Biomedical subjects

E C Wisse-Brekelmans

Publications and source records attributed to E C Wisse-Brekelmans.

9 recordsLinked to original sources

PubMed1992

Regional differences in breast cancer survival are correlated with differences in differentiation and rate of proliferation.

Patients with invasive ductal breast cancer and with 5 to 12 years of follow-up, identified from two pathology laboratories serving hospitals in two distinct but fairly close regions, were studied for differences in length of survival. In the years when the cases were diagnosed, population screening was not performed, adjuvant systemic therapy was not administered, and surgical treatment and irradiation protocols were similar in the hospitals served by the two laboratories. There was a significant difference in length of survival between the two regional groups (N1 = 160, N2 = 111; P = .006). Survival rate at 10 years in the two regions was 48% and 69%. Distribution of age, tumor size, and lymph node status (as negative or positive as well as number of positive nodes) were similar, but quantitative and qualitative microscopic features differed. Patients from the region in which the prognosis was less favorable had the higher median values for the mitotic activity index (14 v 4; P less than .0001) and for nuclear area (59.2 v 38.2; P less than .0001). Nuclear and histologic grade distributions were also different between the regions. Logistic regression analysis confirmed that the regional survival differences are correlated with the microscopic features, even after adjustment for age, tumor size, and lymph node status. Comparison of breast cancers from the periods 1970 to 1974 and 1988 to 1989 in one of the two regions revealed that the clinical and microscopic proliferation features were similar over time. These results, apart from indicating regional variation in breast cancer survival rate correlated to differences in the microscopic characteristics of the disease between regions, provide additional support to previous reports that qualitative and, especially, quantitative microscopic differentiation and proliferation features have significant bearing on the prognosis of breast cancer patients.

Breast Neoplasms↗

PubMed1992

Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the Multicenter Morphometric Mammary Carcinoma Project.

The Multicenter Morphometric Mammary Carcinoma Project is a prospective study on the reproducibility and prognostic value of routine quantitative assessments, especially the mitotic activity index (MAI), the multivariate prognostic index (MPI; a combination of MAI, tumor size, and lymph node status), the mean nuclear area, and DNA ploidy assessments in patients with invasive breast cancer. Fourteen pathology laboratories providing routine services to 35 hospitals throughout The Netherlands are participating in this project. In this article, the reproducibility of MAI and MPI assessments is described. Assessment of the MAI was, according to a strict protocol, first performed in the participating laboratories; thereafter, slides were transferred to the coordination center in Amsterdam for quality control. Analysis of the reproducibility of the assessments in 2,469 patients showed correlation coefficients between 0.81 and 0.96 (mean, 0.91) for the MAI and between 0.91 and 0.97 (mean, 0.96) for the MPI. The reproducibility was fairly constant in time, although it showed a slight drop in the middle of the 2-year intake period. A prognostically relevant discrepancy in MPI (caused by differences in MAI) between the original and quality control assessments was found in only 7.2% of the cases. When analyzing the reasons for these discrepancies, a plausible explanation could be found in all cases: bad tissue processing and ignorance of or negligence in following the protocol guidelines for selection of the counting area or in the process of counting were the most important flaws. Since these errors are largely controllable, an even lower discrepancy rate is theoretically achievable. In conclusion, in a routine setting it can be learned, within a reasonable time, to perform mitosis counting in a highly reproducible way if a strict protocol is carefully followed. This opens the way for a wider application of the MAI and MPI in breast cancer patients. Motivation is, however, an important factor to obtain reproducible results, and ongoing quality control is essential to guarantee the reproducibility of the assessments.

Breast Neoplasms↗

PubMed1992

Assessment of the risk on endometrial cancer in hyperplasia, by means of morphological and morphometrical features.

The value of two "cancer risk" assessment rules (one consisting of qualitative microscopical features and one consisting of morphometric characteristics) has been evaluated in 39 patients with hyperplasia of the endometrium. Of these, in seven (7139 = 18%) cancer was detected in the follow-up and 32 remained stable or became less abnormal. The results of the qualitative analysis were well in agreement with those published earlier. In none of the eight patients with simple hyperplasia cancer was detected, in contrast to five of the 11 patients (45%) with cytologic atypia and glandular complexity. Twenty patients showed cytologic atypicality in the absence of glandular complexity, or no atypicality but glandular complexity; in two (10%) of these patients cancer was detected later in the follow-up. The morphometric rule (consisting of volume percentage of stroma, log-normally transformed standard deviation of the shortest nuclear axis and outer surface density of the glands) results in a multivariate score. Nineteen patients had a score value above 0.6 and in none of them cancer was found. In contrast, in seven of the 20 patients (35%) with a score value below 0.6, cancer was detected. Regarding the question which of the techniques is more powerful, the specificity is better with the qualitative evaluations; the sensitivity is higher with the morphometric rule. An advantage of the morphometric rule is that only two groups (very low/very high risk) are discerned.

Endometrial Hyperplasia↗

PubMed1989

The percentage of aneuploid cells is significantly correlated with survival in accurately staged patients with stage 1 resected squamous cell lung cancer and long-term follow up.

Previous studies have shown that ploidy is an important prognostic determinant in lung cancer, but in those studies followup was restricted to three years, while patients with Stage 1, 2 and 3 disease and with different histological subtypes were included. Theoretically, these factors could have influenced the findings, especially since aneuploidy strongly correlated with the stage of disease. Because of this, tumor ploidy was studied in surgically resected stage 1 (T1/2, N0M0) squamous cell lung cancer patients with a minimal followup of 6 years. All patients were accurately staged by mediastinal lymph node mapping. Fifty-two from a group of 1539 patients with lung cancer diagnosed between 1980 and 1986 inclusive, fulfilled these criteria. Of these tumors, 23 (44%) were diploid with a 6-year survival of 53% and 29 (56%) were aneuploid with a 6-year survival of 48%. Although diploidy tended to be associated with local relapse of the tumor and aneuploidy with distant metastases, the difference was not significant and neither showed a survival advantage. However, within the aneuploid tumors, there was a significant correlation between the percentage of aneuploid cells and survival, defined as event-free or time to death. Seventeen patients with a percentage of more than 10 had a worse outcome (12 died, 6 years survival 35%), than to the other 12 patients with less than 10% aneuploid cells (2 died, 6-year survival 78%) (Mantel-Cox = 6.04, P = 0.01). This implies that in patients with accurately staged and histologically proven Stage 1 squamous cell lung cancer and long-term follow up, DNA content classified as diploid and aneuploid is not a prognostic factor for survival, but the percentage of aneuploid tumor cells is correlated with the prognosis.

Aged↗

PubMed1989

Data processing and analysis in the Multicenter Morphometric Mammary Carcinoma Project (MMMCP).

In the Multicenter Morphometric Mammary Carcinoma Project (MMMCP), the prognostic value and reproducibility of routinely assessed quantitative pathological parameters in breast cancer is prospectively studied in approximately 3000 patients. Considering the high number of patients and the fact that many laboratories and hospitals throughout the Netherlands participate in this project, data acquisition, processing and analysis is an important component of the project. The data collection scheme, the structure of the database and the processing of data are described.

Breast Neoplasms↗

PubMed1988

Architectural and nuclear morphometrical features together are more important prognosticators in endometrial hyperplasias than nuclear morphometrical features alone.

Previous studies have shown that 80-90 per cent of cases of atypical hyperplasia of the endometrium do not progress to cancer. Criteria to predict the outcome in an individual patient with hyperplasia are lacking, and hysterectomy is the usual (over)treatment in order to avoid a 10-20 per cent chance of confrontation with cancer later on in the course of the disease. A recent study has shown that using a nuclear morphometric classification rule, 15 per cent of patients without progression can be accurately separated from patients with progression. However, as it is unlikely that nuclear morphometrical features are the only morphological factors reflecting the outcome of the disease, other quantitative parameters describing the architecture of the glands have also been studied for their potential value in selecting patients who will progress to cancer. In total, 10 nuclear features and 12 glandular architectural features were studied in 39 cases of atypical endometrial hyperplasia. Among these cases, seven (18 per cent) progressed to cancer. Using linear stepwise regression analysis and discriminant analysis, the volume percentage stroma and the standard deviation of the shortest nuclear axis are the best discriminators, although the outer surface density of the glands also adds to the discriminating power. The volume percentage stroma is the best single prognosticator; this feature is highly reproducible. In total, using these combined architectural and nuclear morphometrical features, 20 of the 32 cases without progression were separated from those who subsequently progressed (62.5 per cent). This is a considerable improvement over nuclear morphometrical features alone (15 per cent separated).

Cell Nucleus↗

PubMed1988

The prognostic value of morphometrical features and cellular DNA content in cis-platin treated late ovarian cancer patients.

In 73 CAP-1 treated stage III and IV ovarian cancers, the prognostic significance of morphometric features and cellular DNA content has been evaluated in comparison with histologic type, grade of differentiation and a number of clinical characteristics. Borderline tumours were excluded from the study. Median follow-up was 44 months, median survival time 36 months. Single features associated with prognosis were (in order of decreasing significance according to single variate analysis): FIGO stage (P = 0.0002), bulky disease (P = 0.004), standard deviation and mean of nuclear area (P = 0.0006 and P = 0.01), cellular DNA content (P = 0.01), mitotic activity index (P = 0.08) and volume percentage epithelium (P = 0.13, not quite significant). Tumours with a mean nuclear area greater than 70 micron2 (which occurred in 35% of the cases) were nearly all aneuploid. Multivariate analysis showed that the statistically most significant prognostic combination of features consisted of mean nuclear area, presence or absence of bulky disease and FIGO stage (in order of decreasing importance) (Mantel-Cox = 23.07, P less than 0.00001). A low value for the multivariate function of this combination of features was associated with a poor prognosis within 24 months, a high value with a favourable outcome. Another favourable combination of features appeared to be diploid cellular DNA content and a low mitotic activity index (11 patients, one died). However, even with the prognostically most favourable combination of these features, several patients died. Of all combinations of features investigated, only two were associated with an excellent prognosis (low mitotic activity index and low volume percentage epithelium). Cancers of 7 patients (10%) displayed such features, and none of them died during the follow-up period (minimally 20 and maximally 54 months). It is concluded that morphometric and flow cytometric analysis can provide significant and objective information to predict the prognosis of cis-platin-treated advanced ovarian cancer patients.

Adult↗

PubMed1987

Evaluation of the prognostic value of morphometric features and cellular DNA content in FIGO I ovarian cancer patients.

Approximately 20% to 40% of the patients with a FIGO I ovarian tumor die within five years after the diagnosis. Morphologic studies (typing and grading) of the primary tumor are prognostically important, but poorly reproducible. Therefore, the prognostic value of more objective techniques, such as morphometry and flow cytometric (FCM) DNA determinations, were evaluated in 33 adequately staged FIGO I patients with at least a five-year follow-up. The overall five-year survival in the group was 64%. Three patient categories were defined on the basis of two easily measured morphometric features, the mitotic activity index (MAI) and the volume percentage epithelium (VPE), which an earlier study had proved to be significantly associated with prognosis. The five-year survival rates were 91% for 11 patients in category A (MAI less than 30 and VPE less than 65), 67% for 9 patients in category B (MAI less than 30 and VPE greater than or equal to 65) and 38% for 13 patients in category C (MAI greater than or equal to 30). FCM showed 25 of the tumors to be diploid and 8 to be aneuploid. The cellular DNA content was also of prognostic value: the five-year survival figures for patients with diploid and aneuploid tumors were 68% and 37%, respectively. Combination of the morphometric and FCM features showed that, in diploid tumors, the morphometric features have additional prognostic value: the diploid-tumor-patient survival rates in categories A, B and C were 91%, 63% and 50%, respectively. None of the eight patients with aneuploid tumors fell in the morphometrically favorable category A while seven were in category C.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗

PubMed1986

Morphometric data to FIGO stage and histological type and grade for prognosis of ovarian tumours.

The prognostic value of using histological typing, grading, and morphology, in addition to clinical staging, was assessed in 98 cases of invasive ovarian cancer of the common epithelial types (serous, mucinous, and endometrial). All of these cases had at least five years of follow up. When regression analysis was used, the International Federation of Gynaecology and Obstetrics' (FIGO) staging system was the best indicator for prognosis. Analysis of a combination of morphometric features was the second best indicator, being especially useful for the those patients with stage I disease. Variables that indicated a relatively poor prognostic outcome were mitotic index above 30; volume percentage epithelium above 65%; shortest nuclear axis above a mean of 1 X 1 micrometers. Histological typing of ovarian tumours was of limited value; mucinous tumours have a somewhat better prognosis than serous tumours, but the prognostic value of typing alone was found to be limited. Qualitative histological grading was useful, but the prognostic value of morphometric grading was better. Measurement of morphological features with an interactive computer program is simple and can be done by a pathologist or a technician: in future it is likely that such automated systems of measurement will improve the objectivity of tissue analysis.

Cell Nucleus↗