Relationship of cell proliferation (Ki-67) to 99mTc-(V)DMSA uptake in breast cancer.
BACKGROUND
The aim of the present study was to identify the relationships between the uptake of radiotracers - namely pentavalent dimercaptosuccinic acid [(V)DMSA] and sestamibi (MIBI) - and the following parameters in primary breast cancer: steroid receptor concentrations (i.e. estrogen receptor [ER] and progesterone receptor [PR]), Ki-67 expression, tumor size, tumor grade, age, and levels of expression of p53 and c-erbB-2. In addition, by multivariate regression analysis, we further isolated those factors with independent associations with (V)DMSA and/or MIBI uptake in primary breast cancer.


METHODS
Thirty-four patients with histologically confirmed breast carcinoma underwent preoperative scintimammography with technetium-99m (99mTc)-(V)DMSA and/or 99mTc-MIBI in consecutive sessions 10 and 60 min after administration of 925-1110 MBq of each radiotracer. The tumor-to-background ratio was calculated and correlated with the presence of ER, PR, Ki-67, tumor size, tumor grade, p53, and c-erbB-2. ER, PR, p53, and c-erbB-2 were determined immunohistochemically. The analysis included tumor-to-background ratio of (V)DMSA and MIBI uptake as dependent and all of the other parameters as independent variables.


RESULTS
Correlation was positive between Ki-67 and (V)DMSA (r = 0.37 at 10 min, P = 0.038; r = 0.42 at 60 min, P = 0.018) and inverse between PR and (V)DMSA uptake (r = -0.46 at 10 min, P = 0.010; r = -0.51 at 60 min, P = 0.003). Multivariate regression analysis demonstrated a positive correlation between Ki-67 and (V)DMSA at 60 min (P = 0.045). Ki-67 was not significantly correlated with MIBI uptake, whereas tumor size was positively correlated with MIBI uptake at 60 min both in univariate (r = 0.45, P = 0.027) and multivariate analysis (P = 0.024). Negative correlations were observed between (V)DMSA uptake and ER, as well as between ER/PR and MIBI uptake, but these were not significant.


CONCLUSIONS
Ki-67 appears to represent the major independent factor affecting (V)DMSA uptake in breast cancer. Tumor size was the only independent parameter influencing MIBI uptake in breast cancer. (V)DMSA appears to have an advantage over MIBI in that it can be used to visualize tumors with intense proliferative activity, and thus it can identify those tumors that are more aggressive.
Department of Nuclear Medicine, Alexandra University Hospital, Athens, Greece. vpap@spark.net.gr
Vassilios J
VJ
Papantoniou
Michael A
MA
Souvatzoglou
Varvara J
VJ
Valotassiou
Androniki N
AN
Louvrou
Constantina
C
Ambela
John
J
Koutsikos
Dimitrios
D
Lazaris
Julie K
JK
Christodoulidou
Maria G
MG
Sotiropoulou
Maria J
MJ
Melissinou
Aris
A
Perperoglou
Spyridon
S
Tsiouris
Cherry J
CJ
Zerva
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008327:Mammography / Q000379:methods; D008875:Middle Aged; D011877:Radionuclide Imaging / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000378:metabolism*; D017256:Technetium Tc 99m Sestamibi / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D017256:Technetium Tc 99m Sestamibi; D016159:Tumor Suppressor Protein p53