|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Originally published as JCO Early Release 10.1200/JCO.2008.21.7646 on April 20 2009 © 2009 American Society of Clinical Oncology.
Cancer Is HeterogeneousDepartment of Pathology, Centre René-Huguenin, Saint-Cloud, France To the Editor: Badve et al's1 recently published article concerns a comparison of immunohistochemistry (IHC) with a biologic method of hormonal receptors in a patient population enrolled in a clinical trial of two different chemotherapies. This method, that measures mRNA by polymerase chain reaction on fixed, paraffin-embedded tissue fragments has the advantage, relative to other nonmorphological techniques of not requiring a frozen fragment (ie, dextran charcoal, ligand binding, and micro-arrays). This method increases the number of cases that can be analyzed, retrospectively if necessary. But the analysis is subject to the same problems as other biologic methods. There were detailed descriptions of when IHC was compared with biologic methods and chosen as the standard for hormonal receptors, and it is surprising that some of these problems were mentioned neither in the discussion nor in the accompanying editorial.2 First, the amount of tumor varies widely from one patient to the next, owing to several factors: (1) the sample type (ie, core needle biopsy, surgical biopsy, and so on); (2) tumor size (increasingly small, owing to routine breast cancer screening); and (3) the proportion of viable tumor cells present within the sample. Some tumors are paucicellular, such as infiltrating lobular carcinoma in its classical form, or accompanied by a particularly strong stromal reaction, whether fibrous (as in ductal carcinoma, not otherwise specified) or inflammatory (the characteristic example being the medullary form). It can also be secondary because of necrotic changes, whether spontaneous (some forms of basal-like carcinoma) or induced by fine-needle aspiration, core-needle biopsy, or guide-wired localization. By comparison, IHC analysis is possible in all these circumstances, even on a few infiltrating tumor cells. This is all the more important as tumor volume continues to fall with the uptake and improvement of routine screening in many countries. In addition, with the extension of the indications of core biopsy before resection, the tumor is no longer whole but fragmented, part being present in the biopsy samples and part in the surgical specimen, each having a reduced volume. It is interesting to note that in Oncotype DX assay (Genomic Health, Redwood City, CA) studies of core-needle biopsy material, the rate of nonassessable samples ranged from 6%3 to 17%4 and more than 20%.5 As for the biologic quality of the sample, it is fixed, and this makes it subject to variations in the speed and duration of fixation. One major advance in IHC was antigenic unmasking, as it avoided the influence of the fixation time, especially hyperfixation. mRNA (analyzed by Oncotype DX) is far more fragile than protein (analyzed by IHC), explaining why most studies use fresh samples. If one examines the different Oncotype Dx publications, the proportion of nonassessable cases, due to insufficient mRNA or to poor amplification quality, range from 1.1%6 to 32.6%,7 reflecting the influence of the fixation conditions. Finally, the analyzed material is a homogenate of infiltrating cells, cells of the in situ component, inflammatory cells, normal tissues, and the stromal reaction. It is therefore impossible to distinguish (1) the intraductal component and the infiltrating component, the expression of which sometimes differs and that are too intimately intermingled to separate by macrodissection; and (2) tumors with heterogeneous hormone receptor or human epidermal growth factor receptor 2 status, as the analysis provides only the mean mRNA level. These tumors represent at least 5%. This type of tumor raises specific therapeutic and diagnostic issues: when they are identified, it is recommended to sample metastases, if present, in order to characterize the nature of the malignant component and to adapt treatment appropriately. These advantages, in addition to issues of cost and tissue availability, led to IHC methods being preferred to biologic methods, and this is still the case. A prognostication industry is emerging with the development of prognostic and predictive tests, but it is crucial the debate remain based on scientific evidence and cost effectiveness. Finally, as the tumor volume continues to fall because of routine screening, it will no longer be technically feasible to use several methods. The most relevant and least costly method(s) will have to be chosen. AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Badve SS, Baehner FL, Gray RP, et al: Estrogen- and progesterone-receptor status in ECOG 2197: Comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory. J Clin Oncol 26:2473–2481, 2008. 2. Allred DC: Problems and solutions in the evaluation of hormone receptors in breast cancer. J Clin Oncol 26:2433–2435, 2008. 3. Gianni L, Zambetti M, Clark K, et al: Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol 23:7265–7277, 2005. 4. Chang JC, Makris A, Gutierrez MC, et al: Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients. Breast Cancer Res Treat 108:233–240, 2008.[CrossRef][Medline] 5. Mina L, Soule SE, Badve S, et al: Predicting response to primary chemotherapy: Gene expression profiling of paraffin-embedded core biopsy tissue. Breast Cancer Res Treat 103:197–208, 2007.[CrossRef][Medline] 6. Paik S, Shak S, Tang G, et al: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817–2826, 2004. 7. Esteva FJ, Sahin AA, Cristofanilli M, et al: Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy. Clin Cancer Res 11:3315–3319, 2005.
Related Article
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
