Morphologic and molecular evolutionary pathways of low nuclear grade invasive breast cancers and their putative precursor lesions: Further evidence to support the concept of low nuclear grade breast neoplasia family

被引:158
作者
Abdel-Fatah, Tarek M. A. [1 ,2 ]
Powe, Desmond G. [1 ,2 ]
Hodi, Zsolt [1 ,2 ]
Reis-Filho, Jorge S. [3 ]
Lee, Andrew H. S. [1 ,2 ]
Ellis, Ian O. [1 ,2 ]
机构
[1] Univ Nottingham, Div Pathol, Sch Mol Med Sci, Nottingham NG7 2RD, England
[2] Univ Nottingham, Nottingham Univ Hosp Trust, Nottingham NG7 2RD, England
[3] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England
关键词
TDLUs; columnar cell lesions; flat epithelial atypia; ADH; DCIS; luminal "A" subclass of breast carcinoma; tissue microarray; immunoprofile of precursors lesions and their coexisting breast carcinoma;
D O I
10.1097/PAS.0b013e318161d1a5
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
We have previously provided evidence showing an association between some precursor lesions with low nuclear grade breast carcinomas (LNGBCs). In this study, further immunophenotypic support to our proposed route of pathogenesis of LNGBC and their precursor lesions was provided. Precursor lesions including columnar cell lesions, atypical ductal hyperplasia, ductal carcinoma in situ, usual epithelial hyperplasia, and lobular neoplasia were compared with matching "morphologically normal" terminal lobular duct units and matching invasive carcinoma. The epithelia] cells in the putative precursor flat epithelia] atypia, atypical ductal hyperplasia, lobular neoplasia, ductal carcinoma in situ lesions, and their coexisting LNGBC were negative for basal and myoepithelial markers, but Positive for CK19/18/8, estrogen receptor (ER)-alpha, Bcl-2, and cyclin D1. The ER-alpha/ER-beta expression ratio increased during carcinogenesis, as did expression of cyclin D1 and Bcl-2. p53 immunopositivity was found 3% in LNGBC versus 43% in high nuclear grade breast carcinoma (HNGBC), whereas ataxia telangiectasia mutated expression was absent or reduced ill 22% of LNGBC versus 53% of HNGBC cases. In summary, our findings support the concept that flat epithelial atypia is the earliest morphologically identifiable nonobligate precursor lesion of LNGBC. These may represent a family of precursor, in situ and invasive neoplastic lesions belonging to the luminal "A" subclass of breast cancer. The balance between ER-g, and ER-beta expression may be important in driving cyclin D-1 and Bcl-2 expression. Ataxia telangiectasia mutated may be one of the alternative regulatory mechanisms to TP53 mutation or dysfunction in low-grade and high-grade breast carcinoma. Our findings Support the concept that progression of LNGBC to HNGBC (basal-like or HER2+) phenotype is an unlikely biologic phenomenon.
引用
收藏
页码:513 / 523
页数:11
相关论文
共 54 条
[1]   High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses [J].
Abd El-Rehim, DM ;
Ball, G ;
Pinder, SE ;
Rakha, E ;
Paish, C ;
Robertson, JFR ;
Macmillan, D ;
Blamey, RW ;
Ellis, IO .
INTERNATIONAL JOURNAL OF CANCER, 2005, 116 (03) :340-350
[2]   High frequency of coexistence of columnar cell lesions, lobular neoplasia, and low grade ductal carcinoma in situ with invasive tubular carcinoma and invasive lobular carcinoma [J].
Abdel-Fatah, Tarek M. A. ;
Powe, Desmond G. ;
Hodi, Zsolt ;
Lee, Andrew H. S. ;
Reis-Filho, Jorge S. ;
Ellis, Ian O. .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2007, 31 (03) :417-426
[3]  
Alle KM, 1998, CLIN CANCER RES, V4, P847
[4]  
Allred DC, 1998, MODERN PATHOL, V11, P155
[5]  
Anbazhagan R, 1998, J PATHOL, V184, P197, DOI 10.1002/(SICI)1096-9896(199802)184:2&lt
[6]  
197::AID-PATH992&gt
[7]  
3.0.CO
[8]  
2-J
[9]   Premalignant and in situ breast disease: Biology and clinical implications [J].
Arpino, G ;
Laucirica, R ;
Elledge, RM .
ANNALS OF INTERNAL MEDICINE, 2005, 143 (06) :446-457
[10]   Accumulation of chromosomal imbalances from intraductal proliferative lesions to adjacent in situ and invasive ductal breast cancer [J].
Aubele, MM ;
Cummings, MC ;
Mattis, AE ;
Zitzelsberger, HF ;
Walch, AK ;
Kremer, M ;
Höfler, H ;
Werner, M .
DIAGNOSTIC MOLECULAR PATHOLOGY, 2000, 9 (01) :14-19