Expression of neuroendocrine markers in different molecular subtypes of breast carcinoma.
BACKGROUND
Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic) luminal A subtype.


METHODS
We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin).


RESULTS
We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A). In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior.


CONCLUSIONS
We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies.
Institute of Pathology, University Hospital, Krankenhausstr 8-10, Erlangen 91054, Germany.
David L
DL
Wachter
Institute of Pathology, University Hospital, Krankenhausstr 8-10, Erlangen 91054, Germany.
Arndt
A
Hartmann
Department of Gynecology and Obstetrics, University Hospital, Universitätsstr 21, Erlangen 91054, Germany.
Matthias W
MW
Beckmann
Department of Gynecology and Obstetrics, University Hospital, Universitätsstr 21, Erlangen 91054, Germany.
Peter A
PA
Fasching
Department of Gynecology and Obstetrics, University Hospital, Universitätsstr 21, Erlangen 91054, Germany.
Alexander
A
Hein
Department of Gynecology and Obstetrics, University Hospital, Universitätsstr 21, Erlangen 91054, Germany.
Christian M
CM
Bayer
Institute of Pathology, University Hospital, Krankenhausstr 8-10, Erlangen 91054, Germany.
Abbas
A
Agaimy
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D053379:Chromogranin A / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D055099:Neuroendocrine Cells / Q000378:metabolism; D011379:Prognosis; D016708:Synaptophysin / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D053379:Chromogranin A; D016708:Synaptophysin