Interobserver reproducibility of the Lagios nuclear grading system for ductal carcinoma in situ*1, *2

Sneige, Nour; Lagios, Michael D.; Schwarting, Roland; Colburn, William J.; Atkinson, E. Neely; Weber, Diane; Şahin, Ayşegül; Kemp, Bonnie L.; Hoque, Ashraful; Risin, Seymon; Sabichi, Anita L.; Boone, Charles W.; Dhingra, Kapil; Kelloff, Gary J.; Lippman, Scott M.

doi:10.1016/s0046-8177(99)90002-3

Cited by 45 publications

(42 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, this classification of DCIS is poorly reproducible among pathologists (3). Molecular studies, still based on a limited number of cases, have revealed some characteristics of high-grade DCIS, including the high frequency of ERBB2 overexpression, TP53 mutations, chromosomal 8p loss, and 1q gain (4 -9).…”

Section: /Ermentioning

confidence: 99%

Integrated Genomic and Transcriptomic Analysis of Ductal Carcinoma In situ of the Breast

Vincent‐Salomon

Lucchesi²,

Gruel³

et al. 2008

Clinical Cancer Research

150

104

View full text Add to dashboard Cite

Purpose: To gain insight into genomic and trancriptomic subtypes of ductal carcinomas in situ of the breast (DCIS). Experimental Design: We did a combined phenotypic and genomic analysis of a series of 57 DCIS integrated with gene expression profile analysis for 26 of the 57 cases. Results: Thirty-two DCIS exhibited a luminal phenotype; 21 were ERBB2 positive, and 4 were ERBB2/estrogen receptor (ER) negative with1harboring a bona fide basal-like phenotype. Based on a CGH analysis, genomic types were identified in this series of DCIS with the 1q gain/16q loss combination observed in 3 luminal DCIS, the mixed amplifier pattern including all ERBB2, 12 luminal and 2 ERBB2 -/ER -DCIS, and the complex copy number alteration profile encompassing 14 luminal and 1ERBB2 -/ER -DCIS. Eight cases (8 of 57; 14%) presented aTP53 mutation, all being amplifiers. Unsupervised analysis of gene expression profiles of 26 of the 57 DCIS showed that luminal and ERBB2-amplified, ER-negative cases clustered separately.We further investigated the effect of high and low copy number changes on gene expression. Strikingly, amplicons but also low copy number changes especially on 1q, 8q, and 16q in DCIS regulated the expression of a subset of genes in a very similar way to that recently described in invasive ductal carcinomas. Conclusions: These combined approaches show that the molecular heterogeneity of breast ductal carcinomas exists already in in situ lesions and further indicate that DCIS and invasive ductal carcinomas share genomic alterations with a similar effect on gene expression profile.

show abstract

Section: /Ermentioning

confidence: 99%

Integrated Genomic and Transcriptomic Analysis of Ductal Carcinoma In situ of the Breast

Vincent‐Salomon

Lucchesi²,

Gruel³

et al. 2008

Clinical Cancer Research

150

104

View full text Add to dashboard Cite

show abstract

“…Unfortunately, interobserver agreement in the classification of DCIS has not been consistent. The classification schemes that have for the most part proven to be reproducible are the Van Nuys classification and the method proposed by Lagios (Bethwaite et al, 1998;Douglas-Jones et al, 1996;Sneige et al, 1999). This is probably due to better results being reported when using a two-vs. three-tiered system, because of difficulty categorizing the middle categories (Shoker and Sloane, 1999).…”

Section: Prognostic Featuresmentioning

confidence: 99%

“…Poller et al (1994): Nottingham-Necrosis ϩ cytologic features ϩ architecture A. Comedo (pure) ϭ high-grade nuclei ϩ intraductal necrosis (90%) B. DCIS ϩ Necrosis (non-pure comedo) ϭ cribriform/micropapillary DCIS ϩ necrosis Ϫ high-grade cytology C. DCIS Ϫ Necrosis ϭ DCIS (as in B) Ϯ necrosis (0-Ͻ10%) 6. Silverstein et al (1995) Nevertheless, classification of DCIS by nuclear grade is prognostically important because as shown by most studies, the rate and time to recurrence are directly related to nuclear grade (Bellamy et al, 1989;Eusebi et al, 1994;Lagios et al, 1989;Silverstein et al, 1995, 1999, Sneige et al, 1999. However, there are few studies that have failed to show this relationship between nuclear grade and recurrence.…”

Section: Prognostic Featuresmentioning

confidence: 99%

Histologic classification of ductal carcinoma in situ

Jaffer

Bleiweiss

2002

Microscopy Res & Technique

View full text Add to dashboard Cite

Prior to the current mammographic era, ductal carcinoma in situ (DCIS) usually presented as a large mass, was classified morphologically by architecture, and treated by mastectomy. The introduction of screening mammography led to an increase in the incidence of DCIS, a decrease in the average size of DCIS, and an increased emphasis on its heterogeneous nature. Thus, a reproducible and prognostically relevant classification system for DCIS is necessary. The ultimate goal of this classification is proper selection of patients for whom lumpectomy would suffice rather than mastectomy. Features to evaluate include: extent and size of disease, adequacy of resection margins, and histology. While none of the proposed histological classification systems were endorsed at the recent Consensus Conference on the Classification of DCIS, nuclear grade was the most important feature common to most of them. Architecture was given secondary importance. By definition, DCIS is a non-invasive clonal proliferation of epithelial cells originating in the terminal duct lobular unit, which would be expected to be monomorphic; however, it is the degree of nuclear pleomorphism that is primarily used to separate DCIS into low, intermediate, and high grades. Architecturally, DCIS has been divided into the following types: comedo, solid, cribriform, micropapillary, and papillary. Different architectural patterns and grades may be present in a given particular case; however, some combinations of patterns occur more frequently than others. Interobserver studies have shown nuclear grading to be interpreted with greater consistency than architecture, and nuclear grading methods have correlated with biological and molecular marker studies.

show abstract

“…Interobserver reproducibility studies have also been performed to define the system that allows the greatest concordance in pathologic assessment (5)(6)(7)(8), with most advocating nuclear grade as the criterion that achieved the best agreement.…”

mentioning

confidence: 99%

Correlation of Nuclear Morphometry with Pathologic Parameters in Ductal Carcinoma In Situ of the Breast

et al. 2001

View full text Add to dashboard Cite

Morphometric features of nuclear perimeter, nuclear area, feret ratio, and feret circle were studied in a series of 64 cases of ductal carcinoma in situ (DCIS) of the breast in Singapore women. The results were compared with pathologic parameters of tumor size, nuclear grade, necrosis, cell polarization, and architectural pattern. There was statistically significant correlation between nuclear perimeter and area with all the pathologic parameters, with the strongest association observed for nuclear grade (P < .0001). Higher grade nuclei as assessed histologically were associated with larger nuclear area ( Ductal carcinoma in situ (DCIS) of the breast, generally regarded as the precursor of most invasive breast cancers, has increased dramatically in incidence, due primarily to mammographic screening (1). In Singapore, it was found to comprise 25% of screen-detected breast cancers (2), with 94% of DCIS lesions associated with radiologic calcifications (3). Because it is a heterogeneous lesion, pathological classification schemes that attempt to define its biologic potential in terms of local recurrence and progression to invasive carcinoma have evolved, and debate continues as to the best system to adopt (4). Interobserver reproducibility studies have also been performed to define the system that allows the greatest concordance in pathologic assessment (5-8), with most advocating nuclear grade as the criterion that achieved the best agreement.In this paper, we document the correlation of pathologic variables determined from routine macroscopic and microscopic assessment of DCIS lesions with morphometric nuclear features derived quantitatively from image analysis. The aims are to investigate the association between histologically assigned nuclear grade and quantitative nuclear parameters, confirm its reproducibility with an objective imaging system, and define the relationship of other pathologic criteria with the nuclear morphometric findings. MATERIALS AND METHODS Patients, Tumors, and Pathological EvaluationThe study population comprised 64 women diagnosed with DCIS of the breast between 1993 and 1999, obtained from the files of the Department of Pathology, Singapore General Hospital. Tissues were fixed in 10% buffered formaldehyde (pH 7.0), embedded in paraffin, sectioned at 4 m, and stained with hematoxylin and eosin (H&E). The pathological features analyzed were tumor size, nuclear grade, presence or absence of necrosis or cell

show abstract

Interobserver reproducibility of the Lagios nuclear grading system for ductal carcinoma in situ1, 2

Cited by 45 publications

References 19 publications

Integrated Genomic and Transcriptomic Analysis of Ductal Carcinoma In situ of the Breast

Integrated Genomic and Transcriptomic Analysis of Ductal Carcinoma In situ of the Breast

Histologic classification of ductal carcinoma in situ

Correlation of Nuclear Morphometry with Pathologic Parameters in Ductal Carcinoma In Situ of the Breast

Contact Info

Product

Resources

About