Tumour markers in breast carcinoma correlate with grade rather than with invasiveness

Department of Surgery, University Hospital Uppsala, S-751 85 Uppsala, Sweden.
British Journal of Cancer (Impact Factor: 4.84). 10/2001; 85(6):869-74. DOI: 10.1054/bjoc.2001.1995
Source: PubMed


Ductal breast carcinoma in situ (DCIS) is regarded as a precursor to invasive breast cancer. The progression from in situ to invasive cancer is however little understood. We compared some tumour markers in invasive and in situ breast carcinomas trying to find steps in this progression. We designed a semi-experimental setting and compared histopathological grading and tumour marker expression in pure DCIS (n = 194), small invasive lesions (n = 127) and lesions with both an invasive and in situ component (n = 305). Grading was done according to the Elston-Ellis and EORTC classification systems, respectively. Immunohistochemical staining was conducted for p53, c-erbB-2, Ki-67, ER, PR, bcl-2 and angiogenesis. All markers correlated with grade rather than with invasiveness. No marker was clearly associated with the progression from in situ to invasiveness. The expression of tumour markers was almost identical in the 2 components of mixed lesions. DCIS as a group showed a more 'malignant picture' than invasive cancer according to the markers, probably, due to a higher proportion of poorly differentiated lesions. The step between in situ and invasive cancer seems to occur independently of tumour grade. The results suggest that well-differentiated DCIS progress to well-differentiated invasive cancer and poorly differentiated DCIS progress to poorly differentiated invasive cancer.

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    • "Between 14 and 50% of DCIS lesions are estimated to progress to invasive lesions if left untreated [20]. To date, neither the histopathological classification nor the conventional biomarkers can accurately predict whether DCIS lesions can invade the surrounding tissue and consequently progress to metastatic disease [21]. Many efforts have been made to properly classify the risk of progression of DCIS using morphological and molecular features. "
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    ABSTRACT: The spread of mammographic screening programs around the world, including in developing countries, has substantially contributed to the diagnosis of small non-palpable lesions, which has increased the detection rate of ductal carcinoma in situ (DCIS). DCIS is heterogeneous in several ways, such as its clinical presentation, morphology and genomic profile. Excellent outcomes have been reported; however, many questions remain unanswered. For example, which patients groups are over-treated and could instead benefit from minimal intervention and which patient groups require a more traditional multidisciplinary approach. The development of a comprehensive integrated analysis that includes the radiological, morphological and genetic aspects of DCIS is necessary to answer these questions. This review focuses on discussing the significant findings about the morphological and molecular features of DCIS and its progression that have helped to uncover the biological and genetic heterogeneity of this disease. The knowledge gained in recent years might allow the development of tailored clinical management for women with DCIS in the future.
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    • "The identification of markers that can predict recurrence and/or invasion in DCIS is critical. Some studies have showed that expression of ER, PR, HER2, Ki67, and p53 correlate with tumor grade rather than invasion [1] [2] [3] [4] [5]. "
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    ABSTRACT: There is a paucity of data regarding molecular subtypes of pure ductal carcinoma in situ (pDCIS). We evaluated the expression of ER, PR, HER2, Ki67, and p53 and DNA ploidy in 118 pDCIS and 100 invasive breast carcinomas (IBCAs) by routine IHC and classified them according to molecular subtypes. Quantification of biomarkers and DNA ploidy was performed by image analysis. Expression of ER, PR, and high ki67 was more frequent in pDCIS compared to IBCA. High-grade tumors had lower ER and PR expression, high Ki67, overexpression of HER2 and p53, and DNA aneuploidy. Luminal A and HER2 subtypes were more common in pDCIS, and triple negative was more prevalent in IBCA. In both groups, HER2 and triple negative subtypes were characterized by high ki67, overexpression of p53, and DNA aneuploidy compared to luminal subtypes. Molecular subtypes of IBCA are distinct from those of pDCIS. Invasion is characterized by change in phenotype in some tumors.
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    • "Gene expression data from 115 tumours of the same cohort were used for in silico validation of expression levels and 38 of these were validated by qRT-PCR. Methylation analysis was performed on 86 tumours from a cohort of early lesions of breast cancer, 27 pure DCIS, 27 pure invasive (< 15 mm) and 32 mixed lesions (invasive with in situ component) [13] and in 75 DNA tumour samples from patients with locally advanced breast cancer (T3/T4) [14]. Microarray data of RIC8A were further in silico validated in 251 primary breast tumours [6]. "
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