Triple-negative breast cancer is associated with EGFR, CK5/6 and c-KIT expression in Malaysian women

BMC Clinical Pathology

Chee-Onn Leong²  Suseela Nair³  Annie Tay¹  Shant Kishen Kanapathy Pillai¹ 

[1] School of Medicine, International Medical University, Bukit Jalil, Kuala Lumpur, 57000, Malaysia;International Medical University, 126 Jalan 19/155B, Bukit Jalil, Kuala Lumpur, 57000, Malaysia;Gleneagles Hospital Kuala Lumpur, 282 & 286 Jalan Ampang, Kuala Lumpur, 50450, Malaysia

关键词: c-Kit;    CK5/6;    EGFR;    Basal-like;    Triple-negative breast cancers;   

Others  :  1085290
DOI  :  10.1186/1472-6890-12-18

 received in 2011-12-15, accepted in 2012-09-24,  发布年份 2012

【 摘 要 】

Background

Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer characterized by the lack of estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) expressions. This subgroup of refractory disease tends to have aggressive clinical behavior, high frequency of metastasis and lack of response to current hormonal or targeted therapies. Despite numerous studies reporting the clinicopathological features of TNBC and its association with the basal-like phenotype in the Western population, only limited data are available in the Asian population. Therefore, the aim of this study was to investigate the clinicopathological characteristics of TNBC and its association with epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6) and mast/stem cell growth factor receptor (c-KIT or CD117) expression in Malaysian women.

Methods

A total of 340 patients diagnosed with primary breast cancer between 2002 and 2006 in Malaysia were reviewed and analyzed.

Results

The incidence of TNBC was 12.4% (42/340). Bivariate analysis revealed that TNBC was strongly associated with a younger age, higher grade tumor and p53 expression. Further immunohistochemical analysis suggested that TNBC in Malaysian women was strongly associated with EGFR, CK5/6 and c-KIT expression with high a Ki-67 proliferation index.

Conclusion

In conclusion, our study confirms the association of TNBC with basal-like marker expression (EGFR, CK5/6 and c-KIT) in Malaysian women, consistent with studies in other populations.

【 授权许可】

   
2012 Kanapathy Pillai et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al.: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001, 98(19):10869-10874.
• [2]Loi S, Piccart M, Sotiriou C: The use of gene-expression profiling to better understand the clinical heterogeneity of estrogen receptor positive breast cancers and tamoxifen response. Crit Rev Oncol Hematol 2007, 61(3):187-194.
• [3]van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, et al.: A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002, 347(25):1999-2009.
• [4]Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, et al.: Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003, 100(14):8418-8423.
• [5]Sotiriou C, Piccart MJ: Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care? Nat Rev Cancer 2007, 7(7):545-553.
• [6]Leong CO, Vidnovic N, DeYoung MP, Sgroi D, Ellisen LW: The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers. J Clin Invest 2007, 117(5):1370-1380.
• [7]Lim LY, Vidnovic N, Ellisen LW, Leong CO: Mutant p53 mediates survival of breast cancer cells. Br J Cancer 2009, 101(9):1606-1612.
• [8]Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, et al.: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004, 10(16):5367-5374.
• [9]Reis-Filho JS, Tutt AN: Triple negative tumours: a critical review. Histopathology 2008, 52(1):108-118.
• [10]Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, et al.: Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 2005, 11(16):5678-5685.
• [11]Lund MJ, Trivers KF, Porter PL, Coates RJ, Leyland-Jones B, Brawley OW, Flagg EW, O'Regan RM, Gabram SG, Eley JW: Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res Treat 2009, 113(2):357-370.
• [12]Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, et al.: Race, breast cancer subtypes, and survival in the Carolina breast cancer study. JAMA 2006, 295(21):2492-2502.
• [13]Cunningham JE, Montero AJ, Garrett-Mayer E, Berkel HJ, Ely B: Racial differences in the incidence of breast cancer subtypes defined by combined histologic grade and hormone receptor status. Cancer Causes Control 2009, 21(3):399-409.
• [14]Thike AA, Cheok PY, Jara-Lazaro AR, Tan B, Tan P, Tan PH: Triple-negative breast cancer: clinicopathological characteristics and relationship with basal-like breast cancer. Mod Pathol 2009, 23(1):123-133.
• [15]Kim MJ, Ro JY, Ahn SH, Kim HH, Kim SB, Gong G: Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol 2006, 37(9):1217-1226.
• [16]Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong CO, Calogrias D, Buraimoh A, et al.: Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol 2010, 28(7):1145-1153.
• [17]Lamy PJ, Fina F, Bascoul-Mollevi C, Laberenne AC, Martin PM, Ouafik L, Jacot W: Quantification and clinical relevance of gene amplification at chromosome 17q12-q21 in human epidermal growth factor receptor 2-amplified breast cancers. Breast Cancer Res 2012, 13(1):R15.
• [18]Sauter G, Lee J, Bartlett JM, Slamon DJ, Press MF: Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol 2009, 27(8):1323-1333.
• [19]Livasy CA, Karaca G, Nanda R, Tretiakova MS, Olopade OI, Moore DT, Perou CM: Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 2006, 19(2):264-271.
• [20]Aleskandarany MA, Rakha EA, Macmillan RD, Powe DG, Ellis IO, Green AR: MIB1/Ki-67 labelling index can classify grade 2 breast cancer into two clinically distinct subgroups. Breast Cancer Res Treat 2010, 127(3):591-599.
• [21]Weidner N, Moore DH 2nd, Vartanian R: Correlation of Ki-67 antigen expression with mitotic figure index and tumor grade in breast carcinomas using the novel "paraffin"-reactive MIB1 antibody. Hum Pathol 1994, 25(4):337-342.
• [22]Jalava P, Kuopio T, Juntti-Patinen L, Kotkansalo T, Kronqvist P, Collan Y: Ki67 immunohistochemistry: a valuable marker in prognostication but with a risk of misclassification: proliferation subgroups formed based on Ki67 immunoreactivity and standardized mitotic index. Histopathology 2006, 48(6):674-682.
• [23]Rhee J, Han SW, Oh DY, Kim JH, Im SA, Han W, Park IA, Noh DY, Bang YJ, Kim TY: The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer. BMC Cancer 2008, 8:307. BioMed Central Full Text
• [24]Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al.: Molecular portraits of human breast tumours. Nature 2000, 406(6797):747-752.
• [25]Rakha EA, Aleskandarany M, El-Sayed ME, Blamey RW, Elston CW, Ellis IO, Lee AH: The prognostic significance of inflammation and medullary histological type in invasive carcinoma of the breast. Eur J Cancer 2009, 45(10):1780-1787.
• [26]Cheang MC, 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(5):1368-1376.
• [27]Turner N, Tutt A, Ashworth A: Hallmarks of 'BRCAness' in sporadic cancers. Nat Rev Cancer 2004, 4(10):814-819.
• [28]Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, et al.: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001, 344(11):783-792.
• [29]Kwan ML, Kushi LH, Weltzien E, Maring B, Kutner SE, Fulton RS, Lee MM, Ambrosone CB, Caan BJ: Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res 2009, 11(3):R31. BioMed Central Full Text
• [30]Bertucci F, Finetti P, Cervera N, Esterni B, Hermitte F, Viens P, Birnbaum D: How basal are triple-negative breast cancers? Int J Cancer 2008, 123(1):236-240.
• [31]Bidard FC, Conforti R, Boulet T, Michiels S, Delaloge S, Andre F: Does triple-negative phenotype accurately identify basal-like tumour? An immunohistochemical analysis based on 143 'triple-negative' breast cancers. Ann Oncol 2007, 18(7):1285-1286.
• [32]Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V: Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 2007, 109(9):1721-1728.
• [33]Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM: The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 2007, 13(8):2329-2334.
• [34]Cleator S, Heller W, Coombes RC: Triple-negative breast cancer: therapeutic options. Lancet Oncol 2007, 8(3):235-244.
• [35]Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA: Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007, 13(15 Pt 1):4429-4434.
• [36]Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, Harris L, Hait W, Toppmeyer D: Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 2006, 24(36):5652-5657.
• [37]Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO: Prognostic markers in triple-negative breast cancer. Cancer 2007, 109(1):25-32.
• [38]Tan GH, Taib NA, Choo WY, Teo SH, Yip CH: Clinical characteristics of triple-negative breast cancer: experience in an Asian developing country. Asian Pac J Cancer Prev 2009, 10(3):395-398.
• [39]Teoh KH, Looi LM, Sabaratnam S, Cheah PL, Nazarina AR, Mun KS: An analysis of predictive biomarkers in routine histopathological reporting of infiltrating ductal breast carcinoma in a tertiary hospital in Malaysia with a focus on limitations and directions for future development. Malays J Pathol 2011, 33(1):35-42.
• [40]Iwase H, Kurebayashi J, Tsuda H, Ohta T, Kurosumi M, Miyamoto K, Yamamoto Y, Iwase T: Clinicopathological analyses of triple negative breast cancer using surveillance data from the registration committee of the Japanese breast cancer society. Breast Cancer 2009, 17(2):118-124.
• [41]Tian XS, Cong MH, Zhou WH, Zhu J, Chen YZ, Liu Q: Clinicopathologic and prognostic characteristics of triple-negative breast cancer. Onkologie 2008, 31(11):610-614.
• [42]Brenton JD, Carey LA, Ahmed AA, Caldas C: Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 2005, 23(29):7350-7360.
• [43]Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, van de Vijver MJ: Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 2007, 9(5):R65. BioMed Central Full Text
• [44]Lachapelle J, Foulkes WD: Triple-negative and basal-like breast cancer: implications for oncologists. Curr Oncol 2011, 18(4):161-164.