ORIGINAL ARTICLE
Incorporating immunohistochemical markers into screening methods for BRCA1-mutated breast cancer
1
Students’ Scientific Organization of Cancer Cell Biology, Department of Cancer Prevention, Medical University of Warsaw, Warsaw, Poland
2
Department of Cancer Prevention, Medical University of Warsaw, Warsaw, Poland
Submission date: 2019-03-21
Final revision date: 2019-08-25
Acceptance date: 2019-10-06
Publication date: 2020-10-25
Pol J Pathol 2020;71(3):261-269
KEYWORDS
TOPICS
ABSTRACT
BRCA1-mutated breast cancer (BC) is responsible for approximately 25% of hereditary breast cancer cases. BRCA1 is a tumor suppressor protein regulating the cell cycle and DNA repair; therefore its dysfunctions play a significant role in carcinogenesis. BRCA1-mutated BC is associated with basal-like phenotype, lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in addition to frequent TP53 mutations and poor prognosis. Currently used criteria for genetic evaluation of BC for the risk of hereditary mutations are based on patients’ age and family history, and therefore are prone to be imprecise or incomplete. This review discusses recently developed sets of immunohistochemical markers, promising independent markers (nestin, ALDH1, FOXO3, claudins, topoisomerase 1, EGFR) and their potential to be incorporated into clinical practice as a support tool in oncological counseling. This approach could be applied as a screening method for cost-effective selection of cases requiring genetic testing or adapted in pathology laboratories with limited access to molecular techniques. Although not all of the described predictor models have been validated yet, they could further improve the performance of BRCA1 screening methods in BC in the near future via increasing the accuracy of criteria for further genetic evaluation.
REFERENCES (101)
1.
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.
2.
Larsen MJ, Thomassen M, Gerdes A-M, et al. Hereditary breast cancer: clinical, pathological and molecular characteristics. Breast Cancer (Auckl) 2014; 8: 145-155.
3.
Rojas K, Stuckey A. Breast Cancer Epidemiology and risk factors. Clin Obstet Gynecol 2016; 59: 651-672.
4.
Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007; 25: 1329-1333.
5.
Somasundaram K. Breast cancer gene 1 (BRCA1): role in cell cycle regulation and DNA repair – perhaps through transcription. J Cell Biochem 2003; 88: 1084-1091.
6.
Honrado E, Benítez J, Palacios J. Histopathology of BRCA1- and BRCA2-associated breast cancer. Crit Rev Oncol Hematol 2006; 59: 27-39.
7.
Schmidt MK, van den Broek AJ, Tollenaar RAEM, et al. Breast cancer survival of BRCA1/BRCA2 mutation carriers in a hospital-based cohort of young women. J Natl Cancer Inst 2017; 109.
8.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast and Ovarian. https://www.nccn.org/professio.... Accessed 05 Mar 2019.
9.
Hartman A-R, Kaldate RR, Sailer LM, et al. Prevalence of BRCA mutations in an unselected population of triple-negative breast cancer. Cancer 2012; 118: 2787-2795.
10.
Grindedal EM, Heramb C, Karsrud I, et al. Current guidelines for BRCA testing of breast cancer patients are insufficient to detect all mutation carriers. BMC Cancer 2017; 17: 438.
11.
Stolnicu S, Bauer O, Naznean A, et al. ER–/PR+ subset of invasive breast carcinoma (IBC): a distinct phenotype with good prognosis. Pol J Pathol 2018; 69: 311-313.
12.
Adamkov M, Drahošová S, Chylíková J, et al. Survivin in breast lesions: immunohistochemical analysis of 196 cases. Pol J Pathol 2017; 68: 297-305.
13.
Mokrý J, Cízková D, Filip S, et al. Nestin expression by newly formed human blood vessels. Stem Cells Dev 2004; 13: 658-664.
14.
Lendahl U, Zimmerman LB, McKay RDG. CNS stem cells express a new class of intermediate filament protein. Cell 1990; 60: 585-595.
15.
Sejersen T, Lendahl U. Transient expression of the intermediate filament nestin during skeletal muscle development. J Cell Sci 19993; 106 (Pt 4): 1291-1300.
16.
Li H, Cherukuri P, Li N, et al. Nestin is expressed in the basal/myoepithelial layer of the mammary gland and is a selective marker of basal epithelial breast tumors. Cancer Res 2007; 67: 501-510.
17.
Krum JM, Rosenstein JM. Transient coexpression of nestin, GFAP, and vascular endothelial growth factor in mature reactive astroglia following neural grafting or brain wounds. Exp Neurol 1999; 160: 348-360.
18.
Vaittinen S, Lukka R, Sahlgren C, et al. The expression of intermediate filament protein Nestin as related to vimentin and desmin in regenerating skeletal muscle. J Neuropathol Exp Neurol 2001; 60: 588-597.
19.
Ishiwata T, Matsuda Y, Naito Z. Nestin in gastrointestinal and other cancers: Effects on cells and tumor angiogenesis. World J Gastroenterol 2011; 17: 409-418.
20.
Yang XH, Wu QL, Yu XB, et al. Nestin expression in different tumours and its relevance to malignant grade. J Clin Pathol 2008; 61: 467-473.
21.
Neradil J, Veselska R. Nestin as a marker of cancer stem cells. Cancer Sci 2015; 106: 803-811.
22.
Ehrmann J, Kolár Z, Mokry J. Nestin as a diagnostic and prognostic marker: Immunohistochemical analysis of its expression in different tumours. J Clin Pathol 2005; 58: 222-223.
23.
Asleh K, Won JR, Gao D, et al. Nestin expression in breast cancer: Association with prognosis and subtype on 3641 cases with long-term follow-up. Breast Cancer Res Treat 2018; 168: 107-115.
24.
Krüger K, Wik E, Knutsvik G, et al. Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer. Sci Rep 2017; 7: 1089.
25.
Ginestier C, Wicinski J, Cervera N, et al. Retinoid signaling regulates breast cancer stem cell differentiation. Cell Cycle 2009; 8: 3297-3302.
26.
Lindahl R. Aldehyde dehydrogenases and their role in carcinogenesis. Crit Rev Biochem Mol Biol 1992; 27: 283-335.
27.
Januchowski R, Wojtowicz K, Zabel M. The role of aldehyde dehydrogenase (ALDH) in cancer drug resistance. Biomed Pharmacother 2013; 67: 669-680.
28.
Sládek NE. Human aldehyde dehydrogenases: potential pathological, pharmacological, and toxicological impact. J Biochem Mol Toxicol 2003; 17: 7-23.
29.
Sládek NE, Kollander R, Sreerama L, et al. Cellular levels of aldehyde dehydrogenases (ALDH1A1 and ALDH3A1) as predictors of therapeutic responses to cyclophosphamide-based chemotherapy of breast cancer: a retrospective study. Rational individualization of oxazaphosphorine-based cancer chemotherapeutic regimens. Cancer Chemother Pharmacol 2002; 49: 309-321.
30.
Tanei T, Morimoto K, Shimazu K, et al. Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast cancers. Clin Cancer Res 2009; 15: 4234-4241.
31.
Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007; 1: 555-567.
32.
Zhou L, Jiang Y, Yan T, et al. The prognostic role of cancer stem cells in breast cancer: a meta-analysis of published literatures. Breast Cancer Res Treat 2010; 122: 795-801.
33.
Liu S, Ginestier C, Charafe-Jauffret E, et al. BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci U S A 2008; 105: 1680-1685.
34.
Madjd Z, Ramezani B, Molanae S, et al. High Expression of stem cell marker ALDH1 is associated with reduced BRCA1 in invasive breast carcinomas. Asian Pac J Cancer Prev 2012; 13: 2973-2978.
35.
van Heerma Voss MR, van der Groep P, Bart J, et al. Expression of the stem cell marker ALDH1 in BRCA1 related breast cancer. Cell Oncol (Dordr) 2011; 34: 3-10.
36.
van Heerma Voss MR, van der Groep P, Bart J, et al. Expression of the stem cell marker ALDH1 in the normal breast of BRCA1 mutation carriers. Breast Cancer Res 2010; Treat 123: 611-612.
37.
Bane A, Viloria-Petit A, Pinnaduwage D, et al. Clinical-pathologic significance of cancer stem cell marker expression in familial breast cancers. Breast Cancer Res Treat 2013; 140: 195-205.
38.
Myatt SS, Lam EW-F. The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer 2007; 7: 847-859.
39.
McGovern UB, Francis RE, Peck B, et al. Gefitinib (Iressa) represses FOXM1 expression via FOXO3a in breast cancer. Mol Cancer Ther 2009; 8: 582-591.
40.
Park S-H, Chung YM, Ma J, et al. Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo. Oncotarget 2016; 7: 42110-42125.
41.
Hu T, Chung YM, Guan M, et al. Reprogramming ovarian and breast cancer cells into non-cancerous cells by low-dose metformin or SN-38 through FOXO3 activation. Sci Rep 2014; 4: 5810.
42.
Wolfe AR, Debeb BG, Lacerda L, et al. Simvastatin prevents triple-negative breast cancer metastasis in pre-clinical models through regulation of FOXO3a. Breast Cancer Res Treat 2015; 154: 495-508.
43.
Jiang Y, Zou L, Lu W-Q, et al. Foxo3a expression is a prognostic marker in breast cancer. PLoS One 2013; 8: e70746.
44.
Habashy HO, Rakha EA, Aleskandarany M, et al. FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer. Breast Cancer Res Treat 2011; 129: 11-21.
45.
Zou Y, Tsai W-B, Cheng C-J, et al. Forkhead box transcription factor FOXO3a suppresses estrogen-dependent breast cancer cell proliferation and tumorigenesis. Breast Cancer Res 2008; 10: R21.
46.
Sauvageau M, Sauvageau G. Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer. Cell Stem Cell 2010; 7: 299-313.
47.
Cao R, Wang L, Wang H, et al. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 2002; 298: 1039-1043.
48.
Kleer CG, Cao Q, Varambally S, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A 2003; 100: 11606-11611.
49.
Gong C, Yao S, Gomes AR, et al. BRCA1 positively regulates FOXO3 expression by restricting FOXO3 gene methylation and epigenetic silencing through targeting EZH2 in breast cancer. Oncogenesis 2016; 5: e214.
50.
Angelow S, Ahlstrom R, Yu ASL. Biology of claudins. Am J Physiol Renal Physiol 2008; 295: F867-F876.
51.
Lanigan F, McKiernan E, Brennan DJ, et al. Increased claudin-4 expression is associated with poor prognosis and high tumour grade in breast cancer. Int J Cancer 2009; 124: 2088-2097.
52.
Krause G, Winkler L, Mueller SL, et al. Structure and function of claudins. Biochim Biophys Acta 2008; 1778: 631-645.
53.
Tabariès S, Siegel PM. The role of claudins in cancer metastasis. Oncogene 2017; 36: 1176-1190.
54.
Osanai M, Takasawa A, Murata M, et al. Claudins in cancer: bench to bedside. Pflugers Arch 2017; 469: 55-67.
55.
Danzinger S, Tan YY, Rudas M, et al. Differential claudin 3 and EGFR expression predicts BRCA1 mutation in triple-negative breast cancer. Cancer Invest 2018; 36: 378-388.
57.
Distinct claudin expression characterizes BRCA1-related breast cancer. Histopathology 2014; 65: 814-827.
58.
Wang JC. Interaction between DNA and an Escherichia coli protein ω. J Mol Biol 1971; 55: 523-533.
59.
Champoux JJ. DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem 2001; 70: 369-413.
60.
Lee MP, Brown SD, Chen A, et al. DNA topoisomerase I is essential in Drosophila melanogaster. Proc Natl Acad Sci U S A 1993; 90: 6656-6660.
61.
Kollmannsberger C, Mross K, Jakob A, et al. Topotecan – A novel topoisomerase I inhibitor: pharmacology and clinical experience. Oncology 1999; 56: 1-12.
65.
Shimoyama Y, Hirohashi S, Hirano S, et al. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer Res 1989; 49: 2128-2133.
66.
Kovács A, Walker RA. P-cadherin as a marker in the differential diagnosis of breast lesions. J Clin Pathol 2003; 56: 139-141.
67.
Paredes J, Stove C, Stove V, et al. P-cadherin is up-regulated by the antiestrogen ICI 182,780 and promotes invasion of human breast cancer cells. Cancer Res 2004; 64: 8309-8317.
68.
Paredes J, Albergaria A, Oliveira JT, et al. P-cadherin overexpression is an indicator of clinical outcome in invasive breast carcinomas and is associated with CDH3 promoter hypo-methylation. Clin Cancer Res 2005; 11: 5869-5877.
69.
Turashvili G, McKinney SE, Goktepe O, et al. P-cadherin expression as a prognostic biomarker in a 3992 case tissue microarray series of breast cancer. Mod Pathol 2011; 24: 64-81.
70.
Mannello F, Tonti GAM, Medda V, et al. Increased shedding of soluble fragments of P-cadherin in nipple aspirate fluids from women with breast cancer. Cancer Sci 2008; 99: 2160-2169.
71.
Arnes JB, Brunet J-S, Stefansson I, et al. Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer. Clin Cancer Res 2005; 11: 4003-4011.
72.
Gorski JJ, James CR, Quinn JE, et al. BRCA1 transcriptionally regulates genes associated with the basal-like phenotype in breast cancer. Breast Cancer Res Treat 2010; 122: 721-731.
73.
Warmoes M, Lam SW, van der Groep P, et al. Secretome proteomics reveals candidate non-invasive biomarkers of BRCA1 deficiency in breast cancer. Oncotarget 2016; 7: 63537-63548.
74.
Roskoski R. The ErbB/HER family of protein-tyrosine kinases and cancer. Pharmacol Res 2014; 79: 34-74.
75.
Avraham R, Yarden Y. Feedback regulation of EGFR signalling: decision making by early and delayed loops. Nat Rev Mol Cell Biol 2011; 12: 104-117.
76.
Seshacharyulu P, Ponnusamy MP, Haridas D, et al. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets 2012; 16: 15-31.
77.
Gonzalez-Conchas GA, Rodriguez-Romo L, Hernandez-Barajas D, et al. Epidermal growth factor receptor overexpression and outcomes in early breast cancer: A systematic review and a meta-analysis. Cancer Treat Rev 2018; 62: 1-8.
78.
Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003; 100: 8418-8423.
79.
Lakhani SR, Reis-Filho JS, Fulford L, et al. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 2005; 11: 5175-5180.
80.
Foulkes WD, Stefansson IM, Chappuis PO, et al. Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 2003; 95: 1482-1485.
81.
Collins LC, Martyniak A, Kandel MJ, et al. Basal cytokeratin and epidermal growth factor receptor expression are not predictive of BRCA1 mutation status in women with triple-negative breast cancers. Am J Surg Pathol 2009; 33: 1093-1097.
82.
van der Groep P, Bouter A, van der Zanden R, et al. Distinction between hereditary and sporadic breast cancer on the basis of clinicopathological data. J Clin Pathol 2006; 59: 611-617.
83.
Arnes JB, Bégin LR, Stefansson I, et al. (2009) Expression of epidermal growth factor receptor in relation to BRCA1 status, basal-like markers and prognosis in breast cancer. J Clin Pathol 2009; 62: 139-146.
84.
Kang HH, Williams R, Leary J, et al. Evaluation of models to predict BRCA germline mutations. Br J Cancer 2006; 95: 914-920.
85.
Kang E, Kim S-W. The Korean hereditary breast cancer study: review and future perspectives. J Breast Cancer 2013; 16: 245-253.
86.
Biswas S, Atienza P, Chipman J, et al. A two-stage approach to genetic risk assessment in primary care. Breast Cancer Res Treat 2016; 155: 375-383.
87.
Spurdle AB, Couch FJ, Parsons MT, et al. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia. Breast Cancer Res 2014; 16: 3419.
88.
Vos S, Elias SG, van der Groep P, et al. Comprehensive proteomic profiling-derived immunohistochemistry-based prediction models for BRCA1 and BRCA2 germline mutation-related breast carcinomas. Am J Surg Pathol 2018; 42: 1262-1272.
89.
Hassanein M, Huiart L, Bourdon V, et al. Prediction of BRCA1 germ-line mutation status in patients with breast cancer using histoprognosis grade, MS110, Lys27H3, vimentin, and KI67. Pathobiology 2013; 80: 219-227.
90.
Miolo G, Canzonieri V, Giacomi C de, et al. Selecting for BRCA1 testing using a combination of homogeneous selection criteria and immunohistochemical characteristics of breast cancers. BMC Cancer 2009; 9: 360.
91.
Davies H, Glodzik D, Morganella S, et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat Med 2017; 23: 517-525.
92.
Hedenfalk I, Duggan D, Chen Y, et al. Gene-expression profiles in hereditary breast cancer. N Engl J Med 2001; 344: 539-548.
93.
Lips EH, Mulder L, Hannemann J, et al. Indicators of homologous recombination deficiency in breast cancer and association with response to neoadjuvant chemotherapy. Ann Oncol 2011; 22: 870-876.
94.
Branham MT, Campoy E, Laurito S, et al. Epigenetic regulation of ID4 in the determination of the BRCAness phenotype in breast cancer. Breast Cancer Res Treat 2016; 155: 13-23.
95.
Wessels LFA, van Welsem T, Hart AAM, et al. Molecular classification of breast carcinomas by comparative genomic hybridization: a specific somatic genetic profile for BRCA1 tumors. Cancer Res 2002; 62: 7110-7117.
96.
La Cruz J de, Andre F, Harrell RK, et al. Tissue-based predictors of germ-line BRCA1 mutations: Implications for triaging of genetic testing. Hum Pathol 2012; 43: 1932-1939.
97.
Mavaddat N, Rebbeck TR, Lakhani SR, et al. Incorporating tumour pathology information into breast cancer risk prediction algorithms. Breast Cancer Res 2010; 12: R28.
98.
Lee AJ, Cunningham AP, Kuchenbaecker KB, et al. BOADICEA breast cancer risk prediction model: updates to cancer incidences, tumour pathology and web interface. Br J Cancer 2014; 110: 535-545.
99.
Mavaddat N, Barrowdale D, Andrulis IL, et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomarkers Prev 2012; 21: 134-147.
100.
Antoniou AC, Hardy R, Walker L, et al. Predicting the likelihood of carrying a BRCA1 or BRCA2 mutation: validation of BOADICEA, BRCAPRO, IBIS, Myriad and the Manchester scoring system using data from UK genetics clinics. J Med Genet 2008; 45: 425-431.
101.
National Institute for Health and Care Excellence. Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer: Clinical guideline. 2013.
Share
RELATED ARTICLE
| eISSN: | 2084-9869 |
| ISSN: | 1233-9687 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
