Detection of mammaglobin mRNA in peripheral blood is associated with high grade breast cancer: interim results of a prospective cohort study.
BACKGROUND
We sought to examine the detection rate of cancer cells in peripheral blood (PBL) and in bone marrow (BM) using an established 7-gene marker panel and evaluated whether there were any definable associations of any individual gene with traditional predictors of prognosis.


METHODS
Patients with T1-T3 primary breast cancer were enrolled into a prospective, multi-institutional cohort study. In this interim analysis 215 PBL and 177 BM samples were analyzed by multimarker, real-time RT-PCR analysis designed to detect circulating and disseminated breast cancer cells.


RESULTS
At a threshold of three standard deviations from the mean expression level of normal controls, 63% (136/215) of PBL and 11% (19/177) of BM samples were positive for at least one cancer-associated marker. Marker positivity in PBL demonstrated a statistically significant association with grade II-III (vs. grade I; p = 0.0083). Overexpression of the mammaglobin (mam) gene alone had a statistically significant association with high tumor grade (p = 0.0315), and showed a trend towards ER-negative tumors and a high risk category. There was no association between marker positivity in PBL and the pathologic (H&E) and/or molecular (RT-PCR) status of the axillary lymph nodes (ALN).


CONCLUSIONS
This study suggests that molecular detection of circulating cancer cells in PBL detected by RT-PCR is associated with high tumor grade and specifically that overexpression of the mam gene in PBL may be a poor prognostic indicator. There was no statistically significant association between overexpression of cancer-associated genes in PBL and ALN status, supporting the concept of two potentially separate metastatic pathways.
Mikhitarian
Kaidi
K
Department of Surgery, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425, USA. mikhitariank@health.missouri.edu
Martin
Renee Hebert
RH
Ruppel
Megan Baker
MB
Gillanders
William E
WE
Hoda
Rana
R
Schutte
Del H
del H
Callahan
Kathi
K
Mitas
Michael
M
Cole
David J
DJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D060785:Mammaglobin A; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood* / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism*; D014598:Uteroglobin / Q000097:blood* / Q000235:genetics*
D060785:Mammaglobin A; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C556448:SCGB2A2 protein, human; D014598:Uteroglobin