Maspin and mammaglobin genes are specific markers for RT-PCR detection of minimal residual disease in patients with breast cancer.
BACKGROUND
This study evaluates the specificity of some reverse-transcriptase polymerase chain reaction (RT-PCR) assays for the detection of residual tumor cells in breast cancer patients. The following markers have been analysed: carcinoembryonic antigen (CEA), cytokeratins (CK19 and CK20), polymorphic epithelial mucin (MUC-1), epidermal growth factor receptor (EGFR), maspin, and mammaglobin. RT-PCR was employed to detect breast cancer cells in peripheral blood (PB), bone marrow (BM), and stem cell leukoaphereses (PBPC).


METHODS
We evaluated the specificity of our RT-PCR assays on a panel of breast cancer specimens (n = 30), on PBPC in patients undergoing high-dose chemotherapy (n = 38), on BM (n = 7) and PB (n = 5) samples obtained from patients with breast cancer. Marrow cells, PB, and PBPC from normal subjects or hematological tumor patients were tested as negative controls.


RESULTS
Only maspin and mammaglobin met the criteria of sensitivity and specificity required for the detection of residual disease; they were expressed in 80% and 97% of breast cancer specimens, respectively, and not expressed in normal controls. CK19, CK20. EGFR, MUC-1, and CEA were sometimes expressed in normal blood cells and/or hematological tumors.


CONCLUSIONS
Our data support the notion that maspin and mammaglobin are useful markers for RT-PCR detection of minimal residual disease (MRD) in breast cancer patients, and that perspective clinical studies are needed to determine wether RT-PCR assays will be useful in assessing prognosis, tailoring therapy, or developing new strategies for ex vivo purging.
Corradini
P
P
Department of Hematology, Istituto Scientifico H. S. Raffaele, Milan, Italy. paolo.corradini@unimi.it
Voena
C
C
Astolfi
M
M
Delloro
S
S
Pilotti
S
S
Arrigoni
G
G
Bregni
M
M
Pileri
A
A
Gianni
A M
AM
D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002272:Carcinoembryonic Antigen / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007633:Keratins / Q000235:genetics; D060785:Mammaglobin A; D018396:Mucin-1 / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D018299:Neoplasms, Ductal, Lobular, and Medullary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015843:Serpins / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014598:Uteroglobin / Q000235:genetics*
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D060785:Mammaglobin A; D018396:Mucin-1; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; C556448:SCGB2A2 protein, human; C085344:SERPIN-B5; D015843:Serpins; D007633:Keratins; D014598:Uteroglobin; D066246:ErbB Receptors