Ductal carcinoma in situ of the breast: a new phenotype classification system and its relation to prognosis.
ABSTRACT In a study of invasive breast cancer, multiple correspondence analysis (MCA) revealed clustering of eight pathobiological variables. Two different phenotypes were distinguished by an index calculated on the basis of the variables (histologic grade, necrosis, lymphoid infiltration, number of mitosis and expression of c-erbB-2, p53, progesterone receptor and Bcl-2). Phenotype A lesions share most of the features of normal breast tissue. Phenotype B looks more malignant, has a higher early recurrence rate and is more frequently seen in younger patients. Our aim was to see if ductal breast carcinoma in situ (DCIS) could be divided into the same phenotypes. One hundred and eighty DCIS were investigated. Association between the eight variables was studied in 2 x 2 models. The phenotype index was calculated by summing weights for the variables in the MCA. All variables were associated, except Bcl-2. DCIS was divided in two phenotypes. Thirty-three tumours were Phenotype A and 147 Phenotype B. The mean age at diagnosis was 65.5 and 58.4 years for Phenotypes A and B, respectively (p = 0.0012). No difference regarding local relapse free survival was seen. Two phenotypes were distinguished in DCIS, similar to invasive breast cancer. In an earlier study, 45% of the invasive cancers were classified as Phenotype B. In this study, 82% of DCIS were Phenotype B. This may indicate that invasive breast cancer of Phenotype B is derived from DCIS of Phenotype B. The distribution of DCIS phenotypes with a small proportion of Phenotype A DCIS may be due to that Phenotype A DCIS is less likely to be detected by mammography, or that some invasive breast cancers of Phenotype A progress to invasiveness without passing the in situ phase.
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ABSTRACT: OBJECTIVES: The aim of the present study was to evaluate the nuclear grade, the expressions of p53 and c-erbB-2 proteins, and the estrogen receptors (ER) of 38 women with ductal carcinoma in situ (DCIS) and invasive carcinoma of the same breast. METHODS: the protein profile of 38 women was investigated in a descriptive and retrospective study, through the immune-histochemical technique. The cut-off limit for positive staining was chosen at 10% or more of positive cells for p53 and c-erbB-2 proteins and for ER. The analysis of the concordance between the expressions of proteins and the nuclear grade was done by the kappa coefficient, according to Landis and Koch's criteria. MacNemar's test was used to assess the differences between the two groups. RESULTS: there was a perfect concordance in the expression of p53 proteins (kappa coefficient = 1.00) and almost a perfect concordance for c-erbB-2 proteins, ER and nuclear grade (kappa coefficients = 0.84, 0.89 and 0.89) between in situ and invasive elements of the same tumor. CONCLUSION: there was no difference between the expressions of p53 and c-erbB-2 proteins, ER and nuclear grade in the DCIS and invasive carcinoma of the same breast.Revista Brasileira de Ginecologia e Obstetrícia 07/2004; 26(6):435-439.
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ABSTRACT: Nuclear grade of breast DCIS is considered during patient management decision-making although it may have only a modest prognostic association with therapeutic outcome. We hypothesized that visual inspection may miss substantive differences in nuclei classified as having the same nuclear grade. To test this hypothesis, we measured subvisual nuclear features by quantitative image cytometry for nuclei with the same grade, and tested for statistical differences in these features. EXPERIMENTAL DESIGN AND STATISTICAL ANALYSIS: Thirty-nine nuclear digital image features of about 100 nuclei were measured in digital images of H&E stained slides of 81 breast biopsy specimens. One field with at least 5 ducts was evaluated for each patient. We compared features of nuclei with the same grade in multiple ducts of the same patient with ANOVA (or Welch test), and compared features of nuclei with the same grade in two ducts of different patients using 2-sided t-tests (P ≤ 0.05). Also, we compared image features for nuclei in patients with single grade to those with the same grade in patients with multiple grades using t-tests. Statistically significant differences were detected in nuclear features between ducts with the same nuclear grade, both in different ducts of the same patient, and between ducts in different patients with DCIS of more than one grade. Nuclei in ducts visually described as having the same nuclear grade had significantly different subvisual digital image features. These subvisual differences may be considered additional manifestations of heterogeneity over and above differences that can be observed microscopically. This heterogeneity may explain the inconsistency of nuclear grading as a prognostic factor.Cancer informatics 01/2010; 9:209-16.
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ABSTRACT: Das duktale Carcinoma in situ (DCIS) ist eine heterogene Erkrankung mit einem Progressionsrisiko von etwa 30–50%. Unsere Kenntnisse ber den natrlichen Verlauf der Erkrankung sind begrenzt, sodass es derzeit nicht mglich ist, individuell vorherzusagen, ob ein DCIS zu einem invasiven Karzinom fortschreiten wird oder nicht. Trotz dieser Einschrnkung bilden heute pathomorphologische Parameter die wesentliche Grundlage fr die Abschtzung der Prognose und Therapieplanung. Der Ausschluss eines invasiven Mammakarzinoms, die Bestimmung von Kerngrad, Architektur, Gre und Verteilungsmuster des DCIS sowie der Nachweis von Nekrosen und die Erhebung des Resektionsrandstatus einschlielich der Sicherheitsabstnde sind entscheidend fr das lokale Vorgehen. Die Bestimmung des Hormonrezeptorstatus ist bei Patientinnen angezeigt, bei denen eine Tamoxifenbehandlung nach brusterhaltender Therapie erwogen wird. Dabei empfiehlt sich die sorgfltige Beurteilung der genannten Parameter in Anlehnung an international akzeptierte Vorgaben, deren prognostische Relevanz und diagnostische Reproduzierbarkeit belegt ist. Dennoch sind bessere Prognosemarker erforderlich, um Patientinnen mit dieser zunehmend hufiger diagnostizierten Erkrankung zuknftig eine individuell angepasste Behandlung anbieten zu knnen.Ductal carcinoma in situ (DCIS) is a heterogeneous disease that progresses to invasive cancer in 30–50% of the patients. Its natural history is poorly defined so that we are unable to identify cases of DCIS that do not progress to invasive carcinoma during an individuals lifetime. However, pathologic features of DCIS are nowadays the basis for the estimation of the prognosis and planning of therapy. Exclusion of microinvasion, characterization of nuclear grade, architecture, size and distribution of the DCIS, presence or absence of comedonecrosis as well as the assessment of surgical margins are relevant factors for local treatment. The determination of steroid hormone receptor status is indicated in patients considering tamoxifen therapy after breast conservation. It is advisable to evaluate the features according to internationally accepted guidelines with proven prognostic relevance and reproducibility. Nevertheless, better prognostic factors are needed to adapt the management of this increasingly diagnosed disease to the individual patient.Der Pathologe 08/2006; 27(5):326-336. · 0.62 Impact Factor