Lymphatic Vascularization in Primary Breast Cancer: Her2 Overexpressing Tumors Contain More Lymphatics than Steroid Receptor Positive, Triple-Positive And Triple Negative Breast Carcinomas

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Abstract

Objective: The aim of this study was to examine the relationship between the immunohistochemical subtypes of invasive breast cancer and lymphatic vascularization.

Material and Method: One hundred and seventy nine cases of randomly selected invasive breast cancer patients, surgically treated between 2004 and 2007, were retrospectively studied. These were classified into steroid receptor positive (steroid receptor positive/ HER2 negative), triple positive (steroid receptor and HER2 positive), triple negative (steroid receptor and HER2 negative) and HER2 overexpressing (steroid receptor negative /HER2 positive) carcinomas. Appropriate immunostaining and in-situ hybridization techniques were applied and results were statistically analyzed.

Results: The median intra-tumor lymphatic vascular density and the median intra-tumor relative lymphatic vascular area were found to differ significantly among the studied groups of breast cancer (KW =49.8611; p<0.0001 and KW =21.5122; p=0.0001 respectively). There was no significant difference in the incidence rate of axillary node involvement among the studied groups of breast cancer (χ2=1.66; Df=3; p=0.6460).

Conclusion: The present study indicates that HER2 overexpressing breast carcinomas have a consistent increase of intra-tumor lymphatic vessel counts as compared to all other subtypes. It is suggested that the newly formed vessels are probably not the only essential factor for lymphogenic spread of HER2 overexpressing breast carcinomas as they are not related to an increased incidence of lymph node metastases compared to the other studied subgroups.

1. Bhargava R, Beriwal S, Striebel JM, Dabbs DJ. Breast cancer molecular class ERBB2: preponderance of tumors with apocrine differentiation and expression of basal phenotype markers CK5, CK5/6, and EGFR. Appl Immunohistochem Mol Morphol. 2010;18:113-8.

2. Spitale A, Mazzola P, Soldini D, Mazzucchelli L, Bordoni A. Breast cancer classification according to immunohistochemical markers: Clinicopathologic features and short-term survival analysis in a population-based study from the south of Switzerland. Ann Oncol. 2009;20:628-35.

3. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MCU, Nielsen TO, Moorman PG, Earp HS, Millikan RC. Race, breast cancer subtypes, and survival in the carolina breast cancer study. JAMA. 2006;295:2492-502.

4. Yu Q, Niu Y, Liu N, Zhang JZ, Liu TJ, Zhang RJ, Wang SL, Ding XM, Xiao XQ. Expression of androgen receptor in breast cancer and its significance as a prognostic factor. Ann Oncol. 2011;22:1288-94.

5. Cheang MCU, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, Perou CM, Nielsen TO. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008;14:1368.

6. L aakso M, Tanner M, Nilsson J, Wiklund T, Erikstein B, Kellokumpu-Lehtinen P, Malmstrom P, Wilking N, Bergh J, Isola J. Basoluminal carcinoma: A new biologically and prognostically distinct entity between basal and luminal breast cancer. Clin Cancer Res. 2006;12:4185-91.

7. Rakha EA, Elsheikh SE, Aleskandarany MA, Habashi HO, Green AR, Powe DG, El-Sayed ME, Benhasouna A, Brunet JS, Akslen LA, Evans AJ, Blamey R, Reis-Filho JS, Foulkes WD, Ellis IO. Triple-negative breast cancer: Distinguishing between basal and nonbasal subtypes. Clin Cancer Res. 2009; 15:2302-10.

8. Hasebe T, Iwasaki M, Akashi-Tanaka S, Hojo T, Shibata T, Kinoshita T, Tsuda H. Important histologic outcome predictors for patients with invasive ductal carcinoma of the breast. Am J Surg Pathol. 2011;35:1484-97.

9. Onitilo AA, Engel JM, Greenlee RT, Mukesh BN. Breast cancer subtypes based on ER/PR and Her2 expression: Comparison of clinicopathologic features and survival. Clinical Medicine & Research. 2009;7:(1-2)4-13.

10. Blackwell KL, Dewhirst MW, Liotcheva V, Snyder S, Broadwater G, Bentley R, Lal A, Riggins G, Anderson S, Vredenburgh J, Proia A, Harris LN. HER-2 gene amplification correlates with higher levels of angiogenesis and lower levels of hypoxia in primary breast tumors. Clin Cancer Res. 2004;10:4083-8.

11. Dimmeler S, Zeiher AM. Akt takes center stage in angiogenesis signaling. Circ Res. 2000;86:4-5.

12. Zhang GH, Yang WT, Zhou XY, Zeng Y, Lu H-F, Shi DR. Study of the correlation between HER-2 gene and lymphangiogenesis and their prognostic significance in human breast cancer. Zhonghua Yi Xue Za Zhi. 2007;87:155-60.

13. Schoppmann SF, Tamandl D, Roberts L, Jomrich G, Schoppmann A, Zwrtek R, Dubsky P, Gnant M, Jakesz R, Birner P. HER2/neu expression correlates with vascular endothelial growth factor-C and lymphangiogenesis in lymph node-positive breast cancer. Ann Oncol. 2009;21:955-60.

14. Raica M, Cimpean AM, Ceausu R, Ribatti D. Lymphatic microvessel density, VEGF-C, and VEGFR-3 expression in different molecular types of breast cancer. Anticancer Res. 2011;31:1757-64.

15. Tavassoli FA, Devillee P. WHO Classification of Tumours: Pathology and genetics of tumours of the breast and female genital organs, Lyon: IARC Press; 2003. 11-58.

16. E lston CW, Ellis IO. Pathological prognostic factors in breast cancer. The value of histological grade in breast cancer: Experience from a large study with long-term follow-up. Histopathology. 2002;41:154-61.

17. Wolff AC, Hammond MEH, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, American Society of Clinical Oncology/College of American Pathologists. Guideline recommendations for Human Epidermal Growth Factor Receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131:18-34.

18. Dowsett M, Allred C, Knox J, Quinn E, Salter J, Wale C, Cuzick J, Houghton J, Williams N, Mallon E, Bishop H, Ellis I, Larsimont D, Sasano H, Carder P, Llombart Cussac A, Knox F, Speirs V, Forbes J, Buzdar A. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, alone or in combination trial. J Clin Oncol. 2008;26:1059-65.

19. Cunnick GH, Jiang WG, Douglas-Jones T, Watkins G, Gomez KF, Morgan MJ, Subramanian A, Mokbel K, Mansel RE. Lymphangiogenesis and lymph node metastasis in breast cancer. Mol Cancer. 2008;7:23.

20. Karpanen T, Egeblad M, Karkkainen MJ, Kubo H, Yla-Herttuala S, Jaattela M, Alitalo K. Vascular Endothelial Growth Factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res. 2001;61:1786-90.

21. van der Auwera I, Van den Eynden G, Colpaert C, Van Laere S, van Dam P, Van Marck E, Dirix L, Vermeulen P. Tumor lymphangiogenesis in inflammatory breast carcinoma: A histomorphometric study. Clin Cancer Res. 2005;11:7637-42.

22. Agarwal B, Saxena R, Morimiya A, Mehrotra S, Badve S. Lymphangiogenesis does not occur in breast cancer. Am J Surg Pathol. 2005;29:1449-55.

23. V leugel M, Bos R, van der Groep P, Greijer A E, Shvarts A, Stel HV, van der Wall E, van Diest PJ. Lack of lymphangiogenesis during breast carcinogenesis. J Clin Pathol. 2004;57:746-51.

24. Williams C, Leek R, Robson A, Banerji S, Prevo R, Harris A, Jackson D. Absence of lymphangiogenesis and intratumoural lymph vessels in human metastatic breast cancer. J Pathol. 2003;200:195-206.

25. Hammond MEH, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FCG, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer (Unabridged Version). Arch Pathol Lab Med. 2010;134:e48-e72.

26. E lkin M, Orgel A, Kleinman HK An angiogenic switch in breast cancer involves estrogen and soluble vascular endothelial growth factor receptor 1. J Natl Cancer Inst 2004;96:875-8.

27. Alitalo A, Detmar M. Interaction of tumor cells and lymphatic vessels in cancer progression. Oncogene. 2012;31:4499-508.

28. L ee K, Park do J, Choe G, Kim HH, Kim WH, Lee HS. Increased intratumoral lymphatic vessel density correlates with lymph node metastasis in early gastric carcinoma. Ann Surg Oncol. 2010;17:73-80.

Turkish Journal of Pathology

The Journal of Federation of Turkish Pathology Societies 

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Cite Score 2018: 0.88

SCImago Journal Rank (SJR) 2018: 0.3
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