Histologic Grading of Breast Cancer: Linkage of Patient Outcome with Level of Pathologist Agreement

Abstract

In the histologic grading of invasive breast cancer with the Nottingham modification of the ScarffBloom-Richardson grading scheme (NSBR), it has been found that when pathologists disagree, they tend not to disagree by much. However, if tumor grade is to be used as an important parameter in making treatment decisions, then even this generally small degree of pathologist variability in assessing grade needs to be correlated with patient outcome.Findings from the Nottingham/Tenovus Primary Breast Cancer Study were used for patient outcome data. Kaplan-Meier survival curves were constructed for NSBR scores grouped according to the level at which pathologists tend to agree in assessing grade, from a reproducibility perspective. For example, if a given tumor were assessed by several pathologists as having either an NSBR score of 5 or 6, then what is the correct score-the intermediategrade Score 6 assessments or the low-grade Score 5 assessments? By "regrouping" the Nottingham outcome data such that data from patients with Score 5 tumors are grouped with patients having Score 6 tumors (a 5-6 group), then the level in which the pathologists agreed with each other (that the tumor was either score 5 or 6) is better matched with patient outcome.In response to the above example, it was not surprising to find that patients with Score 5-6 tumors had a probability of survival between the established low and intermediate NSBR final combined grades. However, it is the discussion of this approach that highlights that optimal use of grading requires awareness of the level of pathologist agreement and understanding the value of pathologists' reaching consensus in assessments. Also, knowledge of possible clinical decision thresholds can help in providing relevant interpretations of grading results.

Gene expression profiles of human breast cancer progression

“…Together, these unique signatures may underlie the molecular basis of the current pathological grading systems for breast cancer. Such systems rely mainly on histomorphological criteria, which, although highly successful in discriminating grade I from grade III tumors, are inadequate to score grade II tumors consistently (4). This difficulty may be explained by the overlapping nature of grade II signature with those of grade I and grade III.…”

“…DCIS was classified according to the European classification scheme (5): low-grade DCIS is characterized by a clinging, cribriform, or micropapillary proliferation of small, monomorphic cells with rare mitoses, whereas high-grade DCIS is characterized by a solid or clinging proliferation of large, pleomorphic cells with frequent mitoses. IDC was classified according to by the Nottingham combined histological grade (4). Estrogen receptor (ER) and progesterone receptor (PR) expression were determined by immunohistochemical staining (negative when none of the tumor cell nuclei showed staining), and Her-2 expression determined by immunohistochemistry or fluorescence in situ hybridization (FISH).…”

“…To further characterize DCIS and IDC with respect to this heterogeneity, several tumor-grading systems have been created. Such systems are used clinically to subtype the stages of DCIS and IDC into three tumor grades in which grade I, II, and III lesions correspond to well, moderately, and poorly differentiated breast tumors, respectively (4,5). Tumor grade has been a highly valuable prognostic factor for breast cancer, as poorly differentiated, high-grade DCIS or IDC lesions are associated with significantly poorer clinical outcome (4)(5)(6).…”

Nuclear localisation of LASP-1 correlates with poor long-term survival in female breast cancer

“…Grading of malignancy of ductal carcinomas was evaluated according to the Scarff, Bloom and Richardson criteria as suggested by Nottingham City Hospital Pathologists (Dalton et al, 2000). Tumour staging was performed according to parameters of the TNM system (Singletary and Connolly, 2006).…”

Learning invariant features of tumor signatures

“…These sections are typically rich in content since various cell types, cellular organization, cell state and health, and cellular secretion can be characterized by a trained pathologist in spite of inter-and intraobserver variations [3]. A recent review for the analysis and application of H&E sections can be found in [4,5]; however, from our perspective, three key concepts have been introduced to establish the trend and direction of the research community.…”