Some Grade IIs have a much worse prognosis than others. At San Antonio many thought the term "grade 2" meant absolutely nothing and should be abandoned.
The histologic grade (a semi-subjective value judged by a pathologist based on the appearance under the microscope of the slice of the tumor-how "angry" the cells look, how many appear to be dividing, etc) has very little to do with the genes, proteins and pathways which drive how tumors behave. How long it will take for the average oncologist to get access to gene expression profiles is unknown, although in the latest NIH budget there is money for discovering if cancer can be treated better and more cost-effectively if gene and/or protein profiling were carried out.
1: J Natl Cancer Inst. 2006 Feb 15;98(4):262-72. Related Articles, Links
Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.
Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, Nordgren H, Farmer P, Praz V, Haibe-Kains B, Desmedt C, Larsimont D, Cardoso F, Peterse H, Nuyten D, Buyse M, Van de Vijver MJ, Bergh J, Piccart M, Delorenzi M.
Functional Genomics and Translational Research Unit, Universite Libre de Bruxelles, Brussels, Belgium.
christos.sotiriou@bordet.be
BACKGROUND: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%-60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profiles of breast cancers and whether such profiles could be used to improve histologic grading. METHODS: We analyzed microarray data from 189 invasive breast carcinomas and from three published gene expression datasets from breast carcinomas. We identified differentially expressed genes in a training set of 64 estrogen receptor (ER)-positive tumor samples by comparing expression profiles between histologic grade 3 tumors and histologic grade 1 tumors and used the expression of these genes to define the gene expression grade index. Data from 597 independent tumors were used to evaluate the association between relapse-free survival and the gene expression grade index in a Kaplan-Meier analysis. All statistical tests were two-sided. RESULTS: We identified 97 genes in our training set that were associated with histologic grade; most of these genes were involved in cell cycle regulation and proliferation. In validation datasets, the gene expression grade index was strongly associated with histologic grade 1 and 3 status; however, among histologic grade 2 tumors, the index spanned the values for histologic grade 1-3 tumors. Among patients with histologic grade 2 tumors, a high gene expression grade index was associated with a higher risk of recurrence than a low gene expression grade index (hazard ratio = 3.61, 95% confidence interval = 2.25 to 5.78; P < .001, log-rank test). CONCLUSIONS: Gene expression grade index appeared to reclassify patients with histologic grade 2 tumors into two groups with high versus low risks of recurrence. This approach may improve the accuracy of tumor grading and thus its prognostic value.
PMID: 16478745 [PubMed - in process]
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