title: Prognostic relevance of histological grade and its components in node-negative breast cancer patients.
abstract: Available results highlight the lack of good level of evidence studies on the pure prognostic value of histological grade. In the present study, the prognostic relevance of histological grade and of its three components, tubule formation, nuclear pleomorphism and mitotic count, was analyzed in a series of 372 patients with node-negative breast cancer treated with locoregional therapy alone until early relapse. Histological grade was determined blindly by two observers and discordance between evaluations was resolved after joint review using a multihead microscope. No relation was observed between histological grade and any of its three components and disease-free survival. Conversely, a significant relation was observed between histological grade and distant metastasis-free survival (at 6 years, 94, 86 and 76% for grades 1, 2 and 3, respectively, P=0.013) as well as overall survival (98, 90 and 86%, P=0.001). A breakdown analysis as a function of the three components showed that neither tubule formation nor nuclear pleomorphism was associated with prognosis, and only mitotic count strongly influenced both distant metastasis-free survival (91, 82 and 74%, P=0.014) and overall survival (97, 87 and 85%, P=0.011). Histological grade suffers from a much higher subjectivity than any other microscopic evaluation of biomarkers as it is the sum of three different morphological features. Within the Italian Network for Quality Assessment of Tumor Biomarkers program we observed that histological grade is an independent prognostic variable, but also that this role is ascribable only to the number of mitotic figures. In conclusion, due to the ever smaller size of diagnosed breast cancers, resulting in less cancer tissue for biofunctional and molecular analysis, mitotic count evaluated under strict quality control conditions seems to be an accurate and feasible prognostic variable.
authors.affiliation: Division of Oncology and Diagnostics, Pierantoni Hospital, Forlì, Italy. res.onco@ausl.fo.it
authors.forename: Annalisa
authors.initials: A
authors.lastname: Volpi
authors.forename: Francesco
authors.initials: F
authors.lastname: Bacci
authors.forename: Angelo
authors.initials: A
authors.lastname: Paradiso
authors.forename: Luca
authors.initials: L
authors.lastname: Saragoni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.forename: Monica
authors.initials: M
authors.lastname: Ricci
authors.forename: Mirella
authors.initials: M
authors.lastname: Aldi
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bianchi
authors.forename: Pietro
authors.initials: P
authors.lastname: Muretto
authors.forename: Fiorella
authors.initials: F
authors.lastname: Nuzzo
authors.forename: Gianni
authors.initials: G
authors.lastname: Simone
authors.forename: Anita
authors.initials: A
authors.lastname: Mangia
authors.forename: Francesco
authors.initials: F
authors.lastname: Schittulli
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D008940:Mitotic Index; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone