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01-04-2018 | Original Article

Immunohistochemical Analysis of the Expression of Breast Markers in Basal-like Breast Carcinomas Defined as Triple Negative Cancers Expressing Keratin 5

Authors: Tamás Zombori, Gábor Cserni

Published in: Pathology & Oncology Research | Issue 2/2018

Abstract

Estrogen and progesterone receptors are possible markers for suggesting a mammary origin of metastatic carcinoma, but are useless in cases of triple negative breast cancers (TNBC). Five other potential markers of breast origin were investigated on tissue microarrays in a series of TNBCs showing keratin 5 expression, consistent with a basal-like phenotype. GATA-3 staining was observed in 82 of 115 triple negative cases (71.3%) including 23 cases with >5% staining. Mammaglobin staining was detected in 30 cases (26.0%) including 12 with >5% staining. GCDFP-15 was seen in 23 cases (20.0%) including 9 with >5% staining. NY-BR-1 positivity was present in 7 cases (6.0%) including 3 patients with >5% staining. BCA-225 staining was observed in 74 cases (64.3%); however this latter marker lacks also specificity owing to the reported widespread staining in other malignancies. GATA-3, mammaglobin and GCDFP-15 coexpression was seen in one case (0.9%), whereas GATA-3 and mammaglobin or mammaglobin and GCDFP-15 coexpression was present in 2 and 2 cases (1.7%), respectively. Using at least 5% staining as cut-off, the expression of any of the last 4 markers was 34.7%. The expression of GATA-3, mammaglobin, GCDFP-15 and NY-BR-1 is lower in TNBC-s than in breast carcinomas in general, and this may be even lower in basal-like carcinomas. Although these markers are not fully specific, by using them, a subset of basal-like TNBC-s can be identified as of mammary origin. However, a substantial proportion will not show any staining with any of these markers.

DeSantis C, Ma J, Bryan L, Jemal A (2013) Breast cancer statistics, 2013. CA Cancer J Clin 64:52–62. doi:10.3322/caac.21203 CrossRefPubMed

Malvezzi M, Carioli G, Bertuccio P, Rosso T, Boffetta P, Levi F, La Vecchia C, Negri E (2016) European cancer mortality predictions for the year 2016 with focus on leukaemias. Ann Oncol 27:725–731. doi:10.1093/annonc/mdw022 CrossRefPubMed

Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752CrossRefPubMed

Nielsen TO, Perou CM (2015) CCR 20th anniversary commentary: the development of breast cancer molecular subtyping. Clin Cancer Res 21:1779–1781. doi:10.1158/1078-0432.CCR-14-2552 CrossRefPubMed

Hernandez BY, Green MD, Cassel KD, Pobutsky AM, Vu V, Wilkens LR (2010) Preview of Hawaii cancer facts and figures. Hawaii Med J 69:223–224PubMedPubMedCentral

Huo L, Gong Y, Guo M, Gilcrease MZ, Wu Y, Zhang H, Zhang J, Resetkova E, Hunt KK, Deavers MT (2015) GATA-binding protein 3 enhances the utility of gross cystic disease fluid protein-15 and mammaglobin a in triple-negative breast cancer by immunohistochemistry. Histopathology 67:245–254. doi:10.1111/his.12645 CrossRefPubMed

Deftereos G, Sanguino Ramirez AM, Silverman JF, Krishnamurti U (2015) GATA3 immunohistochemistry expression in histologic subtypes of primary breast carcinoma and metastatic breast carcinoma cytology. Am J Surg Pathol 39:1282–1289. doi:10.1097/PAS.0000000000000505 CrossRefPubMed

Chou J, Provot S, Werb Z (2010) GATA3 in development and cancer differentiation: cells GATA have it! J Cell Physiol 222:42–49. doi:10.1002/jcp.21943 CrossRefPubMedPubMedCentral

Esheba GE, Longacre TA, Atkins KA, Higgins JP (2009) Expression of the urothelial differentiation markers GATA3 and placental S100 (S100P) in female genital tract transitional cell proliferations. Am J Surg Pathol 33:347–353CrossRefPubMed

10.

Liu H, Shi J, Wilkerson ML, Lin F (2012) Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas. Am J Clin Pathol 138:57–64. doi:10.1309/AJCP5UAFMSA9ZQBZ CrossRefPubMed

11.

Ordonez NG (2013) Value of GATA3 immunostaining in tumor diagnosis: a review. Adv Anat Pathol 20:352–360. doi:10.1097/PAP.0b013e3182a28a68 CrossRefPubMed

12.

Miettinen M, McCue PA, Sarlomo-Rikala M, Rys J, Czapiewski P, Wazny K, Langfort R, Waloszczyk P, Biernat W, Lasota J, Wang Z (2014) GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol 38:13–22. doi:10.1097/PAS.0b013e3182a0218f CrossRefPubMedPubMedCentral

13.

Voduc D, Cheang M, Nielsen T (2008) GATA-3 expression in breast cancer has a strong association with estrogen receptor but lacks independent prognostic value. Cancer Epidemiol Biomark Prev 17:365–373. doi:10.1158/1055-9965.EPI-06-1090 CrossRef

14.

Hoch RV, Thompson DA, Baker RJ, Weigel RJ (1999) GATA-3 is expressed in association with estrogen receptor in breast cancer. Int J Cancer 84:122–128CrossRefPubMed

15.

Tominaga N, Naoi Y, Shimazu K, Nakayama T, Maruyama N, Shimomura A, Kim SJ, Tamaki Y, Noguchi S (2012) Clinicopathological analysis of GATA3-positive breast cancers with special reference to response to neoadjuvant chemotherapy. Ann Oncol 23:3051–3057. doi:10.1093/annonc/mds120 CrossRefPubMed

16.

Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F (2009) Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours. Breast Cancer Res 11:R40. doi:10.1186/bcr2327 CrossRefPubMedPubMedCentral

17.

Parikh P, Palazzo JP, Rose LJ, Daskalakis C, Weigel RJ (2005) GATA-3 expression as a predictor of hormone response in breast cancer. J Am Coll Surg 200:705–710CrossRefPubMed

18.

Mehra R, Varambally S, Ding L, Shen R, Sabel MS, Ghosh D, Chinnaiyan AM, Kleer CG (2005) Identification of GATA3 as a breast cancer prognostic marker by global gene expression meta-analysis. Cancer Res 65:11259–11264CrossRefPubMed

19.

Cimino-Mathews A, Subhawong AP, Illei PB, Sharma R, Halushka MK, Vang R, Fetting JH, Park BH, Argani P (2013) GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas. Hum Pathol 44:1341–1349. doi:10.1016/j.humpath.2012.11.003 CrossRefPubMedPubMedCentral

20.

Ciocca V, Daskalakis C, Ciocca RM, Ruiz-Orrico A, Palazzo JP (2009) The significance of GATA3 expression in breast cancer: a 10-year follow-up study. Hum Pathol 40:489–495. doi:10.1016/j.humpath.2008.09.010 CrossRefPubMed

21.

Jacquemier J, Charafe-Jauffret E, Monville F, Esterni B, Extra JM, Houvenaeghel G, Xerri L, Bertucci F, Birnbaum D (2009) Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer. Breast Cancer Res 11:R23. doi:10.1186/bcr2249 CrossRefPubMedPubMedCentral

22.

Demir H, Turna H, Can G, Ilvan S (2010) Clinicopathologic and prognostic evaluation of invasive breast carcinoma molecular subtypes and GATA3 expression. J Buon 15:774–782PubMed

23.

Watson MA, Fleming TP (1996) Mammaglobin, a mammary-specific member of the uteroglobin gene family, is overexpressed in human breast cancer. Cancer Res 56:860–865PubMed

24.

Watson MA, Darrow C, Zimonjic DB, Popescu NC, Fleming TP (1998) Structure and transcriptional regulation of the human mammaglobin gene, a breast cancer associated member of the uteroglobin gene family localized to chromosome 11q13. Oncogene 16:817–824CrossRefPubMed

25.

Han JH, Kang Y, Shin HC, Kim HS, Kang YM, Kim YB, Oh SY (2003) Mammaglobin expression in lymph nodes is an important marker of metastatic breast carcinoma. Arch Pathol Lab Med 127:1330–1334PubMed

26.

Bhargava R, Beriwal S, Dabbs DJ (2007) Mammaglobin vs GCDFP-15: an immunohistologic validation survey for sensitivity and specificity. Am J Clin Pathol 127:103–113CrossRefPubMed

27.

Zafrakas M, Petschke B, Donner A, Fritzsche F, Kristiansen G, Knüchel R, Dahl E (2006) Expression analysis of mammaglobin a (SCGB2A2) and lipophilin B (SCGB1D2) in more than 300 human tumors and matching normal tissues reveals their co-expression in gynecologic malignancies. BMC Cancer 6:88CrossRefPubMedPubMedCentral

28.

Sasaki E, Tsunoda N, Hatanaka Y, Mori N, Iwata H, Yatabe Y (2007) Breast-specific expression of MGB1/mammaglobin: an examination of 480 tumors from various organs and clinicopathological analysis of MGB1-positive breast cancers. Mod Pathol 20:208–214CrossRefPubMed

29.

Wang Z, Spaulding B, Sienko A, Liang Y, Li H, Nielsen G, Yub Gong G, Ro JY, Jim Zhai Q (2009) Mammaglobin, a valuable diagnostic marker for metastatic breast carcinoma. Int J Clin Exp Pathol 2:384–389PubMed

30.

Onuma K, Dabbs DJ, Bhargava R (2008) Mammaglobin expression in the female genital tract: immunohistochemical analysis in benign and neoplastic endocervix and endometrium. Int J Gynecol Pathol 27:418–425. doi:10.1097/PGP.0b013e31815d05ec CrossRefPubMed

31.

Al-Joudi FS, Kaid FA, Ishak I, Mohamed N, Osman K, Alias IZ (2011) Expression of human mammaglobin and clinicopathologic correlations in breast cancer: the findings in Malaysia. Indian J Pathol Microbiol 54:284–289. doi:10.4103/0377-4929.81596 CrossRefPubMed

32.

Lewis GH, Subhawong AP, Nassar H, Vang R, Illei PB, Park BH, Argani P (2011) Relationship between molecular subtype of invasive breast carcinoma and expression of gross cystic disease fluid protein 15 and mammaglobin. Am J Clin Pathol 135:587–591. doi:10.1309/AJCPMFR6OA8ICHNH CrossRefPubMedPubMedCentral

33.

Fritzsche FR, Thomas A, Winzer KJ, Beyer B, Dankof A, Bellach J, Dahl E, Dietel M, Kristiansen G (2007) Co-expression and prognostic value of gross cystic disease fluid protein 15 and mammaglobin in primary breast cancer. Histol Histopathol 22:1221–1230PubMed

34.

Haagensen DE Jr, Mazoujian G, Holder WD Jr, Kister SJ, Wells SA Jr (1977) Evaluation of a breast cyst fluid protein detectable in the plasma of breast carcinoma patients. Ann Surg 185:279–285CrossRefPubMedPubMedCentral

35.

Wick MR, Lillemoe TJ, Copland GT, Swanson PE, Manivel JC, Kiang DT (1989) Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin. Hum Pathol 20:281–287CrossRefPubMed

36.

Park SY, Kim BH, Kim JH, Lee S, Kang GH (2007) Panels of immunohistochemical markers help determine primary sites of metastatic adenocarcinoma. Arch Pathol Lab Med 131:1561–1567PubMed

37.

Jäger D, Stockert E, Güre AO, Scanlan MJ, Karbach J, Jäger E, Knuth A, Old LJ, Chen YT (2001) Identification of a tissue-specific putative transcription factor in breast tissue by serological screening of a breast cancer library. Cancer Res 61:2055–2061PubMed

38.

Jäger D, Filonenko V, Gout I, Frosina D, Eastlake-Wade S, Castelli S, Varga Z, Moch H, Chen YT, Busam KJ, Seil I, Old LJ, Nissan A, Frei C, Gure AO, Knuth A, Jungbluth AA (2007) NY-BR-1 is a differentiation antigen of the mammary gland. Appl Immunohistochem Mol Morphol 15:77–83CrossRefPubMed

39.

Giger OT, Lacoste E, Honegger C, Padberg B, Moch H, Varga Z (2007) Expression of the breast differentiation antigen NY-BR-1 in a phyllodes tumor of the vulva. Virchows Arch 450:471–474CrossRefPubMed

40.

Varga Z, Theurillat JP, Filonenko V, Sasse B, Odermatt B, Jungbluth AA, Chen YT, Old LJ, Knuth A, Jäger D, Moch H (2006) Preferential nuclear and cytoplasmic NY-BR-1 protein expression in primary breast cancer and lymph node metastases. Clin Cancer Res 12:2745–2751CrossRefPubMed

41.

Theurillat JP, Zürrer-Härdi U, Varga Z, Storz M, Probst-Hensch NM, Seifert B, Fehr MK, Fink D, Ferrone S, Pestalozzi B, Jungbluth AA, Chen YT, Jäger D, Knuth A, Moch H (2007) NY-BR-1 protein expression in breast carcinoma: a mammary gland differentiation antigen as target for cancer immunotherapy. Cancer Immunol Immunother 56:1723–1731CrossRefPubMed

42.

Seil I, Frei C, Sültmann H, Knauer SK, Engels K, Jäger E, Zatloukal K, Pfreundschuh M, Knuth A, Tseng-Chen Y, Jungbluth AA, Stauber RH, Jäger D (2007) The differentiation antigen NY-BR-1 is a potential target for antibody-based therapies in breast cancer. Int J Cancer 120:2635–2642CrossRefPubMed

43.

Woodard AH, Yu J, Dabbs DJ, Beriwal S, Florea AV, Elishaev E, Davison JM, Krasinskas AM, Bhargava R (2011) NY-BR-1 and PAX8 immunoreactivity in breast, gynecologic tract, and other CK7+ carcinomas: potential use for determining site of origin. Am J Clin Pathol 136:428–435. doi:10.1309/AJCPUFNMEZ3MK1BK CrossRefPubMed

44.

Balafoutas D, zur Hausen A, Mayer S, Hirschfeld M, Jaeger M, Denschlag D, Gitsch G, Jungbluth A, Stickeler E (2013) Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications. BMC Cancer 13:271. doi:10.1186/1471-2407-13-271 CrossRefPubMedPubMedCentral

45.

Liu H (2014) Application of immunohistochemistry in breast pathology: a review and update. Arch Pathol Lab Med 138:1629–1642. doi:10.5858/arpa.2014-0094-RA CrossRefPubMed

46.

Mesa-Tejada R, Palakodety RB, Leon JA, Khatcherian AO, Greaton CJ (1988) Immunocytochemical distribution of a breast carcinoma associated glycoprotein identified by monoclonal antibodies. Am J Pathol 130:305–314PubMedPubMedCentral

47.

Loy TS, Chapman RK, Diaz-Arias AA, Bulatao IS, Bickel JT (1991) Distribution of BCA-225 in adenocarcinomas. An immunohistochemical study of 446 cases. Am J Clin Pathol 96:326–329CrossRefPubMed

48.

Abramson VG, Lehmann BD, Ballinger TJ, Pietenpol JA (2015) Subtyping of triple-negative breast cancer: implications for therapy. Cancer 121:8–16. doi:10.1002/cncr.28914 CrossRefPubMed

49.

Vranic S, Schmitt F, Sapino A, Costa JL, Reddy S, Castro M, Gatalica Z (2013) Apocrine carcinoma of the breast: a comprehensive review. Histol Histopathol 28:1393–1409. doi:10.14670/HH-28.1393 PubMed

50.

Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, van de Rijn M, Perou CM (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10:5367–5374CrossRefPubMed

51.

Sasahara M, Matsui A, Ichimura Y, Hirakata Y, Murata Y, Marui E (2014) Overexpression of androgen receptor and forkhead-box A1 protein in apocrine breast carcinoma. Anticancer Res 34:1261–1267PubMed

52.

Kővári B, Rusz O, Schally AV, Kahán Z, Cserni G (2014) Differential immunostaining of various types of breast carcinomas for growth hormone-releasing hormone (GHRH) receptor - apocrine epithelium and carcinomas emerging as uniformly positive. APMIS 122:824–831. doi:10.1111/apm.12224 CrossRefPubMed

53.

Ordonez NG, Sahin AA (2014) Diagnostic utility of immunohistochemistry in distinguishing between epithelioid pleural mesotheliomas and breast carcinomas: a comparative study. Hum Pathol 45:1529–1540. doi:10.1016/j.humpath.2014.03.006 CrossRefPubMed

54.

Krings G, Nystrom M, Mehdi I, Vohra P, Chen YY (2014) Diagnostic utility and sensitivities of GATA3 antibodies in triple-negative breast cancer. Hum Pathol 45:2225–2232. doi:10.1016/j.humpath.2014.06.022 CrossRefPubMed

55.

Braxton DR, Cohen C, Siddiqui MT (2015) Utility of GATA3 immunohistochemistry for diagnosis of metastatic breast carcinoma in cytology specimens. Diagn Cytopathol 43:271–277. doi:10.1002/dc.23206 CrossRefPubMed

56.

Lew M, Pang JC, Jing X, Fields KL, Roh MH (2015) Young investigator challenge: the utility of GATA3 immunohistochemistry in the evaluation of metastatic breast carcinomas in malignant effusions. Cancer Cytopathol 123:576–581. doi:10.1002/cncy.21574 CrossRefPubMed

57.

Rakhshani N, Daryakar A (2014) Are mammaglobin and GCDFP-15 sensitive markers for diagnosis of metastatic basal-like triple negative breast carcinomas? Turk Patoloji Derg 30:18–22. doi:10.5146/tjpath.2013.01202 PubMed

58.

Darb-Esfahani S, von Minckwitz G, Denkert C, Ataseven B, Högel B, Mehta K, Kaltenecker G, Rüdiger T, Pfitzner B, Kittel K, Fiedler B, Baumann K, Moll R, Dietel M, Eidtmann H, Thomssen C, Loibl S (2014) Gross cystic disease fluid protein 15 (GCDFP-15) expression in breast cancer subtypes. BMC Cancer 14:546. doi:10.1186/1471-2407-14-546 CrossRefPubMedPubMedCentral

59.

Pala EE, Bayol Ü, Cumurcu S, Keskın E (2012) Immunohistochemical characteristics of triple negative/basal-like breast cancer. Turk Patoloji Derg 28:238–244. doi:10.5146/tjpath.2012.01130 PubMed

60.

Clark BZ, Beriwal S, Dabbs DJ, Bhargava R (2014) Semiquantitative GATA-3 immunoreactivity in breast, bladder, gynecologic tract, and other cytokeratin 7-positive carcinomas. Am J Clin Pathol 142:64–71. doi:10.1309/AJCP8H2VBDSCIOBF CrossRefPubMed

61.

Gloyeske NC1, Woodard AH, Elishaev E, Yu J, Clark BZ, Dabbs DJ, Bhargava R (2015) Immunohistochemical profile of breast cancer with respect to estrogen receptor and HER2 status. Appl Immunohistochem Mol Morphol 23:202–208. doi:10.1097/PAI.0000000000000076 CrossRefPubMed

Title: Immunohistochemical Analysis of the Expression of Breast Markers in Basal-like Breast Carcinomas Defined as Triple Negative Cancers Expressing Keratin 5
Authors: Tamás Zombori
Gábor Cserni
Publication date: 01-04-2018
Publisher: Springer Netherlands
Published in: Pathology & Oncology Research / Issue 2/2018
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-017-0246-y

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