BREAST CANCER RESISTANCE PROTEIN - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 340

these discrepancies are likely to be due to the lack of standardized methods and the
lack of a uniform reference point.
Two studies reported contradictory results when measuring ABCG2 expression
in solid tumors by immunohistochemistry. Scheffer et al. examined protein expres-
sion in 34 paraffin-embedded untreated tumor samples from various sites and found
positive staining in only one small intestine adenocarcinoma sample. 125 In a study
of 150 paraffin-embedded untreated tumor samples, Diestra and colleagues reported
frequent ABCG2 expression. Highest levels were found in melanoma and tumors
of the digestive tract, endometrium, and lung. 161 Both cytoplasmic and membrane
staining was observed, raising some concern about specificity. However, this is the
most complete immunohistochemical study to date.
In a study of 43 untreated breast carcinoma samples, Kanzaki et al. reported low
ABCG2 gene expression as measured by RT-PCR, and no correlation with clinical
outcome. 162 Similarly, Faneyte et al. reported no detectable ABCG2 expression by
immunohistochemistry and no correlation between gene expression and survival. 126
Burger and colleagues, however, found that ABCG2 and ABCB1 gene expression cor-
related with response in anthracycline-treated patients, although expression did not
correlate with progression-free survival. 163 Since ABCG2 does not transport anthra-
cyclines significantly, it is difficult to discern why expression would correlate with
poor response.
Two studies have focused on ABCG2 expression in testicular tumors. Zurita et al.
examined protein expression in 56 paraffin-embedded tumor samples from patients
diagnosed with advanced testicular germ cell tumors. Strong and intermediate expres-
sion was observed in 86 and 7% of samples, respectively. 164 They found no correlation
between ABCG2 expression and clinical outcome when patients were treated with
platinum-based chemotherapy. 164 The second study found that seminoma and non-
seminoma testicular tumor samples from untreated patients expressed ABCG2 when
assessed by immunohistochemistry using the BXP-21 antibody, whereas testicular
lymphoma samples did not. 134
Studies demonstrating an interaction between tyrosine kinase inhibitors such as
gefitinib and ABCG2 led Theou and colleagues to examine ABCG2 via Western blot
in tumor samples obtained from 21 patients with gastrointestinal stromal tumors and
three patients with leiomyosarcomas. 165 They found no expression of ABCG2 in any
of the samples; however, detection of protein expression by immunoblotting is not a
sensitive method and may not detect low but clinically relevant levels of ABCG2.
Yoh et al. examined ABCG2 expression in 72 formalin-fixed paraffin-embedded
samples obtained from patients diagnosed with non-small cell lung carcinoma before
chemotherapy. 166 Of the 72 samples, 33 (46%) were ABCG2 positive. ABCG2 ex-
pression correlated with shorter progression-free survival and overall survival when
patients were treated with platinum-based chemotherapy. This finding needs to be
reproduced and verified with a different method, since platinum compounds are not
ABCG2 substrates.
It is likely that the discordant results reported for ABCG2 expression in cancer
are due to the lack of standardized methods of detection. As demonstrated by a
1994 workshop devoted to determining standardized methods for detection of Pgp,