords:

Angiogenesis, Endometrium, Endothelial cells, Menorrhagia, VEGF

Abstract

Background: Approximately 30% of women of reproductive age experience excessive blood loss during menstruation. In 50% of cases, menorrhagia has no underlying pathology. However, until recently, the only permanent cure for menorrhagia was hysterectomy. In this study we aim to determine the correlation of vascular endothelial growth factor (VEGF) expression with markers of endometrial endothelial cell proliferation like proliferating cell nuclear antigen (PCNA) and Cluster Determination (CD34).

Methods: A total of 100 patients with history of menorrhagia were selected for study. Double Immunohistochemistry was performed on these endometrial biopsy sections. Proliferating endothelial cells were identified by an immunohistochemical double staining technique with PCNA and CD34. VEGF expression was also seen in endometrial biopsy.

Results: In general, expression of both VEGF and PCNA was more in functional layer than basal layer in both menorrhagic patients as well as non menorrhagic patients.  When glandular cytoplasmic VEGF expression was compared with PCNA the association was statistically significant whereas completely opposite findings was seen with glandular luminal surface VEGF positivity but the association was statistically significant. In secretory phase (p-value<0.001) there was highly statistically significant association in PCNA grading with glandular luminal surface VEGF positivity whereas when we correlated PCNA with  cytoplasmic  glandular VEGF in secretory phase it was statistically significant (p-value<0.001).

Conclusions: The endothelial proliferation was significantly higher in menorrhagia patients during late secretory phase of cycle than controls. We were able to demonstrate increased endothelial proliferation in patients in the premenstrual part of cycle.

Author Biographies

Nitin M. Gangane, Department of Pathology, MGIMS Sevagram, Wardha, Maharastra, India

Department of Pathology,

Professor and Head

MGIMS Sevagram

Deepti R. Joshi, Department of Pathology, AIIMS, Bhopal, Madhya Pradesh, India

Department of Pathology

Associate Professor

AIIMS Bhopal

References

Rybo G. Clinical and experimental studies on menstrual blood loss. Acta Obstet Gynecol Scand 1966;45:Suppl 7:1-23.

Malik S, Day K, Perrault I, Charnock-Jones DS, Smith SK. Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-alpha in menstrual endometrium and effluent in women with menorrhagia. Hum Reprod 2006;2198:2158-66.

Smith SK. Angiogenesis, vascular endothelial growth factor and the endometrium. Hum Reprod Update.1998;(5):509-19.

Girling JE, Rogers PA. Recent advances in endometrial angiogenesis research. Angiogenesis. 2005;(2):89-99.

Rogers PA, Lederman F, Taylor N. Endometrial microvascular growth in normal and dysfunctional states. Human reproduction update. 1998;(5):503-8.

Rogers PAW, Abberton Km, Susil B. Endothelial cell migratory signal produced by human endometrium dyring the menstrual cycle. Hum Reprod 1992;7:1061-6.

Mints M, Blomgren B, Falconer C, Palmblad J. Expression of the vascular endothelial growth factor (VEGF) family in human endometrial blood vessels. Scand J Clin Lab Invest. 2002;62(3):167-75.

Shifren JL, Tseng JF, Zaloudek CJ, Ryan IP, Meng YG, Ferrara N, et al. Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis. J Clin Endocrinol Metab. 1996;81 (8):3112-8.

Culling CFA, Allison RT, Barr WT. Cellular Pathology Technique. 4th ed. London: Butterworth & Co. (Publishers) Ltd; 1985.

Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril. 1950;1:3-25

Christensen NK, Winther L. Multi-staining immunohistochemistry. In Kumar GL, Rudbeck L‘s Immunohistochemical staining methods. 5th ed. California; Dako North America; 2009:103-8.

Vander Loos C. User Protocol: Practical guide to multiple staining (internet). Netherland: unknown: publisher: cited 2015 March 7. Available from www.biotechniques.com.

Gargett CE, Lederman FL, Lau TM, Taylor NH, Rogers PA. Lack of correlation between vascular endothelial growth factor production and endothelial cell proliferation in the human endometrium. Hum Reprod. 1999;(8):2080-8.

Taylor CR, Shi SR, Barr NJ, Wu N. Techniques of immunohistochemistry: principles, pitfalls, and standardization. Diagnostic immunohistochemistry. 2002;2:3-44.

Elias JM. Immunohistopathology: A practical approach to diagnosis. American Society of Clinical Pathology. Chicago;1990.

Shi SR, Key ME, Kalra KL. Antigen Retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J. Histochem Cytochem. 1991;39:741-8.

Shi SR, Gu J, Kalra KL, Chen T, Cote RJ and Taylor CR. Antigen Retrieval tecniques: a novel approach to immunohistochemistry on routinely processed tissue sections. Cell Vision. 1995;2:6-22.

Nadji M, Morales AR. Immunoperoxidase, part I: the techniques and it’s pitfalls. Lab Med 1983;14:767-70.

Kooy J, Taylor NH, Healy DL, Rogers PA. Endothelial cell proliferation in the endometrium of women with menorrhagia and in women following endometrial ablation, Hum Reprod. 1996;(5):1067-72.

Goodger AM, Rogers PA. Endometrial endothelial cell proliferation during the menstrual cycle. Hum Reprod. 1994;(3):399-405.

Subakir SB, Abberton KM, Rogers PAW. Endometrial angiogenic response in patients with menorrhagia. Med J Univ Indonesia. 1992;1:71-3.

Wingfield M, Macpherson A, Healy DL, Rogers PA. Cell proliferation is increased in the endometrium of women with endometriosis. Fertil Steril. 1995;64(2):340-6.

Gargett CE, Lederman F, Heryanto B, Gambino LS, Rogers PA. Focal vascular endothelial growth factor correlates with angiogenesis in human endometrium. Role of intravascular neutrophils. Hum Reprod. 2001;(6):1065-75.

Mints M, Blomgren B, Falconer C, Fianu-Jonasson A, Palmblad J. Microvascular density, vascular endothelial growth factor A, and its receptors in endometrial blood vessels in patients with menorrhagia. Fertil Steril. 2005;84(3):692-700.

Mints M, Hultenby K, Zetterberg E, Blomgren B, Falconer C, Rogers R, Palmblad J. Wall discontinuities and increased expression of vascular endothelial growth factor-A and vascular endothelial growth factor receptors 1 and 2 in endometrial blood vessels of women with menorrhagia. Fertility and sterility. 2007;88(3):691-7.

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Published

2017-04-26

How to Cite

Mehra, K. B., Gangane, N. M., & Joshi, D. R. (2017). Correlation of endothelial cell proliferation with vascular endothelial growth factor in endometrium of women with menorrhagia. International Journal of Research in Medical Sciences, 5(5), 2034–2039. https://doi.org/10.18203/2320-6012.ijrms20171838

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Section

Original Research Articles