Apoptosis - associated genes and their role in predicting responses to neoadjuvant breast cancer treatment.
BACKGROUND
Neoadjuvant chemotherapy is used in the treatment of breast carcinoma because it substantially reduces the size of the primary tumor and lymph node metastases. The present study investigated biomarkers that can predict a pathologic response to the therapy.


METHODS
The role of apoptosis in regression of the tumors after neoadjuvant chemotherapy was determined by TUNEL and anti-active caspase 3 assay. The transcriptional profile of 84 key apoptosis genes was evaluated in both pre-therapeutically obtained tumor tissue by core needle biopsy and in specimens removed by final surgery, using a pathway-specific real-time PCR assay. Obtained data were analyzed by hierarchical cluster analysis and correlation analysis. The immunohistochemical profile of each tumor was determined using the standard ABC method.


RESULTS
On the basis of a hierarchical cluster analysis of 13 significantly changed genes, we divided patients into good and poor prognosis groups, which correlate well with progression-free survival. In the good prognosis group, we found a statistically significant down-regulation of the expression of MCL1 and IGF1R genes after neoadjuvant treatment. We also found a statistically significant overexpression of BCL2L10, BCL2AF1, CASP8, CASP10, CASP14, CIDEB, FADD, HRK, TNFRSF25, TNFSF8 and CD70 genes. In contrast, we found up-regulation of IGF1R after the treatment in the group with poor prognosis.


CONCLUSIONS
Gene expression profiling using real-time PCR assay is a valuable research tool for the investigation of molecular markers, which reflect tumor biology and treatment response.
Institute of Pathology, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. Daniel.Tvrdik@vfn.cz
Daniel
D
Tvrdík
Helena
H
Skálová
Pavel
P
Dundr
Ctibor
C
Povýšil
Zuzana
Z
Velenská
Adéla
A
Berková
Libor
L
Staněk
Luboš
L
Petruželka
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016133:Polymerase Chain Reaction; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins