Prognostic impact of ANX7-GTPase in metastatic and HER2-negative breast cancer patients.
OBJECTIVE
ANX7-GTPase located on chromosome 10q21 is significantly altered and associated with hormone-refractory metastatic prostate cancers. Therefore, we investigated whether levels of ANX7 correlate with breast cancer progression and survival


METHODS
A diagnostic tumor tissue microarray containing 525 human breast tissue specimens at different stages of the disease was assayed for ANX7 using immunocytochemical methods with ANX7 monoclonal antibody. A separate prognostic tumor tissue microarray containing 553 human breast tissue specimens annotated with clinicopathological parameters was assayed for ANX7, HER2, estrogen receptor, progesterone receptor, and p53 protein.


RESULTS
We report here for the first time that the expression of ANX7-GTPase is significantly enhanced and associated with the presence of metastatic disease (P < 0.0001) in the 525 human breast tissue specimens analyzed. Furthermore, using a separate 553 case retrospective prognostic tumor tissue microarray, we found that increased ANX7 expression is also significantly associated with poor overall patient survival (P < 0.014). This is particularly true when restricted to patients in whom the BRE clinical grade is 2 (P < 0.001) or for whom there is a lack of HER2 expression (P < 0.002). Finally, Cox regression analysis shows that as the expression of ANX7 rises, the probability of survival decreases by more than 10-fold for those patients with HER2-negative tumors. These latter patients represented 66% of the population affected with breast cancer in this study.


CONCLUSIONS
High levels of ANX7 in tumor correlate strongly with poor survival of HER2-negative patients and the most aggressive forms of breast cancer. This is the first study to demonstrate that ANX7 antibody has the potential for development into an in vivo diagnostic and therapeutic tool. This simple and reliable immunohistochemical assay may therefore become an important biomarker for metastatic breast cancer diagnosis and management of HER2-negative breast tumor patients.
Srivastava
Meera
M
Department of Anatomy, Physiology and Genetics and Institute for Molecular Medicine, Uniformed Services University School of Medicine, Bethesda, Maryland 20814, USA. msrivastava@usuhs.mil
Bubendorf
Lukas
L
Raffeld
Mark
M
Bucher
Christoph
C
Torhorst
Jochen
J
Sauter
Guido
G
Olsen
Cara
C
Kallioniemi
Olli P
OP
Eidelman
Ofer
O
Pollard
Harvey B
HB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017310:Annexin A7 / Q000096:biosynthesis* / Q000737:chemistry; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020558:GTP Phosphohydrolases / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D012044:Regression Analysis; D012306:Risk; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D017310:Annexin A7; D014408:Biomarkers, Tumor; D020558:GTP Phosphohydrolases; D018719:Erb-b2 Receptor Tyrosine Kinases