grade G2

The aim of this study was to define a gene expression signature capable of discerning breast tumors of grade 1 (G1) and grade 3 (G3) histology which might provide a more objective measure of grade with prognostic benefit for patients with G2 disease.

The hypothesis of this study is that a gene expression signature capable of discriminating low- and high-grade tumors might provide a more objective and clinically valuable measure of tumor grade with prognostic significance for patients with moderately differentiated cancer.

This dataset consists of two breast cancer cohorts: Uppsala (n=249) and Singapore (n=40).

The Uppsala cohort originally composed of 315 women representing 65% of all breast cancers resected in Uppsala County, Sweden, from January 1, 1987, to December 31, 1989. All sections were graded in a blinded fashion (H.N.) according to the Nottingham Grading System as described by Elston et al. The Uppsala tumor samples were approved for microarray profiling by the ethical committee at the Karolinska Institute, Stockholm, Sweden.

The Singapore samples were derived from patients operated on at the National University Hospital (Singapore) from February 1, 2000, through January 31, 2002. Routine clinical data were obtained from pathology reports, but no information on recurrence or cause of death was available. Tumor sections were graded by T.C.P. according to the Nottingham grading system as applied to the Uppsala cohort, with the following exception: Mitotic Index: 1 = low, if <8 mitoses; 2 = medium, if 9 to 16 mitoses; and 3 = high, if >16 mitoses (per 10 high-power fields); field diameter was 0.55 mm. Only histologic G2 samples were evaluated in this study. The Singapore samples were approved for microarray profiling by the Singapore National University Hospital ethics board.

All tumor samples were profiled on the Affymetrix U133A&B genechips. Microarray analysis of the Uppsala and Singapore samples was carried out at the Genome Institute of Singapore. All data were normalized using the global mean method (MAS5), and probe set signal intensities were natural log transformed and scaled by adjusting the mean signal to a target value of log 500.

Ivshina, Anna V., Joshy George, Oleg Senko, Benjamin Mow, Thomas C. Putti, Johanna Smeds, Thomas Lindahl, et al. “Genetic Reclassification of Histologic Grade Delineates New Clinical Subtypes of Breast Cancer.” Cancer Research 66, no. 21 (November 1, 2006): 10292–301. doi:10.1158/0008-5472.CAN-05-4414.

Elston, C. W., and I. O. Ellis. “Pathological Prognostic Factors in Breast Cancer. I. The Value of Histological Grade in Breast Cancer: Experience from a Large Study with Long-Term Follow-Up.” Histopathology 41, no. 3A (September 2002): 154–61.