The study was performed to assess the status of immunohistochemical markers in primary and metastatic breast cancer and to determine the organ-specific characteristics of metastatic breast cancer.
Methods
Samples from 13 cases of paired primary and metastatic breast cancer and 34 cases of metastatic breast cancer were included.
Results
In the analysis of 13 cases of paired primary and metastatic breast cancer, estrogen receptor and progesterone receptor loss were noted in 1 (7.7%) case each. Androgen receptor loss and gain was noted in 2 (15.4%) cases, respectively. HER-2 showed 100% concordance with primary and metastatic tumors. C-kit was demonstrated in only 2 (15.4%) cases of metastatic breast cancer. In the analysis of 34 cases of metastatic breast cancer, when classified into triple-negative type (ER-, PR-, and HER-2-), HER-2+ type, and ER+ or PR+/HER-2- type according to immunohistochemical stain results, HER-2 type (66.7%) in brain metastasis and ER+ or PR+/HER-2- type (75.0%) in liver metastasis were predominant. Bone metastasis was composed of triple negative type (44.4%) and ER+ or PR+/HER-2- type (55.6%), and lung metastasis showed all of three subtypes in similar proportions.
Conclusions
Metastatic breast cancer shows different immunohistochemical phenotypes according to metastatic site (P = 0.048).
WeilR.J., PalmieriD.C., BronderJ.L., StarkA.M., SteegP.S.: Breast cancer metastasis to the central nervous system. Am J Pathol, 167: 913–920, 2005.
2.
NicolsonG.L.: Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev, 7: 143–188, 1988.
3.
WoodhouseE.C., ChuaquiR.F., LiottaL.A.: General mechanisms of metastasis. Cancer, 80: 1529–1537, 1997.
4.
PagetS.: The distribution of secondary growths in cancer of the breast. Lancet, 1: 571–572, 1889.
5.
GancbergD., Di LeoA., CardosoF., RouasG., PedrocchiM., PaesmansM., VerhestA., Bernard-MartyC., PiccartM.J., LarsimontD.: Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol, 13: 1036–1043, 2002.
6.
FidlerI.J.: Review: biologic heterogeneity of cancer metastases. Breast Cancer Res Treat, 9: 17–26, 1987.
7.
AbaliH., CelikI.: High incidence of central nervous system involvementin patients with breast cancer treated with epirubicin and docetaxel. Am J Clin Oncol, 25: 632–633, 2002.
8.
ColleoniM., O'NeillA., GoldhirschA., GelberR.D., BonettiM., ThurlimannB., PriceK.N., Castiglione-GertschM., CoatesA.S., LindtnerJ., CollinsJ., SennH.J., CavalliF., ForbesJ., GudgeonA., SimonciniE., Cortes-FunesH., VeronesiA., FeyM., RudenstamC.M.: Identifying breast cancer patients at high risk for bone metastases. J Clin Oncol, 18: 3925–3935, 2000.
9.
EvansA.J., JamesJ.J., CornfordE.J., ChanS.Y., BurrellH.C., PinderS.E., GutteridgeE., RobertsonJ.F., HornbuckleJ., CheungK.L.: Brain metastases from breast cancer: identification of a high-risk group. Clin Oncol (R Coll Radiol), 16: 345–349, 2004.
10.
GaedckeJ., TraubF., MildeS., WilkensL., StanA., OstertagH., ChristgenM., von WasielewskiR., KreipeH.H.: Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer. Mod Pathol, 20: 864–870, 2007.
11.
HicksD.G., ShortS.M., PrescottN.L., TarrS.M., ColemanK.A., YoderB.J., CroweJ.P., ChoueiriT.K., DawsonA.E., BuddG.T., TubbsR.R., CaseyG., WeilR.J.: Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin CK5/6, and overexpress HER2 or EGFR. Am J Surg Pathol, 30: 1097–1104, 2006.
12.
LorinczT., TothJ., BadalianG., TimarJ., SzendroiM.: HER-2/neu genotype of breast cancer may change in bone metastasis. Pathol Oncol Res, 12: 149–152, 2006.
13.
AllredD.C., ClarkG.M., TandonA.K., MolinaR., TormeyD.C., OsborneC.K., GilchristK.W., MansourE.G., AbeloffM., EudeyL.: HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol, 10: 599–605, 1992.
14.
WolffA.C., HammondM.E., SchwartzJ.N., HagertyK.L., AllredD.C., CoteR.J., DowsettM., FitzgibbonsP.L., HannaW.M., LangerA., McShaneL.M., PaikS., PegramM.D., PerezE.A., PressM.F., RhodesA., SturgeonC., TaubeS.E., TubbsR., VanceG.H., van de VijverM., WheelerT.M., HayesD.F.: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol, 25: 118–145, 2007.
15.
Brunn RasmussenB., KambyC.: Immunohistochemical detection of estrogen receptors in paraffin sections from primary and metastatic breast cancer. Pathol Res Pract, 185: 856–859, 1989.
16.
Gomez-FernandezC., DaneshbodY., NassiriM., MilikowskiC., AlvarezC., NadjiM.: Immunohistochemically determined estrogen receptor phenotype remains stable in recurrent and metastatic breast cancer. Am J Clin Pathol, 130: 879–882, 2008.
17.
KuukasjarviT., KononenJ., HelinH., HolliK., IsolaJ.: Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy. J Clin Oncol, 14: 2584–2589, 1996.
18.
AgoffS.N., SwansonP.E., LindenH., HawesS.E., LawtonT.J.: Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol, 120: 725–731, 2003.
19.
HanleyK., WangJ., BourneP., YangQ., GaoA.C., LymanG., TangP.: Lack of expression of androgen receptor may play a critical role in transformation from in situ to invasive basal subtype of high-grade ductal carcinoma of the breast. Hum Pathol, 39: 386–392, 2008.
20.
SoreideJ.A., LeaO.A., VarhaugJ.E., SkarsteinA., KvinnslandS.: Androgen receptors in operable breast cancer: relation to other steroid hormone receptors, correlations to prognostic factors and predictive value for effect of adjuvant tamoxifen treatment. Eur J Surg Oncol, 18: 112–118, 1992.
21.
TannerM., JarvinenP., IsolaJ.: Amplification of HER-2/neu and topoisomerase II alpha in primary and metastatic breast cancer. Cancer Res, 61: 5345–5348, 2001.
22.
Vincent-SalomonA., JouveM., GeninP., FreneauxP., Sigal-ZafraniB., CalyM., BeuzebocP., PouillartP., Sastre-GarauX.: HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic process. Cancer, 94: 2169–2173, 2002.
23.
ZidanJ., DashkovskyI., StayermanC., BasherW., CozacovC., HadaryA.: Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer, 93: 552–556, 2005.
24.
DentR., HannaW.M., TrudeauM., RawlinsonE., SunP., NarodS.A.: Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat, 115: 423–428, 2009.
25.
LivasyC.A., KaracaG., NandaR., TretiakovaM.S., OlopadeO.I., MooreD.T., PerouC.M.: Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol, 19: 264–271, 2006.
26.
YaredM.A., MiddletonL.P., MericF., CristofanilliM., SahinA.A.: Expression of c-kit proto-oncogene product in breast tissue. Breast J, 10: 323–327, 2004.
27.
NataliP.G., NicotraM.R., SuresI., MottoleseM., BottiC., UllrichA.: Breast cancer is associated with loss of the c-kit oncogene product. Int J Cancer, 52: 713–717, 1992.
28.
MillerK.D., WeathersT., HaneyL.G., TimmermanR., DicklerM., ShenJ., SledgeG.W.Jr.: Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival. Ann Oncol, 14: 1072–1077, 2003.
29.
HasebeT., ImotoS., YokoseT., IshiiG., IwasakiM., WadaN.: Histopathologic factors significantly associated with initial organ-specific metastasis by invasive ductal carcinoma of the breast: a prospective study. Hum Pathol, 39: 681–693, 2008.
30.
WeiB., WangJ., BourneP., YangQ., HicksD., BuH., TangP.: Bone metastasis is strongly associated with estrogen receptor-positive/progesterone receptor-negative breast carcinomas. Hum Pathol, 39: 1809–1815, 2008.
31.
GaoD., DuJ., CongL., LiuQ.: Risk factors for initial lung metastasis from breast invasive ductal carcinoma in stages I-III of operable patients. Jpn J Clin Oncol, 39: 97–104, 2008.
32.
Kuenen-BoumeesterV., Van der KwastT.H., ClaassenC.C., LookM.P., LiemG.S., KlijnJ.G., Henzen-LogmansS.C.: The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters. Eur J Cancer, 32A: 1560–1565, 1996.
33.
AgoffS.N., SwansonP.E., LindenH., HawesS.E., LawtonT.J.: Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol, 120: 725–731, 2003.
34.
IsolaJ.J.: Immunohistochemical demonstration of androgen receptor in breast cancer and its relationship to other prognostic factors. J Pathol, 170: 31–35, 1993.
35.
MoinfarF., OkcuM., TsybrovskyyO., RegitnigP., LaxS.F., WeyboraW., RatschekM., TavassoliF.A., DenkH.: Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new therapeutic strategies. Cancer, 98: 703–711, 2003.
36.
BiecheI., ParfaitB., TozluS., LidereauR., VidaudM.: Quantitation of androgen receptor gene expression in sporadic breast tumors by real-time RT-PCR: evidence that MYC is an AR-regulated gene. Carcinogenesis, 22: 1521–1526, 2001.
