Aberrant expression of E-cadherin in infiltrating ductal and lobular breast carcinomas and its correlation with clinicopathological parameters – A hospital-based study
Abstract
Introduction: Breast carcinoma is one of the commonest malignant tumours in women, leading to premature deaths and morbidity. E-cadherin is a 120kDa calcium-dependent transmembrane glycoprotein encoded by the CDH1 gene located on chromosome 16q21 and is expressed in most epithelial cells. Loss of E Cadherin expression implies cell discohesion and favours metastasis. The study aims to evaluate the expression of E-cadherin in breast carcinoma and its association with various histomorphological and clinicopathological parameters.
Materials and Methods : A total of 30 cases of breast carcinomas were studied, over two years. Histological grade and type were assessed by staining the paraffin-embedded sections with H & E. Using IHC technique, E-cadherin antigen was retrieved by Heat-Induced Epitome Retrieval method, and immunostaining was scored semiquantitatively. Cases were grouped as ‘preserved,’ when positivity was strong membranous, and occurred in more than 75% of the neoplastic epithelial cells and ‘aberrant’ in all the remaining cases. The scores were then correlated with the histopathological grade, histological type of tumour and clinicopathological parameters.
Results: E-cadherin was found to be preserved in 46.7% of all the breast carcinomas and aberrant in 51.7% of invasive ductal carcinomas (IDC) alone, while 100% of invasive lobular carcinomas showed aberrant expression. No significant correlation was found with E-cadherin grading and histological type of carcinoma, histopathological grade or involvement of deep surgical margin.
Conclusion: Differentiation between invasive ductal and invasive lobular carcinoma based on the loss of E-cadherin has to be done cautiously given its aberrant expression in ductal carcinomas as well.
Downloads
References
Rosai J. Breast In:Rosai and Ackerman’s surgical pathology. 9th ed. Philadelphia:Churchill Livingston:2004.p.1787.
Raj P. Review of cancer statistics in India. International Journal of Advances in Signal and Image Sciences. 2015 Jan 29;1(1):1-4.
Ahmad Z, Khurshid A, Qureshi A, Idress R, Asghar N, Kayani N. Breast carcinoma grading, estimation of tumor size, axillary lymph node status, staging, and nottingham prognostic index scoring on mastectomy specimens. Indian J PatholMicrobiol. 2009 Oct-Dec;52(4):477-81. doi: 10.4103/0377-4929.56123.
Lari SA, Kuerer HM. Biological Markers in DCIS and Risk of Breast Recurrence: A Systematic Review. J Cancer. 2011 May 1;2:232-61. doi: 10.7150/jca.2.232.
Symmers, W. C. "Assessment of histological grade." Edinburgh, United Kingdom, Churchill Livingstone (1998).
Pereira H, Pinder SE, Sibbering DM, Galea MH, Elston CW, Blamey RW, et al. Pathological prognostic factors in breast cancer. IV: Should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma. Histopathology. 1995 Sep;27(3):219-26. doi: 10.1111/j.1365-2559.1995.tb00213.x.
Sundquist M, Thorstenson S, Brudin L, Nordenskjöld B. Applying the Nottingham Prognostic Index to a Swedish breast cancer population. South East Swedish Breast Cancer Study Group. Breast Cancer Res Treat. 1999 Jan;53(1):1-8. doi: 10.1023/a:1006052115874.
Ugnat AM, Xie L, Morriss J, Semenciw R, Mao Y. Survival of women with breast cancer in Ottawa, Canada: variation with age, stage, histology, grade and treatment. Br J Cancer. 2004 Mar 22;90(6):1138-43. doi: 10.1038/sj.bjc.6601662.
Dalton LW, Page DL, Dupont WD. Histologic grading of breast carcinoma. A reproducibility study. Cancer. 1994 Jun 1;73(11):2765-70.doi:10.1002/1097-0142(19940601)73:11<2765::aid-cncr2820731119>3.0.co;2-k.
Bloom Hj, Richardson Ww. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer. 1957 Sep;11(3):359-77. doi: 10.1038/bjc.1957.43.
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403-10. doi: 10.1111/j.1365-2559.1991.tb00229.x.
Genestie C, Zafrani B, Asselain B, Fourquet A, Rozan S, Validire P, et al. Comparison of the prognostic value of Scarff-Bloom-Richardson and Nottingham histological grades in a series of 825 cases of breast cancer: major importance of the mitotic count as a component of both grading systems. Anticancer Res. 1998 Jan-Feb;18(1B):571-6.
Ellis IO, Pinder SE, Lee AHS. Tumours of the breast. In: Fletcher CDM, editor. Diagnostic histopathology of tumours. 3rd ed., Philadelphia: Churchill Livingston; 2007.p.903-60
Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991 Mar 22;251(5000):1451-5. doi: 10.1126/science.2006419.
Okegawa T, Pong RC, Li Y, Hsieh JT. The role of cell adhesion molecule in cancer progression and its application in cancer therapy. Acta Biochim Pol. 2004;51(2):445-57.
Umbas R, Isaacs WB, Bringuier PP, Schaafsma HE, Karthaus HF, Oosterhof GO, Debruyne FM, Schalken JA. Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res. 1994 Jul 15;54(14):3929-33.
Batistatou A, Peschos D, Tsanou H, Charalabopoulos A, Nakanishi Y, Hirohashi S, et al. In breast carcinoma dysadherin expression is correlated with invasiveness but not with E-cadherin. Br J Cancer. 2007 May 7;96(9):1404-8. doi: 10.1038/sj.bjc.6603743.
Charpin C, Garcia S, Bonnier P, Martini F, Andrac L, Choux R, et al. Reduced E-cadherin immunohistochemical expression in node-negative breast carcinomas correlates with 10-year survival. Am J Clin Pathol. 1998 Apr;109(4):431-8. doi: 10.1093/ajcp/109.4.431.
De Leeuw WJ, Berx G, Vos CB, Peterse JL, Van de Vijver MJ, Litvinov S, et al. Cleton-Jansen AM. Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol. 1997 Dec;183(4):404-11. doi: 10.1002/(SICI)1096-9896(199712)183:4<404::AID-PATH1148>3.0.CO;2-9.
Female Reproductive System. In: Young B, Lowe JS, Stevens A, HeathJW, editors.Wheater’s functional histology. A text and colour atlas.5thed, Churchill Livingstone, Elseveir;2009:359-391.
Zafrani B, Aubriot MH, Mouret E, De Crémoux P, De Rycke Y, Nicolas A, et al. High sensitivity and specificity of immunohistochemistry for the detection of hormone receptors in breast carcinoma: comparison with biochemical determination in a prospective study of 793 cases. Histopathology. 2000 Dec;37(6):536-45. doi: 10.1046/j.1365-2559.2000.01006.x.
Siitonen SM, Kononen JT, Helin HJ, Rantala IS, Holli KA, Isola JJ. Reduced E-cadherin expression is associated with invasiveness and unfavorable prognosis in breast cancer. Am J Clin Pathol. 1996 Apr;105(4):394-402. doi: 10.1093/ajcp/105.4.394.
Pai K, Baliga P, Shrestha BL. E-cadherin expression: a diagnostic utility for differentiating breast carcinomas with ductal and lobular morphologies. J Clin Diagn Res. 2013 May;7(5):840-4. doi: 10.7860/JCDR/2013/5755.2954.
Esposito NN, Chivukula M, Dabbs DJ. The ductal phenotypic expression of the E-cadherin/catenin complex in tubulolobular carcinoma of the breast: an immunohistochemical and clinicopathologic study. Mod Pathol. 2007 Jan;20(1):130-8. doi: 10.1038/modpathol.3800721.
Friedl P, Hegerfeldt Y, Tusch M. Collective cell migration in morphogenesis and cancer. Int J Dev Biol. 2004;48(5-6):441-9. doi: 10.1387/ijdb.041821pf.
Kowalski PJ, Rubin MA, Kleer CG. E-cadherin expression in primary carcinomas of the breast and its distant metastases. Breast Cancer Res. 2003;5(6):R217-22. doi: 10.1186/bcr651.
Munjal K, Ambaye A, Evans MF, Mitchell J, Nandedkar S, Cooper K. Immunohistochemical analysis of ER, PR, Her2 and CK5/6 in infiltrative breast carcinomas in Indian patients. Asian Pac J Cancer Prev. 2009;10(5):773-8.
Ambroise M, Ghosh M, Mallikarjuna VS, Kurian A. Immunohistochemical profile of breast cancer patients at a tertiary care hospital in South India. Asian Pac J Cancer Prev. 2011;12(3):625-9.
Raina V, Bhutani M, Bedi R, Sharma A, Deo SV, Shukla NK, et al. Rath GK. Clinical features and prognostic factors of early breast cancer at a major cancer center in North India. Indian J Cancer. 2005 Jan-Mar;42(1):40-5. doi: 10.4103/0019-509x.15099.
Pervin, Mosammat Mira, et al. "Study on Clinical Presentation of Breast Carcinoma of 50 Cases." Chattagram Maa-O-Shishu Hospital Medical College Journal 13.2 (2014): 8-11.
Azizun-Nisa, Bhurgri Y, Raza F, Kayani N. Comparison of ER, PR and HER-2/neu (C-erb B 2) reactivity pattern with histologic grade, tumor size and lymph node status in breast cancer. Asian Pac J Cancer Prev. 2008 Oct-Dec;9(4):553-6.
Meena SP, Hemrajani DK, Joshi N. A comparative and evaluative study of cytological and histological grading system profile in malignant neoplasm of breast--an important prognostic factor. Indian J Pathol Microbiol. 2006 Apr;49(2):199-202. Erratum in: Indian J Pathol Microbiol. 2006 Jul;49(3):476.
Costa MJ, Tadros T, Hilton G, Birdsong G. Breast fine needle aspiration cytology. Utility as a screening tool for clinically palpable lesions. Acta Cytol. 1993 Jul-Aug;37(4):461-71.
Joshi K, Mehtani VG, Mehrotra GC. The pathologic profile of invasive breast cancer I. Factors intrinsic to the tumour. Indian J Cancer. 1983 Jan-Feb;20(1):15-22.
Ayadi L, Khabir A, Amouri H, Karray S, Dammak A, Guermazi M, et al. Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma. World J Surg Oncol. 2008 Oct 22;6:112. doi: 10.1186/1477-7819-6-112.
Satti MB. Oestrogen receptor/progesterone receptor and human epidermal growth factor receptor 2 status in breast cancer: a 9-year study at Princess Noorah Oncology Center, Saudi Arabia. Histopathology. 2011 Sep;59(3):537-42. doi: 10.1111/j.1365-2559.2011.03883.x.
Onitilo AA, Engel JM, Greenlee RT, Mukesh BN. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res. 2009 Jun;7(1-2):4-13. doi: 10.3121/cmr.2009.825.
Sekar P, Bharti JN, Nigam JS, Sharma A, Soni PB. Evaluation of p53, HoxD10, and E-Cadherin Status in Breast Cancer and Correlation with Histological Grade and Other Prognostic Factors. J Oncol. 2014;2014:702527. doi: 10.1155/2014/702527.
Sauer T, Boudjema G, Jebsen PW, Naess O. Immunocytochemical expression of E-cadherin on fine-needle aspirates from breast carcinomas correlate with the cell dissociation pattern seen on smears. Diagn Cytopathol. 2001 Dec;25(6):382-8. doi: 10.1002/dc.10030.
Horne HN, Sherman ME, Garcia-Closas M, Pharoah PD, Blows FM, Yang XR, et al. Breast cancer susceptibility risk associations and heterogeneity by E-cadherin tumor tissue expression. Breast Cancer Res Treat. 2014 Jan;143(1):181-7. doi: 10.1007/s10549-013-2771-z.
Copyright (c) 2021 Author (s). Published by Siddharth Health Research and Social Welfare Society
This work is licensed under a Creative Commons Attribution 4.0 International License.
OAI - Open Archives Initiative
