The mammographic correlations of a new immunohistochemical classification of invasive breast cancer (original) (raw)
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Intratumoral Heterogeneity of Immunohistochemical Marker Expression in Breast Carcinoma
Applied Immunohistochemistry & Molecular Morphology, 2010
Core needle biopsies of breast carcinomas provide diagnostic, prognostic, and predictive information before neoadjuvant therapy. Possible intratumoral heterogeneity of biomarker expression questions the validity of core needle biopsy interpretation in small biopsy specimens. Using tissue microarray (TMA) technology, we studied intratumoral heterogeneity of 7 immunomarkers. Five TMAs were constructed from 44 breast carcinomas and 5 normal breast tissues, each represented by 1-mm cores in triplicate from each of 3 foci. TMAs were immunostained for monoclonal estrogen receptor (ER), monoclonal progesterone receptor (PR), polyclonal human epidermal growth factor receptor 2 (HER2), monoclonal E-cadherin (E-cad), monoclonal epidermal growth factor receptor (EGFR), monoclonal p53, and monoclonal MIB-1. Expression was quantified visually by light microscopy and by image cytometry as intensity, percentage of cells positive, and score. Using intraclass correlation coefficient, heterogeneity in the expression of the immunomarkers within subjects was compared with the overall variance. Intratumoral heterogeneity was seen with 5 immunomarkers: ER, PR, HER2, p53, and MIB-1. E-cad and EGFR failed to show intratumoral heterogeneity. Intratumoral heterogeneity in ER, PR, HER2, p53, and MIB-1 indicates their problematic interpretation in small biopsy specimens as indicative of the status of the entire tumor. A negative result does not exclude the expression of these markers in the remainder of the tumor. E-cad (positive in ductal carcinomas) and EGFR lacked heterogeneity. *High (>0.75) is equivalent to no heterogeneity; low (r0.75) is equivalent to heterogeneity. EGFR indicates epidermal growth factor receptor; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor.
British journal of cancer, 1991
Features of 111 mammary carcinomas derived from breast cancer screening were compared with those of 69 carcinomas presenting 'clinically'. Screen detected cancers were smaller, had less likelihood of nodal metastases, included a higher proportion of in situ tumours and if invasive, tended to be of lower grade. Using immunohistochemical methods, the expression of c-erbB-2 oncoprotein, epidermal growth factor receptor (EGFR) and cathepsin D were compared in the two groups. A similar proportion of screened and unscreened tumours expressed c-erbB-2 oncoprotein and EGFR but expression of the oestrogen regulated protein cathepsin D was significantly more frequent in the screened group (P less than 0.05). Although a relatively small series, the results suggest a biological difference between 'screened' and 'clinical' tumours.
BMC Cancer, 2010
Background: Breast cancer is not a single entity but a diverse group of entities. Advances in gene expression profiling and immunohistochemistry as its surrogate marker have led to the unmasking of new breast cancer molecular subtypes, resulting in the emergence of more elaborate classification systems that are therapeutically and prognostically more predictive. Molecular class distribution across various ethnic groups may also reveal variations that can lead to different clinical outcomes in different populations. Methods: We aimed to analyze the spectrum of molecular subtypes present in the Saudi population. ER, PR, HER2, EGFR and CK5/6 were used as surrogate markers for gene expression profiling to classify 231 breast cancer specimens. Correlation of each molecular class with Ki-67 proliferation index, p53 mutation status, histologic type and grade of the tumor was also carried out. Results: Out of 231 cases 9 (3.9%) were classified as luminal A (strong ER +ve, PR +ve or-ve), 37 (16%) as luminal B (weak to moderate ER +ve, and/or PR +ve), 40 (17.3%) as HER2+ (strong or moderately positive HER 2 with confirmation by silver enhanced in-situ hybridization) and 23 (10%) as basal (CK5/6 or EGFR +ve). Co-positivity of different markers in varied patterns was seen in 23 (10%) of cases which were grouped into a hybrid category comprising luminal B-HER2, HER2-basal and luminal-basal hybrids. Ninety nine (42.8%) of the tumors were negative for all five immunohistochemical markers and were labelled as unclassified (penta negative). A high Ki-67 proliferation index was seen in basal (p = 0.007) followed by HER2+ class. Overexpression of p53 was predominantly seen in HER2 + (p = 0.001) followed by the basal group of tumors. A strong correlation was noted between invasive lobular carcinoma and hormone receptor expression with 8 out of 9 lobular carcinoma cases (88.9%) classifiable as luminal cancers. Otherwise, there was no association between the molecular class and the histologic type or grade of the tumor. Conclusions: Subtyping by use of this immunohistochemical panel revealed a prevalence pattern that is unique to our population; luminal tumors comprised only 19.9%, and the unclassified group (penta negative) 42.8%, a distribution which is distinctive to our population and in contrast with all Western studies. The presence of a predominant unclassified group also suggests that the currently used molecular analytic spectrum may not completely encompass all molecular classes and there is a need to further refine and develop the existing classification systems.
Expression of 6 Common Antigenic Markers in Invasive Ductal Breast Carcinoma
Applied Immunohistochemistry & Molecular Morphology, 2011
Expression of estrogen (ER) and progesterone receptors, c-erbB-2 oncogene, mutant p53 antioncogene (mp53), e-cadherin adhesion, and apoptotic caspase-8 antigens in tumor relative to matched normal tissue specimens from 102 unselected patients with primary ductal breast carcinoma of various tumor grades was assessed by immunohistochemistry and correlated with patient's biologic and clinical features, such as age, menstrual status, age of menarche, tumor grade and diameter, the presence or absence of metastases, and number of infiltrated lymph nodes. We observed association of e-cadherin adhesion, ER and progesterone antigen marker expression with low histologic grade tumors and limited number of lymph node metastases and of c-erbB-2, mp53, and casp-8 antigen marker expression with high histologic grade tumors and increased number of lymph node metastases. We also observed strong correlation (P<0.05) between 4 of the 6 biomarkers and 4 of the 7 patient/tumor parameters examined. Our findings support the hypothesis of independent expression of these 4 strong biomarkers and reveal that nearly 40% of all breast tumor cases studied express similar proportions of 2 major phenotypic combinations [ER/c-erbB-2/mp53/casp-8: +/+/ À /+ (19.6%) & +/ À / À /+ (17.8%)]. We conclude that, in agreement with earlier reports, our findings support the diagnostic and potential prognostic value of these markers in the clinical assessment of breast cancer.
Cancer, 2010
BACKGROUND: The development of reliable gene expression profiling technology is having an increasing impact on the understanding of breast cancer biology. METHODS: In this study, microarray analysis was performed to establish gene signatures for different breast cancer phenotypes, to determine differentially expressed gene sequences at different stages of the disease, and to identify sequences with biologic significance for tumor progression. Samples were taken from patients before their treatment. After microarray analysis, the expression level of 153 selected genes was studied by real-time quantitative polymerase chain reaction analysis. RESULTS: Several gene sequences were expressed differentially in tumor samples versus control samples and also were associated with different breast cancer phenotypes, estrogen receptor status, tumor histology, and grade of tumor differentiation. In lymph node-negative tumors were identified a set of genes related to tumor differentiation grade. CONCLUSIONS: Several differentially expressed gene sequences were identified at different stages of breast cancer.
Basic and Applied Pathology, 2010
Background and aim: DNA expression profiling studies of breast cancer have identified subtypes including luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) overexpression, and basal-like type. Among them, the basallike type was associated with poor outcome. The purpose of this study was to classify breast carcinoma by immunohistochemistry and evaluate its characteristic histopathologic features. Methods: One hundred and four cases of resected infiltrating ductal carcinoma were immunostained for estrogen receptor, HER2, cytokeratin 5/6 and p63 to classification, and basal-like subtype were evaluated for its histopathologic characteristics. Results: The prevalence of subtypes was luminal A 48.1%, luminal B 24.0%, HER2 overexpression 11.5%, normal breast-like 4.8%, and basal-like 11.5%. There was significant correlation between the basal-like type and histologic grade. And it was significantly associated with several morphological features including expanding growth pattern, presence of tumor necrosis and peritumoral lymphocytic infiltration. Conclusions: The results of this study showed that the basal-like type occupied 11.5% of infiltrating ductal carcinoma and was associated with expanding growth pattern, presence of tumor necrosis and peritumoral lymphocytic infiltration.
International Journal of Breast Cancer, 2011
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.
Molecular phenotypes of matched in situ and invasive components of breast carcinomas
Human Pathology, 2011
The current system of pathologic classification of human breast cancers does not take into account the biologic determinants of prognosis, nor is there a consensus regarding the progression from in situ to invasive carcinoma. The present study compared the molecular phenotypes of in situ and invasive components of breast cancer in the same sample. We built a series of 189 in situ and invasive carcinomas using tissue microarrays and classified them according to their immunoprofiles regarding estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, epidermal growth factor receptor, cytokeratin 5, P-cadherin, and the antigen Ki-67 into luminal A and B, human epidermal growth factor receptor 2 overexpressing, and basal-like carcinomas. We also correlated the subgroups of carcinomas with some of the classical prognostic factors such as histologic grade, tumor size, and lymph node metastasis, as well as with the age of the patient at diagnosis. The overall concordance on the molecular phenotypes between in situ and invasive components was 94%. For the in situ component, 63% of the cases were luminal A; 15%, luminal B; 12%, human epidermal growth factor receptor 2 overexpressing; and 7%, basal-like. Regarding the invasive component, 61% of the cases were luminal A; 16%, luminal B; 12%, human epidermal growth factor receptor 2 overexpressing; and 8%, basal-like. The present study allowed the identification of different immunoprofiles of in situ and invasive breast carcinomas using a specific panel of biomarkers and showed that in most cases, there is a concordance between in situ and invasive component profiles, supporting the theory of parallel disease in breast tumorigenesis.
Clinical Cancer Research, 2013
Purpose: Previous studies of breast tissue gene expression have shown that the extratumoral microenvironment has substantial variability across individuals, some of which can be attributed to epidemiologic factors. To evaluate how mammographic density and breast tissue composition relate to extratumoral microenvironment gene expression, we used data on 121 patients with breast cancer from the populationbased Polish Women's Breast Cancer Study.