Does Morphologic Apocrine Differentiation (AD) in Ductal or Lobular Breast Cancer Correlate with "Molecular Apocrine" Subset?
Denyo Zakhia, Nilesh S Gupta, Dhananjay A Chitale. Henry Ford Hospital, Detroit, MI
Background: Apocrine carcinoma (AC) is a rare morphologically defined subtype of invasive ductal carcinoma (IDC) which lacks estrogen (ER) and progesterone receptors (PgR) but expresses androgen receptors (AR). However, the histological criteria of AC are subjective and not reproducible. In addition, many pleomorphic lobular carcinomas (PLC) show apocrine features. Our aim was to define morphologic & immunohistochemical criteria for AD and explore whether there is a positive correlation of morphologic AD with AR expression.
Design: Cases of AC and PLC (invasive and in-situ) were identified from electronic records of a single institution from 1999 -2012. Additional cases were selected from review of ER- PgR- negative IDC from 1996 - 2009. AD was histologically defined as more than 90% of the tumor cells having large round nuclei, prominent nucleoli, eosinophilic, abundant, granular cytoplasm with sharp cell borders, and occasional apical snouting. Immunohistochemical stains were done using antibodies against ER, PgR, Her2, AR, MIB-1, GCDFP-15. ER, PgR, Her2 were scored using published ASCO/CAP guidelines. AR was semi-quantitatively scored using an H-score with score >10 considered a positive result. MIB-1 was scored as % positive tumor nuclei and were grouped into low (<25%) and high (>=25%).
Results: All cases were females. Of 21 AC cases, 13/21(62%) were invasive AC and 8/21(38%) apocrine DCIS (ADCIS). 20/21(95%) were positive for GCDFP-15 and AR with all cases showing >80% reactivity. All AC were ER and PR negative. 6/21(29%) showed HER2 overexpression, (3 ADCIS; 3 AC). 4/21(19%) showed high MIB-1 labelling, one of which was HER2+. Of 10 cases of PLC, there were 8/10 (80%) invasive PLC and 2/10(20%) pleomorphic lobular carcinoma in-situ (PLCIS). All PLC and PLCIS were negative for GCDFP-15, 9/10 (90%) showed >80% immunoreactivity to AR. 8/10 (80%) were ER+, 7/10(70%) PgR+, 4/10(40%) expressed high MIB-1 labelling. 2/10(20%) were HER2+, one of which was ER- PR-, high MIB-1.
Conclusions: We did not find morphologic differences in triple negative and Her2+ AC. AD, irrespective of the hormonal status or differentiation (ductal or lobular), significantly & consistently correlated with high AR positivity and relatively low MIB1 labeling. Thus AR+ /low MIB1 phenotype would help identify a relatively low risk group among aggressive triple negative breast cancers which may also identify cost effective therapeutic strategy for AR inhibitors in the management of patients with 'molecular apocrine' breast cancers. GCDFP-15 was strongly associated with AC but not PLC.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 2, Wednesday Afternoon