The multi-center morphometric mammary carcinoma project (MMMCP) in the netherlands: Value of morphometrically assessed proliferation and differentiation

Baak, J. P. A.; Diest, Paul J. van; Benraadt, T.; Matze-Cok, E.; Brugghe, J.; Schuurmans, L. T.; Littooy, J. J.

doi:10.1002/jcb.240531141

Cited by 21 publications

(11 citation statements)

References 23 publications

(1 reference statement)

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“…Also, less frequent aberrations such as gains of 7q and l7q and losses of 11q, 13q, and 17p are consistent with other studies 5, 8, 18, 19. In agreement with other studies, MAI is the strongest independent morphological prognosticator in the current lymph node‐negative breast cancers (Figure 3) 1, 2, 20. Correlation between the MAI and specific chromosomal aberrations could thus provide us with a better insight into the underlying genetic mechanism and perhaps also point to a new prognostic genetic marker.…”

Section: Discussionsupporting

confidence: 91%

“…A combination of tumour size, grade, and oestrogen receptor is often used for this purpose (St Gallen criterion). In addition, proliferation markers such as the mitotic activity index (MAI) and S‐phase are strong prognostic factors exceeding histological grade, as many independent studies have shown 1–3. Alterations in the genetic make‐up of tumour cells are at the basis of these phenotypic characteristics and the biological behaviour of a tumour.…”

Section: Introductionmentioning

confidence: 99%

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In lymph node‐negative invasive breast carcinomas, specific chromosomal aberrations are strongly associated with high mitotic activity and predict outcome more accurately than grade, tumour diameter, and oestrogen receptor

Janssen¹,

Baak

Guervós

et al. 2003

The Journal of Pathology

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The objectives of this study were to analyse whether specific chromosomal gains and losses in lymph node-negative breast cancer correlate with other features and to evaluate their prognostic value. Seventy-six lymph node-negative breast carcinomas (median follow-up 46 months; range 9-105 months) were used. Histological grade, tumour type, maximal tumour diameter, oestrogen/progesterone receptor (ER/PR), mitotic activity index (MAI), and mean nuclear area (MNA) were assessed. Whole genome DNA analysis was performed by comparative genomic hybridization (CGH). Chromosomal aberrations were compared with classical and other prognostic features. Kaplan-Meier curves and multivariate survival analysis (Cox model) were used to assess the prognostic value of the CGH and other data. Fifteen (21.4%) out of 70 patients (six cases were lost to follow-up) developed locoregional (n=3) or distant metastases (n=12). The following criteria were prognostic for (any) recurrence (in decreasing significance): 3q gain, simultaneous gain at 1q and 8q, MAI < versus > or =10, MNA < versus > or =63 microm. Loss of 1p occurred significantly more often in the large group of ductal breast carcinomas with a MAI > or =10 (n=38) than in cancers with a MAI<10. Moreover, 8/15 (53%) patients with recurrences had a gain at 3q, as opposed to three (5.5%) of the 55 recurrence-free patients. This association was even stronger in ductal carcinomas (hazard ratio=10.9, p<0.0001). Cox regression revealed that the 3q gain was the strongest prognostic factor; other features did not have additional prognostic value. In conclusion, loss of 1p is associated with a high MAI. A gain of 3q is a stronger predictor of recurrence than grade, MAI, and other features in invasive breast cancers.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

In lymph node‐negative invasive breast carcinomas, specific chromosomal aberrations are strongly associated with high mitotic activity and predict outcome more accurately than grade, tumour diameter, and oestrogen receptor

Janssen¹,

Baak

Guervós

et al. 2003

The Journal of Pathology

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“…It had a restricted value in the premenopausal patients. On the other hand, MNA was useful in the premenopausal patients in European based studies (Baak et al,1993;.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Morphometry in African Breast Cancer

Ikpatt¹,

Kuopio

Collan³

2011

Image Anal Stereol

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Three hundred cases of invasive breast cancer diagnosed between 1983 and 1999 in Calabar, Nigeria were analysed to determine the nuclear morphometric variables, and evaluate the prognostic potential of nuclear morphometry in Nigerian breast cancers. The necessary follow-up was available for 129 patients. The nuclear area was the most valuable variable. In the Nigerian material, the mean nuclear area (MNA) (SD) was 89.2 (34.0) µm 2 . MNA was significantly higher in tumours of the postmenopausal than premenopausal (p = 0.0405), in LN+ than LN-(p = 0.0202) patients, and in tumours over 3 cm than smaller ones (p < 0.0001). There were also significant differences between different clinical stages, histological grades, and histological types of tumours. Significant correlations were observed between MNA and histological grade (r = 0.64), standard mitotic index (r = 0.45) and tumour size (r = 0.20). MNA as a continuous variable was a statistically significant prognosticator in the whole material (p = 0.0281), and among the postmenopausal patients (p = 0.0238). Univariate cox´s regression demonstrated one significant grading cutpoint at MNA = 111 µm 2 , which divided the material into two groups of different survival. The development of a morphometric grading system optimal for the Nigerian material could use the latter cut-point between nuclear scores 2 and 3 in the grading system. The earlier proven cut-point of 47 µm 2 could be used between nuclear scores 1 and 2.

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“…Although the numbers of apoptotic 26 and mitotic cells 15,27 are strong prognosticators for invasive breast cancer and also seem to be important in ductal CIS, 28 they did not appear to be useful for predicting breast cancer development in patients with a normal or hyperplastic breast biopsy. This is a disappointment, as it seems logical that proliferation and apoptosis (and especially the balance between these processes) would be critical for progression toward malignancy.…”

Section: Resultsmentioning

confidence: 99%

Prognostic value of morphometry in patients with normal breast tissue or usual ductal hyperplasia of the breast

Mommers¹,

Page²,

Dupont³

et al. 2001

Int. J. Cancer

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Women with usual ductal hyperplasia have a relative risk of 1.6-1.9 of subsequent breast cancer development. This slightly increased risk is generally not considered sufficiently high to justify (chemo)preventive therapy. It is therefore important to identify high-risk ductal hyperplastic lesions that would benefit from such a treatment. Nuclear morphometric features have been shown in previous work to be useful for objectively describing morphologic features associated with high risk in (pre)invasive breast lesions. The aim of this study was to evaluate whether such morphometric features can also predict subsequent invasive cancer development in patients with the common pattern of usual ductal hyperplasia or a normal breast biopsy. The present case-control study included 423 women with normal breast biopsies (n = 89) or biopsies containing usual ductal hyperplasia (n = 334). Of these 423 women, 132 developed invasive breast cancer during follow-up (mean 16.7 +/- 7.0 years). On the original hematoxylin and eosin-stained sections, nuclear morphometry was performed with a digitizing video overlay system, and mitotic and apoptotic indices were assessed. Patients with mean nuclear feature values for area, perimeter, diameter or longest axis above the 75th percentile had 1.6-1.7 times the breast cancer risk of women with mean nuclear feature values below this value. Pairwise combinations of these features yielded slightly higher cancer risks for the fourth quartile patients, with the highest risk (1.9) for patients with SD of nuclear area and perimeter values above the 75th percentile. The number of apoptotic or mitotic cells had no prognostic value for patients with apparently normal tissue or usual ductal hyperplasia. Our results give a first indication that normal breast tissue or usual ductal hyperplasia harbor nuclear morphologic changes that, when assessed by morphometry, may be used to predict breast cancer development. It is worthwhile studying this further in independent groups of patients with long-term follow-up.

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The multi-center morphometric mammary carcinoma project (MMMCP) in the netherlands: Value of morphometrically assessed proliferation and differentiation

Cited by 21 publications

References 23 publications

In lymph node‐negative invasive breast carcinomas, specific chromosomal aberrations are strongly associated with high mitotic activity and predict outcome more accurately than grade, tumour diameter, and oestrogen receptor

In lymph node‐negative invasive breast carcinomas, specific chromosomal aberrations are strongly associated with high mitotic activity and predict outcome more accurately than grade, tumour diameter, and oestrogen receptor

Nuclear Morphometry in African Breast Cancer

Prognostic value of morphometry in patients with normal breast tissue or usual ductal hyperplasia of the breast

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