بیان ژن VEGF در کارسینوم پاپیلری تیروئید و ارتباط آن با عوامل موثر بر پیش‌آگهی

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه پاتولوژی و علوم تشریح، دانشکده پزشکی، دانشگاه شاهد، تهران، ایران

2 دانشکده پزشکی، دانشگاه شاهد، تهران، ایران

چکیده

مقدمه و هدف: فاکتور رشد اندوتلیال عروقی (VEGF) ارتشاح سلول‌های اندوتلیال و آنژیوژنز را تحریک می‌کند. افزایش بیان VEGF با پیامد بالینی ضعیف در بسیاری از بدخیمی‌ها مرتبط بوده است. چندین مطالعه نیز بیان افزایش یافته‌ی VEGF را در کارسینوم پاپیلری تیروئید گزارش کرده‌اند. لذا مطالعه‌ی حاضر با هدف بررسی بیان VEGF در کارسینوم پاپیلری تیروئید و ارتباط آن با عوامل موثر بر پیش‌آگهی انجام شد.
مواد و روش ها: در این مطالعه‌ی مقطعی، در مجموع 80 نمونه‌ی بلوک پارافینی کارسینوم پاپیلری تیروئید از بیماران مراجعه‌کننده به بیمارستان شهید مصطفی خمینی (ره) تهران طی سال‌های 1396 تا 1400 مورد رنگ‌آمیزی ایمونوهیستوشیمی با مارکر VEGF قرار گرفتند. شدت بیان VEGF در سلول‌های توموری به صورت خفیف (کمتر از 25%)، متوسط (50-25%) و قوی (بیشتر از 50%) درجه‌بندی شد. ارتباط درجه‌ی بیان VEGF با فاکتورهای سن، جنسیت، اندازه‌ی تومور، تهاجم به کپسول و متاستاز به غدد لنفاوی با SPSS 16 مورد تحلیل و بررسی قرار گرفت.
نتایج: میانگین سن بیماران مورد بررسی 48/14±56/40 سال و 58 بیمار (5/72%) زن بودند. بیان خفیف، متوسط و قوی VEGF به ترتیب در 3/21%، 35% و 8/43% نمونه‌ها مشاهده شد. ارتباط آماری معنی‌داری بین بیان VEGF با سن، جنسیت و اندازه‌ی تومور وجود نداشت. افزایش بیان VEGF به طور معنی‌داری با فراوانی بالاتر تهاجم به کپسول و متاستاز غدد لنفاوی مرتبط بود (P<0.001).
نتیجه‌گیری: افزایش بیان VEGF به طور شایع در کارسینوم پاپیلری تیروئید مشاهده می‌شود. بیان افزایش‌یافته‌ی VEGF یک فاکتور خطر مستقل برای تهاجم به کپسول و متاستاز به غدد لنفاوی بوده و می‌تواند به عنوان یک فاکتور پیش‌آگهی منفی و همچنین یک فاکتور بالقو‌ه‌ی درمانی در کارسینوم پاپیلری تیروئید مطرح باشد.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

VEGF gene expression in papillary thyroid carcinoma and its association with prognostic factors

نویسندگان [English]

  • Zohre Nobahar 1
  • Mohammadreza Jalali Nadoushan 2
1 Department of Pathology, School of Medicine, Shahed University, Tehran, Iran
2 Faculty of Medicine, Shahed University, Tehran, Iran
چکیده [English]

Background and Objective: Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells and angiogenesis. VEGF overexpression has been associated with poor clinical outcome in many malignancies. Also, several studies have reported increased expression of VEGF in papillary thyroid carcinoma. So, present study aimed to evaluate VEGF expression and its association with prognostic markers in papillary thyroid carcinoma.
Materials and Methods: In this cross-sectional study, totally 80 formalin fixed- paraffin embedded samples from papillary thyroid carcinoma patients referred to Shahid Mostafa Khomeini hospital, Tehran during 2017 to 2021 were immunohistochemically stained by VEGF marker. VEGF expression intensity in tumor cells scored as mild (Less than 25%), moderate (25-50%) and strong (more than 50%). Relation between VEGF expression grade with age, gender, tumor size, capsular invasion and lymph node metastasis was analyzed by SPSS software version 16.
Results: Average of patient's age was 40.56±14.48 years and 58 patients (72.5%) were female. Mild, moderate and severe expression of VEGF was seen in 21.3%, 35% and 43.8% respectively. There was no significant relationship between VEGF expression with age, gender and tumor size. Increased expression of VEGF was significantly associated with increased rate of capsular invasion and lymph node metastasis (P<0.001).
Conclusion: VEGF overexpression is frequently seen in papillary thyroid carcinoma. Increased expression of VEGF is an independent prognostic factor for capsular invasion and lymph node metastasis and could be considered as a poor prognostic and potential therapeutic factor in papillary thyroid carcinoma.

کلیدواژه‌ها [English]

  • Papillary thyroid carcinoma
  • Angiogenesis
  • Vascular endothelial growth factor
  • Prognosis

مراجع

  1. Abbas Zadeh M, Tangestani A, Jokar N, Rowan Bod M R, Hormazi Sheriff M R. Determination of prognostic factors in the survival of patients with differentiated thyroid cancer. Tebe Jounob Journal 2019; 23(3): 248-56.
  2. Jalali Nadushan M R, Sarmastzadeh T, Devati A. Comparison of BAX expression in papillary carcinoma and papillary thyroid microcarcinoma and its relationship with factors affecting prognosis. Scientific Journal of Kurdistan University of Medical Science 2016. 22(1): 9-43.
  3. Skuletic V, Radosavljevic GD, Pantic J, Markovic BS, Jovanovic I, Jankovic N, et al. Angiogenic and lymphangiogenic profiles in histological variants of papillary thyroid carcinoma. Polish Archives of Internal Medicine 2017; 127(6): 429-37.
  4. Badkobe Hazare Z, Jalali Nadushan Moh R, Azizzadeh Delshad A. CD117 expression in multinodular goiter and papillary thyroid carcinoma and its relationship with factors affecting prognosis. Journal of Mazandaran University of Medical Sciences 2019; 30 (192): 133-8.
  5. Esfandiari K, Jalali Nadushan M R, Heshmati M, Miri Seyed R. Expression of cytokeratin 7 in papillary thyroid carcinoma and its relationship with factors affecting prognosis. Daneshvar Med 1400; 29(2): 91-9.
  6. Ceric S, Ceric T, Pojskic N, Bilalovic N, Musanovic J, Kucukalic- Selimovic E. Immunohistochemical expression and prognostic significance of VEGF-C in well-differentiated thyroid cancer. Acta Endocrinologica 2020; 16(4): 409-16.
  7. Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology 2005; 69(3): 4-10.
  8. Apta RS, Chen DS, Ferrara N. VEGF in signaling and disease: Beyond discovery and development. Cell 2019; 176: 1248-64.
  9. Bunone G, Vigneri P, Mariani L, Buto S, Collini P, Pilotti S, Pierotti MA, Bongarzone I. Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features. The American Journal of Pathology 1999; 155: 1967-76.
  10. Capp C, Magagnin Wagner S, Siqueira DR, Brasil BA, Meurer L, Luiza Maia A. Increased expression of vascular endothelial growth factor and its receptors, VEGFR-1 and VEGFR-2, in Medullary Thyroid Carcinoma. Thyroid 2010; 20(8): 863071.
  11. Gonzalez R, Bologna-Molina R, Carreon-Burciaga RG, Gastelum M, Molina-Frechero N, Rodriguez SS. Papillary Thyroid Carcinoma: Differential diagnosis and prognostic values of its different variants: Review of the Literature. International Scholarly Research Notices Oncology 2011; 12: 122-8.
  12. Al-Brahim N. Papillary thyroid carcinoma: An overview. he Archives of Pathology & Laboratory Medicine 2006; 130:1057-106.
  13. Erdem H, Gundogdu Cemal C, Uipal S. Correlation of E-cadherin, VEGF, COX-2 expression to prognostic parameters in papillary thyroid carcinoma. Experimental and Molecular Pathology 2011; 90(3): 312–17.
  14. LiVolsi VA, Albores-Saavedra J, Asa SL. Papillary carcinoma. In: De Lellis, Lloyd R, Heitz PU, Eng C, eds. Pathology and Genetics of Tumors of Endocrine Organs. Lyon, France: IARC Press; 2004: 57–66.
  15. Ito Y, Kudo T, Kobayashi K, Miya A, Ichihara K, Miyauchi A. Prognostic factors for recurrence of papillary thyroid carcinoma in the lymph nodes, lung, and bone: analysis of 5,768 patients with average 10-year follow-up. World Journal of Surgery 2012; 36: 1274-8.
  16. Katoh R, Miyagi E, Kawaoi A. Expression of vascular endothelial growth factor (VEGF) in human thyroid neoplasms. Human Pathology 1999; 30: 891-7.
  17. Fellmer PT, Sato K, Tanaka R. Vascular endothelial growth factor-C gene expression in papillary and follicular thyroid carcinomas. Surgery 1999; 126: 1056-61.
  18. Razy NH, Abdul Rahman WF, Win TT. Expression of vascular endothelial growth factor and its receptors in thyroid nodular hyperplasia and papillary thyroid carcinoma: A tertiary health care center based study. The Asian Pacific Journal of Cancer Prevention 2019; 20(1): 277-82.
  19. Klein M, Picard E, Vignaud JM. Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma. Journal of Endocrinology 1999; 161: 41-9.
  20. Akagi K, IkedaY, Miyazaki M. Vascular endothelial growth factor- C (VEGF-C) expression in human colorectal cancer tissues. British Journal of Cancer 2000; 83: 887-91.
  21. KurebayashiJ, OtsukiT, Kunisue H. Expression of vascular endothelial growth factor (VEGF) family members in breast cancer. Japanese Journal of Cancer Research 1999; 90: 977-81.
  22. Shushanov S, Bronstein M, Adelaide J. VEGFc and VEGFR3 expression in human thyroid pathologies. International Journal of Cancer 2000; 86: 47-52.
  23. Hung CJ, Ginzinger DG, Zarnegar R, Kanauchi H, Wong MG, Kebebew E. Expression of vascular endothelial growth factor-C in benign and malignant thyroid tumors. Journal of Clinical Endocrinology & Metabolism 2003; 88: 3694-9.
  24. Kadivar Maryam, Esmaili Ali, Julaei Azadeh. Investigating the density of small vessels and vascular endothelial growth factor in invasive breast carcinomas by immunohistochemical marker method and comparing it with clinicopathological parameters. Iranian Journal of Medical Sciences 1388; 16(69): 55-46.
  25. Lennard CM, Patel A, Wilson J. Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery 2001; 129: 552-8.
  26. Yu XM, Lo CY, Chan WF, Lam KY, Leung P, Luk JM. Increased expression of vascular endothelial growth factor C in papillary thyroid carcinoma correlates with cervical lymph node metastases. Clinical Cancer Research 2005; 11(22): 8063-9.
  27. Jebreel A, England J, Bedford K. Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseases. International Journal of Experimental Pathology 2007; 88: 271-7.
  28. Gulubova M, Ivanova K, Ananiev J. VEGF expression, microvessel density and dendritic cell decrease in thyroid cancer. Biotechnology & Biotechnological Equipment 2014; 228: 508-17.
  29. Shaha A. Treatment of thyroid cancer based on risk groups. Journal of Surgical Oncology 2006; 94: 683-91.
  30. Ji B, Liu Y, Zhang P, et al. COX‑2 expression and tumor angiogenesis in thyroid carcinoma patients among northeast Chinese population‑result of a single‑center study. International Journal of Medicine Sciences 2012; 9: 237‑42.
  31. Ichikura T, Tomimatsu S, Ohkura E, Mochizuki H. Prognostic significance of the expression of vascular endothelial growth factor (VEGF) and VEGF-C in gastric carcinoma. Journal of Surgical Oncology 2001; 78: 132-7.
  32. Hirai M, Nakagawara A, Oosaki T, HayashiY, Hirono M, Yoshihara T. Expression of vascular endothelial growth factors (VEGF-A/VEGF-1and VEGF-C/VEGF- 2) in postmenopausal uterine endometrial carcinoma. Gynecologic Oncology 2001;80: 181-8.
  33. Kaio E, Tanaka S, Kitadai Y. Clinical significance of angiogenic factor expression at the deepest invasive site of advanced colorectal carcinoma. Oncology 2003; 64: 61-73.
  34. Salajegheh A, Pakneshan S, Rahman A. Co‑regulatory potential of vascular endothelial growth factor‑A and vascular endothelial growth factor‑C in thyroid carcinoma. Human Pathology 2013; 44: 2204‑12.
  35. Šelemetjev S, Đorić I, Paunović I, Tatić S, Cvejić D. Coexpressed high levels of VEGF-C and active MMP-9 are associated with lymphatic spreading and local invasiveness of papillary thyroid carcinoma. American Journal of Pathology 2016; 146(5): 594-602.
دانشور پزشکی
دوره 32، شماره 2 - شماره پیاپی 171
خرداد و تیر 1403
صفحه 10-20

فایل ها

هم رسانی

ارجاع به این مقاله

آمار