Androgen receptor is frequently expressed in HER2-positive, ER/PR-negative breast cancers.
The estrogen receptor (ER)/progesterone receptor (PR)-negative breast carcinomas (BCs) encompass three molecular subtypes: one with human epidermal growth factor receptor 2 (HER) overexpression, one normal like, and the triple negative. The androgen receptor (AR) is expressed in 70-90% of invasive BCs. The aim of our study is to detect the expression of AR in a series of ER/PR-negative BCs to ascertain if there is clinical significance in relation to BC molecular subtypes. A immunohistochemical study for all receptors and cytokeratin expression was performed in 232 cases of ER/PR-negative BCs. According to cytokeratin expression, BCs were classified into two groups: luminal-type BCs (44.2%) and basal-like-type BCs (55.8%). According to the expression of HER2, 59.3% were triple-negative BCs (when ER, PR, and HER2 were negative) and 40.7% were HER2-positive BCs. AR expression was observed in 128 tumors (56.6%). One hundred and ten cases (48.8%) had >10% and 18 (7.8%) had <10% of positively stained cells. AR immunoreactivity was found in 31.2% basal-like BCs, while in the luminal group 71.1% of cases were positive, showing highly significant correlation (p < 10⁻⁸). Regarding HER2 status, 76.7% of HER2-positive BC cases were AR positive compared with only 30.4% of triple-negative BC types, showing a strong statistically significant correlation. In conclusion, we show that AR is frequently expressed in ER/PR-negative BCs and that expression of HER2 and AR is highly correlated (p < 0.005). Our results point out the role of AR and HER2 in the pathogenesis of BCs and suggest the potential role of AR in clinical management of ER/PR-negative BCs.
Micello
Donata
D
Department of Anatomic Pathology, Multimedica IRCCS, Milan, Italy.
Marando
Alessandro
A
Sahnane
Nora
N
Riva
Cristina
C
Capella
Carlo
C
Sessa
Fausto
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011944:Receptors, Androgen / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*
D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
J Clin Invest. 1999 Jun;103(12):1617-8
10377165
Clin Cancer Res. 2004 Aug 15;10(16):5367-74
15328174
Histopathology. 2007 Mar;50(4):434-8
17448018
Am J Surg. 1989 Jun;157(6):577-80; discussion 581
2499206
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5458-63
10318905
Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4185-91
16857790
Future Oncol. 2008 Feb;4(1):15-21
18240997
Br J Cancer. 1996 Oct;74(8):1175-80
8883401
Gan To Kagaku Ryoho. 2004 Dec;31(13):2151-3
15628761
Oncogene. 2005 Jul 7;24(29):4660-71
15897907
Neoplasia. 2008 Jun;10(6):542-8
18516291
J Pathol. 2006 Mar;208(4):495-506
16429394
Eur J Cancer. 1996 Aug;32A(9):1560-5
8911118
J Pathol. 1993 May;170(1):31-5
8100853
Virchows Arch. 2006 Jul;449(1):24-30
16628414
Mod Pathol. 2005 Jan;18(1):26-35
15332092
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8418-23
12829800
Int J Cancer. 2005 Sep 1;116(3):340-50
15818618
Cancer Res. 1989 Dec 15;49(24 Pt 1):7162-7
2582456
Cancer. 2003 Aug 15;98(4):703-11
12910513
Breast Cancer Res Treat. 1995 Sep;35(3):283-91
7579499
Oncogene. 2000 May 18;19(22):2664-77
10851066
Cancer Cell. 2004 Nov;6(5):517-27
15542435
Mod Pathol. 2010 Feb;23(2):205-12
19898421
Br J Cancer. 2001 Aug 3;85(3):422-7
11487275
Eur J Surg Oncol. 1992 Apr;18(2):112-8
1582503
Folia Histochem Cytobiol. 2006;44(3):165-72
16977795
Mod Pathol. 2000 Feb;13(2):119-22
10697267
Arch Pathol Lab Med. 2002 Mar;126(3):325-30
11860308
Nature. 2000 Aug 17;406(6797):747-52
10963602
Br J Cancer. 1994 Sep;70(3):434-9
7915911
Mol Cancer. 2006 Jun 19;5:24
16784538
Mod Pathol. 2005 Oct;18(10):1321-8
15990899
Cancer Cell. 2006 Oct;10(4):309-19
17045208
Breast. 2004 Aug;13(4):321-4
15325667
Clin Breast Cancer. 2004 Jun;5(2):136-41
15245618
Mod Pathol. 2005 Oct;18(10):1283-8
15920545
Am J Clin Pathol. 1999 Jul;112(1 Suppl 1):S53-67
10396301
Cancer. 1984 Dec 1;54(11):2436-40
6498736
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74
11553815
J Cancer Res Clin Oncol. 2002 Feb;128(2):85-90
11862478
Carcinogenesis. 2001 Sep;22(9):1521-6
11532875
Histopathology. 1991 Nov;19(5):403-10
1757079
Am J Clin Pathol. 2003 Nov;120(5):725-31
14608899
Int J Cancer. 1992 Oct 21;52(4):581-4
1399140
Cancer Res. 2005 Apr 15;65(8):3404-9
15833875
Cancer. 2007 Jan 1;109(1):25-32
17146782
J Histochem Cytochem. 1993 May;41(5):671-8
8468448
Ann Oncol. 2010 Mar;21(3):488-492
19887463
Virchows Arch. 2005 Oct;447(4):695-700
16075292
Oncogene. 2006 Jun 29;25(28):3994-4008
16491124
J Surg Oncol. 2007 May 1;95(6):437-9
17192921
Mod Pathol. 1998 Feb;11(2):155-68
9504686