Analysis of reproducibility of subjective grading systems for breast carcinoma.

Stenkvist, Björn; Westman-Naeser, Sighild; Vegelius, Jan; Holmquist, Jan; Nordin, Bo; Bengtsson, Ewert; Eriksson, Olle

doi:10.1136/jcp.32.10.979

Cited by 130 publications

(42 citation statements)

References 9 publications

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“…The assessment of histological grade has been criticised because of its subjective nature (Stenkvist et al, 1979). There can also be many problems in using immunohistochemistry as a prognostic tool.…”

Section: Discussionmentioning

confidence: 99%

Assessment of milk fat globule membrane antibodies and lectins as markers of short-term prognosis in breast cancer

Walker

1990

Br J Cancer

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Summary The milk fat globule membrane antibodies HMFGI, HMFG2, NCRC 11 and four of the Mam 6 series, and the lectins peanut agglutinin, wheat germ agglutinin, Concanavalin A, Lotus tetragonolobus and Ulex europaeus I have been applied to 115 stage I and II breast carcinomas (median follow up = 36 months) to assess their value as prognostic markers. Of the milk fat globule membrane antibodies only NCRC 11 staining showed a relationship to development of recurrent disease and overall survival, but this did not act as an independent indicator over and above that provided by histological grade. None of the lectins gave prognostic information, including those whose binding related to node status or grade. It is concluded that for short-term prognosis none of the markers-can given independent prognostic information over and above that provided by histological evaluation.The biological behaviour of breast carcinoma can vary considerably such that there are patients with a very poor prognosis (Blamey et al., 1979) and those who remain free from disease for over 20 years (Brinkley & Haybittle, 1975). Factors such as the extent of spread (both nodal and distant) at the time of presentation are important in predicting behaviour, and this forms the basis of staging systems. However, changes in surgical practice with a reduction in axillary node sampling, plus a need to subdivide node negative early stage patients into poor or good risk categories means that there is a need to maximise the amount of prognostic information which can be obtained from the primary tumour.The immunohistochemical assessment of primary tumours for the expression of various markers of potential prognostic value is one such approach. The use of antibodies to different components of the milk fat globule membrane has resulted in conflicting reports. Wilkinson et al. (1984) concluded that the antibody HMFG1 could be useful as a prognostic indicator, but Berry et al. (1985) found no relationship between the extent of staining with HMFG1 and HMFG2 and survival. Ellis et al. (1985, 1987) used the monoclonal antibody NCRC 11, which although raised against a breast carcinoma metastasis detects high molecular weight glycoproteins similar-to those recognised by antibodies raised against the milk fat globule membrane. They found a clear relationship between immunoreactivity of carcinomas and the clinical course of the disease. Angus et al. (1986), however, using the same antibody, did not find a statistically significant relationship with prognosis. Direct comparison of the staining obtained with HMFG1, HMFG2 and NCRC 11 antibodies for the same group of carcinomas and their relationship to prognosis has not been published.Another approach which has -been evaluated for its prognostic value has been the binding of lectins to primary tumours. Greater reactivity of carcinomas with Helix pomatia was reported as relating to poorer survival (Fenlon et al., 1987;Leathem & Brooks, 1987) as did Ulex europaeus I binding (Fenlon et al., 1987).In the present study a grou...

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Section: Discussionmentioning

confidence: 99%

Assessment of milk fat globule membrane antibodies and lectins as markers of short-term prognosis in breast cancer

Walker

1990

Br J Cancer

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“…It is confusing that differentiation is considered together with these factors since it is not known to what extent they contribute independently to the prognostic outcome. This is further underlined in a recent truncated component analysis (17) showing that they do not seem to describe the same biologic phenomenon. In addition, in one study (4) only one expression of differentiation-tubule formation is evaluated, cohesiveness of cell populations of different tumors obtained from the same organ.…”

Section: Key Terms: Breast Cancer Differentiation Morphometrymentioning

confidence: 99%

A morphometric expression of differentiation in fine‐needle biopsies of breast cancer

et al. 1981

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An automated method of particle sizing in fine-needle biopsies of human breast carcinomas is described. The average sue of clusters of cells aspirated from breast carcinomas was strongly correlated with cytologic differentiation of the tumors and also with the recurrence rate 3 years after mastectomy so that smaller cluster size w a s associated with poor differentiation and a poor prognostic outcome. It thus seems possible to express in quantitative terms the degree of differentiation of breast carcinomas. Key terms: Breast cancer, differentiation, morphometryIn a leading article in Lancet 1960 (3) the author concludes that "pathetically little is known about the biophysical bases of (cell) adhesion." Although knowledge has increased the last 20 years, there are still many unclear factors involved in elucidating how cells adhere to one another. Local invasion of cancer has been claimed to depend on the cohesiveness of tumor cells (5). Not only are cancer cells less cohesive than normal cells but also there seems to be variability in the tion of the tumor border to the surrounding fat (9). It is confusing that differentiation is considered together with these factors since it is not known to what extent they contribute independently to the prognostic outcome. This is further underlined in a recent truncated component analysis (17) showing that they do not seem to describe the same biologic phenomenon. In addition, in one study (4) only one expression of differentiation-tubule formation is evaluated, cohesiveness of cell populations of different tumors obtained from the same organ. In fine-needle biopsies from breast cancer this is reflected in varying degrees of dissociation of tumor cells. The smaller the clusters, the less differentiated the tumor is thought to be. In addition, in a study of the prognostic value of the aspiration biopsy smears using AIDanalysis, Wallgren and Zajicek (19) noted that the cluster size (more than or less than 10 cells/cluster) was significant in predicting 10-year survival.In some studies of prognostic factors in breast cancer various histopathologic expressions of degree of differentiation are correlated with 5-year survival or 3-year recurrence rate (4, 9, 15)' although differentiation in most of these studies is evaluated in combination with other factors-nuclear atypia, frequency of mitoses or hyperchromatic nuclei (4, 14) or degree of lymphocytic infiltration in the tumor and the rela-I Supported by NIH/NCI Contract NOlCB53968. 'Stenkvist B, Bengtsson E, Eriksson 0, Nordin B, Jarkrans T, Westman-Naeser S: Submitted for publication.an unexplained restriction, since acinus, lobule or duct formation also determine differentiation.We have recently published a study of computerized nuclear morphometry of cell nuclei from breast cancer (16). In looking for a method to quantitate morphometrically the degree of differentiation of cancer we tried a particle suing experiment described in this study. Material and MethodsThe material analyzed in this study was part of a study of 179 wome...

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“…A lot of investigations have been carried out using the nuclear grading system proposed by Black & Speer (1957) or using other nuclear parameters such as nuclear crowding and lobulation (Stenkvist et al, 1979). Their major drawbacks seem to be their lack of reproducibility and their subjectivity (Freedman et al, 1979;Stenkvist et al, 1979).…”

Section: Discussionmentioning

confidence: 99%

“…In a previous report (van Bogaert & de Muylder, 1980) we showed that tissue fixation and processing modify nuclear diameters; hence a comparison with cytological data is feasible only after correction by a factor of 1-55. The present study was carried out to verify in tissue sections a possible link between 3 categories of nuclear size and early prognosis.…”

mentioning

confidence: 99%

Prognostic implications of mean nuclear diameter in breast cancer

Bogaert¹,

Muylder²,

Maldague³

et al. 1980

Br J Cancer

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Summary.-The mean nuclear diameter of 100 breast cancers was measured on tissue sections, to evaluate its importance for early prognosis. The cases were subdivided into 3 subgroups: small (25.5% of cases), medium (63.3%) and large (112%) nuclei. Early recurrence and mortality rates were investigated in each of the categories. Increasing nuclear size was shown to be related to mortality from metastatic disease. However, large-nucleus tumours had an inverse relationship with lymphnode involvement and possibly with recurrence rate. Hence, in our material nuclear size as a sole criterion was not a good indicator of the early behaviour of operable breast cancer.

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Analysis of reproducibility of subjective grading systems for breast carcinoma.

Cited by 130 publications

References 9 publications

Assessment of milk fat globule membrane antibodies and lectins as markers of short-term prognosis in breast cancer

Assessment of milk fat globule membrane antibodies and lectins as markers of short-term prognosis in breast cancer

A morphometric expression of differentiation in fine‐needle biopsies of breast cancer

Prognostic implications of mean nuclear diameter in breast cancer

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