title: Grading ductal carcinoma in situ of the breast using an automated proliferation index.
abstract: Tumor grade, size and margin status are the most significant factors in predicting the behavior of ductal carcinoma in-situ (DCIS). The inclusion of necrosis and nuclear grade in the grading of DCIS has demonstrated a fair but suboptimal agreement between pathologists. The grading of DCIS was studied and compared to the Van Nuys (VN) system, by using our newly proposed unifying "nuclear grade + proliferation index (N+P) grading system for invasive carcinomas. 162 DCIS tumors were studied including 49 VN I, 31 VN II, and 82 VN III cases. The VN and N+P systems were compared with each other and correlated with tumor size, ER, PR, p53, Her-2, EGFR, Bcl-2, p27 and p21 status. The two systems demonstrated similar frequencies for the different grades and an agreement with each other for all of the biomarkers studied. The greatest difference between the two systems was observed for those tumors initially classified as VN II (94% being down-graded to N+P I) and VN III (80% being down-graded to N+P II). These results suggest that the N+P system, combining nuclear grade with automated MIB-1 count, is a potentially valid and reproducible grading system for both non-invasive and invasive mammary carcinomas. It is automated, less subjective in assessing mitotic activity and necrosis and correlates with other prognostic biomarkers.
authors.affiliation: Professor of Pathology, Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Stasik
authors.forename: Marilyn
authors.initials: M
authors.lastname: Davis
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Kimler
authors.forename: Fang
authors.initials: F
authors.lastname: Fan
authors.forename: Ivan
authors.initials: I
authors.lastname: Damjanov
authors.forename: Patricia
authors.initials: P
authors.lastname: Thomas
authors.forename: Ossama W
authors.initials: OW
authors.lastname: Tawfik
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D044767:Ubiquitin-Protein Ligases / Q000032:analysis
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D066246:ErbB Receptors; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; C493956:CDKN1A protein, human; C413374:p27 antigen; C513496:MIB1 ligase, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human