Circulating Tumor Cells Are Potential Alternative to Biopsy

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From Medscape Medical News

Circulating Tumor Cells Are Potential Alternative to Biopsy

Roxanne

October 1, 2010 ­ Circulating tumor cells (CTCs)

could prove to be an alternative to biopsies for

assessing tumor tissue for biomarker status.

According to new data presented at the 4th

American Association for Cancer Research

International Conference on Molecular Diagnostics

in Cancer Therapeutic Development in Denver,

Colorado, HER2 status derived from CTCs from

breast cancer patients was generally concordant

with that derived from tumor tissue.

CTCs present a very intriguing opportunity to

look at biomarkers, obviating the need for

biopsy, explained first author Siminder Kaur

Atwal, PhD, senior research associate at Genentech, during a press briefing.

" CTCs can also provide real-time information

about the disease, acting as a liquid biopsy, "

she said, " and it can be done with a simple blood draw. "

This makes it a much less invasive procedure than

tumor biopsy; CTCs can easily be obtained as part

of routine blood work, Dr. Atwal added. " CTCs can

also tell you the current status of the patient's

disease, which may be different from archival tissue. "

In addition, comparing CTCs collected prior to

treatment with those collected during repeated

sampling allows biomarkers to be monitored during the course of treatment.

Previous research has looked at using CTCs for

diagnosis, prognostic indicators, and predicting

response to therapy. As

<http://www.medscape.com/viewarticle/720561>reported

previously by Medscape Medical News, CTCs have

been discovered in men with early-stage prostate

cancer. One study, also

<http://www.medscape.com/viewarticle/563392>reported

by Medscape Medical News, demonstrated that the

detection of CTCs after treatment might indicate

that the patient is more likely to develop

metastases, and so might warrant repeat and aggressive chemotherapy.

There has also been great interest in developing

tools to effectively capture CTCs, as Medscape

Medical News has

<http://www.medscape.com/viewarticle/586100>previously reported.

Platform Efficiency Similar, Dependent on EpCAM Level

For their study, Dr. Atwal and colleagues

compared CTC capture platforms ­ the CellSearch

platform, which has been approved by the US Food

and Drug Administration as a prognostic assay,

and 2 CTC biochip platforms. Their goals were to

compare the platforms for CTC detection, to

evaluate whether biomarkers can be detected in

CTCs, and to compare biomarker status in CTCs and matched tumor tissue.

Using tumor cell lines spiked into whole blood,

the authors compared HER2 status in CTCs with

that in archival tumors, because " HER2 testing is

the gold standard in biomarker validation and is

typically evaluated in tumor tissue by

[immunohistochemistry] and/or [fluorescence in

situ hybridization], " the authors write

In addition, they attempted to detect epidermal

growth-factor receptor (EGFR) protein expression

in CTCs from patients with lung cancer.

They found that CellSearch and the newer biochip

platforms offered similar efficiency. The authors

also noted that capture efficiency was dependent

on the level of epithelial cell adhesion

molecules (EpCAM), which are present in tumor

cells but absent in white blood cells.

Amenable to Biomarker Analysis

Dr. Atwal and her colleagues were able to

demonstrate that captured CTCs are amenable to

biomarker analyses such as HER2 status,

quantitative reverse-transcription PCR for breast

cancer subtype markers, KRAS mutation detection,

and EGFR staining by immunofluorescence. HER2

status in CTCs was generally concordant with that

from patient tumor tissue (89%), although in one

subset of patients (11%), HER2 status had changed

from the primary tumor at diagnosis.

Unexpectedly, the authors found that CTC counts

were higher in estrogen-receptor-positive

patients than in HER2-positive and

triple-negative patients, despite the more aggressive phenotype.

An explanation for this might be the low EpCAM

expression of basal-like molecular subtypes of

breast cancer, and a more mesenchymal phenotype,

they write. " CTCs will likely not be efficiently

captured using EpCAM alone in tumors that arise from this subtype. "

The results also showed that the cell-surface

expression of EGFR can be quantitated in CTCs

from metastatic lung cancer patients.

" These results are encouraging because they

support the use of CTCs for HER2 testing, and we

hope to establish a role for CTC testing, " said

Dr. Atwal. " But a limitation of these platforms

is that CTC capture efficiency is dependent on

EpCAM expression, which we know can vary in different tumor types. "

Some improvements are necessary in CTC detection

and capture before the technology can be

generally useful in clinical biomarker analysis,

she noted. An example would be an antibody

cocktail with mesenchymal markers, along with

EpCAM, which could be used to improve the capture of CTCs.

" There is a major need for a noninvasive approach

to characterize patient tumors and to assess

response to therapy. In exciting preliminary

studies, Dr. Atwal and colleagues have

implemented rigorous approaches that demonstrate

that CTCs can offer a real-time view of changes

in the tumor, " Gordon B. Mills, MD, PhD, chair of

the Department of Systems Biology at the

University of Texas M.D. Cancer Center

in Houston, told Medscape Medical News.

" If validated in future studies, this could

provide exciting and important approaches to

implement personalized therapy, " he added.

4th American Association for Cancer Research

International Conference on Molecular Diagnostics

in Cancer Therapeutic Development (AACR-MDCTD):

Abstract PR3. Presented September 28, 2010.