Histological Types Of Breast Cancer Research Articles

The butterfly effect in cancer: A single base mutation can remodel the cell

We have compared the proteome, transcriptome, and metabolome of two cell lines: the human breast epithelial line MCF-10A and its mutant descendant MCF-10A-H1047R. These cell lines are derived from the same parental stock and differ by a single amino acid substitution (H1047R) caused by a single nucleotide change in one allele of the PIK3CA gene, which encodes the catalytic subunit p110α of PI3K (phosphatidylinositol 3-kinase). They are considered isogenic. The H1047R mutation of PIK3CA is one of the most frequently encountered somatic cancer-specific mutations. In MCF-10A, this mutation induces an extensive cellular reorganization that far exceeds the known signaling activities of PI3K. The changes are highly diverse, with examples in structural protein levels, the DNA repair machinery, and sterol synthesis. Gene set enrichment analysis reveals a highly significant concordance of the genes differentially expressed in MCF-10A-H1047R cells and the established protein and RNA signatures of basal breast cancer. No such concordance was found with the specific gene signatures of other histological types of breast cancer. Our data document the power of a single base mutation, inducing an extensive remodeling of the cell toward the phenotype of a specific cancer.

Primary breast cancer in the elderly: a systematic literature review on histological type and clinical outcome.

The objective was to determine whether histological types of breast cancer in elderly women influence clinical outcome. Four major databases were searched. All relevant articles, from January 1990 to December 2013, were screened. After applying inclusion and exclusion criteria, 11 studies were included. Invasive ductal carcinoma was the commonest (68.5-87.1%) histological type, followed by lobular carcinoma (6.9-17.7%). Four studies reported on survival. However, none specifically looked at survival according to different histological types. There are very little data on the influence of histological type on clinical outcome in primary breast cancer in elderly patients. Further studies may elucidate any potential influence and its relationship with tumor biology.

Role of serum carcinoembryonic antigen (CEA) as a tumor marker in breast cancer

Background: There is a need for biological prognostic indicators in breast cancer that would, alone or in combination with others, be sufficient to predict disease recurrence and, hence, be the basis for supplemental treatment after local therapy. Aims: To investigate the association between tumor marker serum carcinoembryonic antigen (CEA) and clinicopathological parameters in patients with breast cancer. Methods: A total of 134 patients with breast cancer treated in a single general surgery unit between January 2012 and November 2013 were included in the study, with age ranging between 28 and 73 years. Serum CEA values were compared before and after the treatment of breast cancer, between different histological types of breast cancer patients, between axillary lymphnode-positive and axillary lymphnode-negative patients, and between premenopausal and postmenopausal breast cancer patients. Data were analyzed using the statistical software SPSS version 19. Results: There was significant change in the values of serum CEA before (10.71 ± 2.79 ng/ml) and after the surgery for breast cancer (9.73 ± 3.00 ng/ml) (P < 0.006). There was further decline in the serum CEA level after a course of chemo-radiotherapy (7.30 ± 2.79 ng/ml) (P < 0.001). There was no significant difference between the different histological types of breast cancer (P value 0.55). The difference was significant in patients who were axillary lymphnode positive and negative (P < 0.001). There was no significant difference in premenopausal and postmenopausal breast cancer patients (P value 0.86). Conclusions: Serum CEA is a tumor marker of breast carcinoma. Its level decreased after treatment. This decrease is found more after chemo/radiotherapy following surgery. Serum CEA values are found to be elevated in patients with axillary lymphnode metastasis. There is no significant relation with the histologic type of breast cancer and menopausal status of the patient.

Abstract P4-04-08: Genomic and transcriptomic characterization of papillary carcinomas of the breast

Abstract Introduction: Papillary carcinomas (PCs) are a rare (&amp;lt;1%) special histological type of breast cancer that often affects postmenopausal women, and has an overall favorable outcome. Based on their histological characteristics, these tumors are classified into three different subtypes, namely encapsulated papillary carcinomas (EPC), solid papillary carcinomas (SPC) and invasive papillary carcinomas (IPC). In this study, we sought i) to investigate whether PCs constitute a molecular entity distinct from grade- and ER-matched invasive ductal carcinomas of no special type (IDC-NST) at the transcriptomic level, ii) to investigate whether EPC, SPC and IPC display distinct transcriptomic profiles, iii) to characterize the repertoire of copy number alterations in the different subtypes of PC, and iv) to identify recurrent fusion genes that may be potential drivers of this disease. Material and methods: DNA and RNA were extracted from microdissected PCs (4 SPCs, 5 IPCs and 7 EPCs) and grade- and ER-matched IDC-NSTs (RNA only). 16 PCs and 16 grade- and ER-matched IDC-NSTs were subjected to gene expression profiling using the Illumina Human HT-12 v4 platform. Genes differentially expressed between the PC subtypes were identified using SAM, and functional annotation of these genes was performed using DAVID. Intrinsic molecular subtypes were determined using the PAM50 single sample predictor. Copy number profiling was performed using Affymetrix Human SNP 6.0 arrays with DNA extracted from 16 PCs. In addition, 8 PCs (3 IPCs, 3 EPCs, 2 SPCs) were subjected to paired-end massively parallel RNA sequencing (Illumina GAIIx). Putative expressed fusion transcripts were identified using validated algorithms (i.e. deFuse and Chimerascan), and confirmed by reverse transcription PCR. Results: PCs were preferentially of histological grade I/II (82%) and ER-positive (100%). Unsupervised analysis revealed that PC subtypes show a high degree of similarity at the transcriptomic level, and form clusters distinct from grade- and ER-matched IDC-NSTs. Compared with IDC-NSTs, PCs displayed reduced expression of genes related to cell motility, adhesion and extracellular matrix. PAM50 subtyping classified 87.5%, 50% and 100% of EPCs, SPCs and IPCs as of luminal subtypes, respectively. 12.5% of EPCs were classified as of basal-like subtype, and 50% of SPCs as of HER2-enriched subtype. At the genomic level, PC subtypes displayed similar patterns of gene copy number aberrations. Five in-frame fusion genes, USF1-CCDC38, MDC1-SFTA2, DLD-LMBR1, PDCL-DENND1A and SUGT1-NOL6, were identified and validated in PCs, however none of these were recurrent in the cases included in this study. Conclusion: Our results demonstrate that the majority of PCs are of luminal subtype, and support the contention that at the transcriptomic level, PCs are distinct from grade- and ER-matched IDC-NSTs. Our findings also demonstrate that unlike some other histological special types of breast cancer, PCs are not underpinned by a highly recurrent expressed fusion gene. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-04-08.

Abstract ES03-1: Clinical 101: The pathology of breast cancer

Abstract Numerous histological types of breast cancer are recognized based on their discrete architectural patterns and associated different risk factors, clinical presentations, pathological features, patterns of spread, response to therapy and outcomes. Traditional prognostic factors include tumor size, lymph node status, tumor grade, and immunohistochemical profile of Estrogen and Progesterone Receptor (ER and PR) and Her2/neu gene amplification status. Histological tumor grade assesses degree of differentiation (tubule formation and nuclear pleomorphism) and proliferative activity (mitotic index). The three histological grades mirror aggressiveness and correlate with survival. Expression profiling reveals only two genomic grades, low and high. The ER positive, HER2 positive and triple negative tumors have correlative molecular subtypes on transcriptome analysis; two ER positive groups, luminal A and B where B tumors have a high proliferation compared with A, a HER2 enriched group, and basal-like group corresponding to triple negative tumors. A molecular apocrine group is characterized by ER negative, Androgen Receptor positive status with paradoxical expression of ER related genes and often HER2. A subset of molecular apocrine carcinomas have a morphological correlate. The traditional prognostic factors used to determine therapy neither capture the complexity of breast cancer nor provide tailored enough treatment options for individual patients. Gene expression profiles which predict disease recurrence pick out the proliferation related genes and a number of different prognostic signatures despite them having &amp;lt; 25% of shared genes between the signatures (e.g. OncotypeDX, PAM50, Mammaprint) identify the Luminal A low risk subgroup, which does not benefit from chemotherapy. These prognostic signatures have no value in ER negative disease where there is a high rate of resistance to chemotherapy regimens. Predictors of sensitivity or resistance to specific regimens of chemotherapy in all tumors and predictors of resistance to hormone therapy in ER positive tumors are needed. The low and high grade genomic signatures reflect two distinct models of tumor progression. The low grade neoplasia pathway is characterized by simple diploid karyotypes, and luminal A type invasive carcinomas in this group share genetic and transcriptomic features with precursor lesions, ADH, FEA. Special subtype tumors in this pathway include tubular, lobular, cribriform, mucinous carcinomas and some neuroendocrine carcinomas. The high grade pathway encompasses high grade DCIS, and high grade invasive ductal carcinoma and is characterized by aneuploidy and complex karyotypes. Although tumors can be lumped broadly into low and high grade, there is enormous diversity between tumors even within the molecular subgroups. For example the basal-like/triple negative group includes tumors with distinct morphology, clinical presentation, prognosis and molecular profiles which requires tailoring of therapies. Two rare low grade clinically indolent basal-like tumors include Secretory carcinomas which harbor a characteristic recurrent balanced chromosomal translocation which leads to a fusion transcript ETV6-NTRK3 and Adenoid cystic carcinomas which have a MYB-NFIB fusion gene. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES03-1.

EZH2 expression in invasive lobular carcinoma of the breast

BackgroundInvasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, but the prognosis of ILC is still controversial. Enhancer of Zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2 (PRC2), is frequently overexpressed in various cancers. This study evaluated the relationship between clinicopathologic characteristics and EZH2 expression.MethodsWe retrospectively reviewed the medical records of 54 patients with ILC and selected 49 cases of ILC. Immunohistochemistry for EZH2 was undertaken.ResultsWe defined ILC as discohesive cells with a linear or nonlinear growth pattern. No statistically significant difference was found for most variables, including multifocality, menstrual status, body mass index, tumor stage (pT), lymph node stage (pN), estrogen receptor, and progesterone receptor. In contrast, nuclear grade was statistically significant and EZH2 expression was associated with high nuclear grade. In total, 80% of nuclear grade 3 cases had an EZH2 score of 4, and 86% of nuclear grade 1 cases had EZH2 scores of 1 and 2. Our cases had a score of 3 for tubule formation and a score of 1 for mitosis, and so the histologic grading consisted of grades 1 (7 cases) and 2 (42 cases) depending on the nuclear grade.ConclusionAlthough EZH2 could not predict survival in our study, EZH2 expression was associated with a high nuclear grade. Most ILCs have histologic grade 2 with nuclear grade 2 or 3. Therefore, our opinion is that if ILC is diagnosed by separating the classic type and variants and considering both EZH2 expression and nuclear grade, EZH2 overexpression could help and the Nottingham grading system would be more accurate prognostic factor.

Invasive micropapillary breast cancer: Single-institution experience in the modern era.

150 Background: Invasive micropapillary breast cancer (IMPC) is a rare special histologic type of breast cancer with a propensity for nodal metastases. Molecularly, IMPCs have been classified as luminal B; however, clinical outcome data in the era of targeted therapy are limited. Here we report our institutional experience with IMPC. Methods: We retrospectively reviewed our prospective database from 1995-2009 to identify patients who had surgery for IMPC. Clinical characteristics and outcomes were abstracted from the medical record. Overall survival (OS) was estimated using Kaplan-Meier methods. Factors associated with OS and trends over time were assessed using the log-rank test and Cox regression. Results: We identified 258 patients with IMPC. Median patient age 56yrs (range 26-91), 157(61%) postmenopausal, 147(57%) presented with a palpable mass. The majority of IMPCs were grade 3 (83%), estrogen receptor (ER)-positive (86%) and HER2-neg (81%) with LVI (60%) and nodal metastasis (62%). 194 (75%) patients received chemotherapy (CTX), 204 (81%) hormonal therapy and 37/48 (77%) HER2-pos patients received trastuzumab. At a median follow-up of 55 months (range 1-173mos), 5yr OS is 89.5% with a trend towards improved survival in later yrs; 5 year OS 1995-2005 vs 2006-2009, 85% vs 91%, respectively (p=0.06) Clinical factors associated with OS are shown (Table). Among ER-pos/HER2-neg patients, progesterone receptor (PR) status was strongly associated with 5yr OS. Conclusions: In this large cohort of patients with IMPC treated at a single center, OS was associated with tumor size, PR status, use of CTX and trastuzumab but not with ER or hormonal therapy. These clinical data support the molecular classification of IMPC as luminal B cancers which have a more aggressive clinical behavior than other ER+ cancers. The trend towards improved survival in later years likely reflects the benefits of targeted therapy. [Table: see text]

Out-of-sample extension of diffusion maps in a computer aided diagnosis system. Application to breast cancer virtual slide images

While the pathologist population tends to dramatically drop, the number of pathological cases to be examined increases sharply, mainly due to early screening campaigns; developing automated systems would thus be useful to help pathologists in their daily work. As Virtual Microscopy (VM) is more and more introduced in pathology departments [1] where it holds immense potential despite the large amounts of data to be managed, its combination with image processing techniques can allow to find objective criteria for differential diagnosis or to quantify prognostic markers. Thus, many works try to develop computer-aided diagnosis systems (CADS) based on image retrieval and classification [2,3]. The first step consists in building a knowledge database involving many features extracted from a set of well-known images; it is an 'off-line' procedure conducted once. These features are represented by vectors of non-linear data acting as a signature for the original images. In a second step, signatures are obtained from new unknown images to analyze and compared with the database; it is an 'on-line' procedure. Because of tumor heterogeneity, it is essential to build knowledge databases containing representative features of the multiple morphological types of lesions before considering to implement a CADS. But, as it is almost impossible for a pathologist to manually segment large virtual slide images (VSI), the usual practice consists in manually selecting some 'representative areas'. A bias is then introduced in the process as this choice is obviously subjective. It is then mandatory to find wiser solutions leading to an unbiased collection of these 'representative areas' (and later called 'patches'). In a previous work [4], we have proposed an original strategy: starting from a collection of breast cancer VSI, then taking advantage of stereological sampling methods and diffusion maps, a knowledge database is obtained from a reduced number of patches that are representative of given histological types. The sampling tools offered by stereology are well-suited in this context [5]. Systematic sampling starting from a random point with a fixed periodic interval is able to reduce the area to be analyzed, while preserving the collection of distinctive regions encountered in a tumor. However, even if the working area becomes smaller, the number of selected patches can be very large and may include many redundant elements. A data reduction has then to be conducted. Among the available methods, the diffusion maps technique [6,7] has been retained since it provides a very attractive framework for processing and visualizing huge non-linear bulk data. Diffusion maps belongs to unsupervised learning algorithms dealing with a spectral analysis of non-linear data, providing a clustering only for given training points with no straightforward extension for out-of-sample cases. The work presented here focuses on a way to get around this problem and explains how unknown VSI can be classified by considering the diffusion maps as a learning eigenfunction of a data-dependent kernel. It makes use of the Nystrom formula to estimate diffusion coordinates of new data [8]. An application on histological types of breast cancer is presented with VSI of Invasive Ductal Carcinoma and Mastosis.

Secretory carcinoma of the breast and its histopathological mimics: value of markers for differential diagnosis

Secretory carcinoma (SC) is a rare histological type of breast cancer, and ETV6-NTRK3 gene fusion is highly specific to it. The differential diagnoses of SC include acinic cell carcinoma (ACCA) and cystic hypersecretory carcinoma (CHC), as well as invasive ductal carcinoma (IDC). For patients with these rare but distinctive histological subtypes, SC and its histopathological mimics should be differentiated from each other. However, differential markers have not yet been assessed systematically, and we aimed to identify and evaluate novel and existing markers. We reviewed 19 cases diagnosed initially as SC using integrated diagnostic techniques, including morphology, immunohistochemistry and molecular pathology, and validated promising markers in 445 breast cancers. We reclassified 19 formerly diagnosed 'SCs' into nine SCs, three ACCAs, three CHCs, three IDCs and one microglandular adenosis. We confirmed that ETV6-NTRK3 gene rearrangement and amylase positivity are good diagnostic markers for SC and ACCA, respectively. Vacuolar staining for adipophilin, positivity for α-lactalbumin and negativity for ETV6 rearrangement are diagnostic markers for CHC. In this study, we propose a panel of four markers (ETV6 rearrangement, amylase, α-lactalbumin and adipophilin) for distinguishing SC, ACCA, CHC and IDC. This simple but robust panel will serve pathologists well as a practical guide for reaching an appropriate diagnosis.

Risk Factors for Specific Histopathological Types of Postmenopausal Breast Cancer in the NIH-AARP Diet and Health Study

Risk factor associations for rare breast cancer variants are often imprecise, obscuring differences between tumor types. To clarify differences, we examined risk factors for 5 histological types of breast cancer in the National Institutes of Health-AARP Diet and Health Study. Risk factor information was self-reported. We followed 192,076 postmenopausal women aged 50-71 years from 1995-1996 through 2006. During that time period, 5,334 ductal, 836 lobular, 639 mixed ductal-lobular, 216 mucinous, and 132 tubular breast cancers were diagnosed. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Heterogeneity was evaluated using case-only logistic regression. The strongest differences were for menopausal hormone therapy (Pheterogeneity < 0.01) and age at first birth (Pheterogeneity < 0.01). Risk of tubular cancer in relation to current menopausal hormone therapy (for current use vs. never use, hazard ratio (HR) = 4.39, 95% confidence interval (CI): 2.77, 6.96) was several times stronger than risk of other histological types (range of HRs, 1.39-1.75). Older age at first birth was unassociated with risk of mucinous (for ≥30 years vs. 20-24 years, HR = 0.62, 95% CI: 0.27, 1.42) or tubular (HR = 1.08, 95% CI: 0.51, 2.29) tumors, in contrast to clear positive associations with lobular (HR = 1.82, 95% CI: 1.39, 2.37) and mixed ductal-lobular (HR = 1.87, 95% CI: 1.39, 2.51) tumors. Differing associations for hormonal factors and mucinous and tubular cancers suggest etiologies distinct from those of common breast cancers.

MicroRNA and histopathological characterization of pure mucinous breast carcinoma.

ObjectivePure mucinous breast carcinoma (PMBC) is an uncommon histological type of breast cancer characterized by a large amount of mucin production. MicroRNA (miRNA) is a large class of small noncoding RNA of about 22 nt involved in the regulation of various biological processes. This study aims to identify the miRNA expression profile in PMBC.MethodsMiRNA expression profiles in 11 PMBCs were analyzed by miRNA-microarray and real-time polymerase chain reaction (PCR). Thirty-one PMBCs and 27 invasive ductal carcinoma of no special types (IDC-NSTs) were assessed by immunohistochemistry using antibodies against ER, PR-progesterone receptor, HER2, Ki-67, Bcl-2, p53, PCNA, and CK5 and 6.ResultsWe analyzed the miRNA expression in 11 PMBCs and corresponding normal tissues using miRNA-microarray and real-time PCR, and found that miR-143 and miR-224-5p were significantly downregulated in mucinous carcinoma tissue. Compared with IDC-NSTs, PMBC showed a significantly higher ER positive rate, lower HER-2 positive rate, and lower cell proliferation rates.ConclusionsTo our knowledge, this is the first study to demonstrate the miRNA expression profile of PMBC, and our findings may lead to further understanding of this type of breast cancer.

Breast cancer leptomeningeal metastasis: propensity of breast cancer subtypes for leptomeninges and the analysis of factors influencing survival

The aim of the study was to define biological subtypes of breast cancer that have the propensity to metastasize to the leptomeninges and to assess factors influencing survival from detection of leptomeningeal metastatis (LM). One hundred and eighteen consecutive breast cancer patients with LM were treated in one institution, between the years 1999 and 2009; 40.5 % of patients had triple-negative subtype, 37.5 % had luminal A subtype and 22 % had HER2-positive subtypes (luminal B and HER2). Of patients with LM, 35 % had lobular cancer. Median survival from the detection of LM was 18 weeks, and 1-year survival was 16 %. Cox multivariate analysis revealed that performance status and systemic treatment statistically significantly influenced survival of patients with LM. Triple-negative biological subtype and lobular histological type of breast cancer had the propensity to metastasize to the leptomeninges. Performance status and systemic treatment ordered after detection of LM statistically significantly influenced survival.

Histological Type and Tumour Grade in Nigerian Breast Cancer: Relationship to Menarche, Family History of Breast Cancer, Parity, Age at First Birth, And Age at Menopause

s: Background: The high burden of disease due to breast cancer has continued to have its toll on global health, without exception to Nigeria. The menace of late presentation, with resultant poor survival rates, may be better contained, with improved understanding of the disease characterization in our local settings. Objective: to determine the distribution of tumor grades and histologic types of breast cancer, in Calabar Methodology: retrospective study of eighty-one (81) cases, with use of hospital records Results: Most of the patients were young, with a mean age of 45.06 years, and 30-39 years being the commonest age group (38.3%). They were mostly non-menopausal (72.6%) urban residents (72.2%). As in similar local and international studies, invasive ductal carcinoma was the most prevalent histologic type (85.2%). Grade 3 tumors were most prevalent (66.7%), while grade 1 tumors were least commonly seen (9.9%), with no significant difference in tumor grades across the various socio-demographic and notable risk factors. Recommendations And Conclusion: high prevalence of late stage presentation in our young women is a cause of public health concern, with urgent need for early detection, especially through wide coverage of breast cancer education and screening programs. In-depth interviews, with further case-control studies using larger samples, is required for better understanding of the determinants of tumor grades and histologic types, towards disease prevention and effective health service delivery.

Expressional Correlation of Human Epidermal Growth Factor Receptor 2, Estrogen/Progesterone Receptor and Protein 53 in Breast Cancer

This study aimed to show the localization of estrogen / progesterone receptors, human epidermal growth factor receptor 2 (Her-2) and protein 53 (p53) by immunohistochemistry in a series of consecutive breast cancer patients. The study covered invasive breast cancers from 299 patients presenting at the Oncogenetic Clinic and Pathology Centers of Ahwaz Jondishapour University of Medical Sciences Hospital in Iran during the time period from 2009 to 2011. The Scarff-Bloom Richardson scoring method was used. Of the 299, 27% (80/299) were <40, 33% (100/299) were 41-50, and the remaining 40% (119/299) were>50 years old. The highest incidence of breast cancer in this study population was in the group of more than 50 year age, and the most common histological type of breast cancer was the invasive ductal carcinoma, which accounted for 68% (203/299) of the cases. Out of possible total of 207, 6% (13/207), 41% (85/207), and 53% (109/207) were scored as grade ?, ??, ???, respectively. Our findings demonstrated a lack of association between labeling for the markers studied and tumor size and age of the patients. We confirmed an association between ER labeling and nuclear grade of breast cancer. The conflicting results obtained compared with the literature be because of differences in the immunohistochemical techniques applied in the various studies and to the scoring systems used.

Clinico-pathological study of breast carcinoma: A prospective two-year study in a tertiary care hospital

Background: Breast cancer is the most frequent cancer in female, both in developed and developing regions, and ranks second overall next only to lung cancers. International variation in both incidence and mortality is one of the most striking features of breast cancer. Aims: To assess the clinical profile of the patients of breast carcinoma as well as relevant macroscopic and microscopic features of the mastectomy specimens. Materials and Methods: The present prospective study was carried out on clinically suspected and pre-operative FNAC-confirmed 120 cases of breast carcinoma who were admitted in the department of surgery for mastectomy during the study period of two years. In addition to relevant clinical features, macroscopic and microscopic features of mastectomy specimens were noted. Results: Mean age of the study population was 46.53 years. Most of the patients presented with breast lump with or without other features. Mean tumor size in the study population was 5.91 cm with standard deviation ± 2.59. Most of the cases (90.8%; 109 cases out of 120 cases) were diagnosed as IDC, NOS (Infiltrating ductal carcinoma, not otherwise specified). Mostly (62 cases; 51.7%), we got the histological grade 3 tumors. Lympho-vascular invasion was identified in 25.8% cases (31 cases out of 120 cases). Skin and nipple areola was involved in 15.0% cases (18 cases). Conclusion: IDC, NOS is the most common histologic type of breast cancer in our study population. Most commonly affected age group by breast cancer is 35-50 years. In most of the cases, size of the mass was more than 5 cm involving multiple quadrants of breast and with positive lymph nodes. Histologically, grade 3 tumor is most prevalent in this population.

Magnetic resonance in the detection of breast cancers of different histological types.

Breast cancer incidence is increasing worldwide. Early detection is critical for long-term patient survival, as is monitoring responses to chemotherapy for management of the disease. Magnetic resonance imaging and spectroscopy (MRI/MRS) has gained in importance in the last decade for the diagnosis and monitoring of breast cancer therapy. The sensitivity of MRI/MRS for anatomical delineation is very high and the consensus is that MRI is more sensitive in detection than x-ray mammography. Advantages of MRS include delivery of biochemical information about tumor metabolism, which can potentially assist in the staging of cancers and monitoring responses to treatment. The roles of MRS and MRI in screening and monitoring responses to treatment of breast cancer are reviewed here. We rationalize how it is that different histological types of breast cancer are differentially detected and characterized by MR methods.

Immunohistochemical analysis of medullary breast carcinoma autoantigens in different histological types of breast carcinomas

BackgroundOn the past decade a plethora of investigations were directed on identification of molecules involved in breast tumorogenesis, which could represent a powerful tool for monitoring, diagnostics and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile in different histological types of breast cancer.MethodsSemi-quantitative immunohistochemical analysis of 20 tissue samples including medullary breast carcinoma, invasive ductal carcinoma, invasive lobular carcinoma and non-cancerous tissues obtained from patients with fibrocystic disease (each of five) was performed using specifically generated polyclonal antibodies. Differences in expression patterns were evaluated considering percent of positively stained cells, insensitivity of staining and subcellular localization in cells of all tissue samples.ResultsAll 6 antigens predominantly expressed in the most cells of all histological types of breast tumors and non-cancerous tissues with slight differences in intensity of staining and subcellular localization. The most significant differences in expression pattern were revealed for RAD50 and LGALS3BP in different histological types of breast cancer and for PABPC4 and FAM50A antigens in immune cells infiltrating breast tumors.ConclusionsThis pilot study made possible to select 4 antigens LGALS3BP, RAD50, PABPC4, and FAM50A as promising candidates for more comprehensive research as potential molecular markers for breast cancer diagnostics and therapy.Virtual slidesThe virtual slides’ for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1860649350796892

Breast Cancer: Distribution of Histology Type at Santo Antonio Hospital in Salvador, Bahia, Brazil

INTRODUCTION: Breast cancers are a heterogeneous group of tumors that show various clinical presentations biological behaviors and prognostic. Each histological type also have different responses to loco-regional and systemic treatments. Currently, despite advances in immunohistochemistry of tumors, the histological result is still important to define and plan the best treatment management. Nevertheless the incidence of the histological types varies in different units due to non uniform criteria used by pathologists and also to a certain degree of subjectivity. AIM: Know the frequency of malignant breast tumors at the mastology unit in Hospital Santo Antonio, comparing the results to overall literature. MATERIALS AND METHODS: All tumors from patients operated of malignant tumors of the breast were submitted to histological analyses at Hospital Santo Antonio, Salvador Bahia Brazil from February 2010 to may 2012. RESULTS: 191 patients were evaluated during the period. 154 patients (80, 63%) invasive ductal carcinoma (NOE) ; 15 patients (7, 85%) ductal carcinoma “in situ” ; 4 (2, 09%) papillary invasive carcinoma; 1 (0, 52%) non invasive papillary carcinoma; 2 (1, 05%) invasive lobular carcinoma; 5 (2, 62%) mucinous carcinoma; 1 (0, 52%) micro papillary carcinoma; 1 (0, 52%) squamous cell carcinoma; 2 (1, 05%) cribiform carcinoma; 2 (1, 05%) metaplasic carcinoma; 1 (0, 52%) medullary carcinoma; 1 (0, 52%) pseudosarcomatous carcinoma; and 2 (1, 05%) Paget’s disease. DISCUSSION: The rates of invasive ductal carcinoma (NOE), invasive papillary carcinoma, medullary and mucinous invasive carcinomas are according to literature. The rates of lobular carcinoma, and cribifrom carcinoma are well below expected possibly due to the low number of pacients in the study, another hypothesis would be the lack of interpretation uniformity. Despite the Brazilian breast cancer screening program, the rates of ductal carcinoma “in situ” is still very low compared to the increasing incidence in other countries. Pointing out that this country must improve access of patients to mammography. CONCLUSSION: The frequency of histological types of breast cancer at the mastology unit in Hospital Santo Antonio Salvador Bahia Brazil is according to literature except for lobular and cribiform carcinoma. The access of low income patients to mammography is still low, therefore the low incidence of non invasive forms. Showing that screening should be increased as should education about the subject.

Outcome of rare types of breast cancer in Hispanic woman.

96 Background: Rarer histological types of breast cancer represent less than 5% of all cases. The identification might be of value in assessing prognosis and predicting response to therapy in a Hispanic population. Methods: A total of 1,400 consecutive woman diagnosed with any type of breast cancer between 1991 and 2010 were identified. Histological types were classified according to World Health Organization criteria and the Armed Forces. Ductal, lobular and mixed ductal/lobular carcinomas and women with missing data were excluded, leaving a total of 60 patients. Tumor grade, vascular invasion, hormonal receptor status, ki-67 labeling index, HER2 overexpression, tumor size and nodal status were recorded and analyzed by histologic type. Survival curves were calculated by histology. Results: A total of 60 patients were classified according histology in order of frequency as mucinous (36.7%), medullary (10%), papillary (8.3%), metaplastic (8.3%), tubulo-lobular (6.7%), tubular (5.0%), metaplastic with epidermoid differentiation (3.3%), signet cell adenocarcinoma (3.3%), apocrine (3.3%), neuroendocrine (3.3%), acinary (1.7%), histiocytoid (1.7%), leiomyosarcome (1.7%), phyllodes (1.7%), high grade sarcoma (1.7%), and mucinous papillary (1.7%). Women with leiomysarcome type had the youngest mean age at diagnosis (27y) followed by mucinous (32y), and high grade sarcoma was the oldest mean age (76yrs). Most of histologists (82%) presented as stage I and II at diagnosis. Only mucinous, medullary and metaplastic presented with advanced disease (4%). With respect to ER/PR status, 36% of mucinous cases and 60% of papillary cases were ER+/PR+, while 50% of medullary cases and 60% of metaplastic cases were ER−/PR−. Only 13% had overexpression of HER2. Compared with OS reported for ductal and lobular carcinoma, median survival was significantly longer 54 months (40.4–67.5) and DFS median 66.1 months (48-82 months). Conclusions: Rare breast carcinomas are a heterogeneous group with more favorable prognosis compared to ductal carcinoma. Though many of these histologic subtypes are quite rare, an accurate and reliable histopathology assessment is crucial in order to determinate treatment, principally to the need for systemic treatment.

Deep sequencing reveals small RNA characterization of invasive micropapillary carcinomas of the breast

Invasive micropapillary carcinoma (IMPC) is an uncommon histological type of breast cancer. IMPC has a special growth pattern and a more aggressive behavior than invasive ductal carcinomas of no special types (IDC-NSTs). microRNAs are a large class of non-coding RNAs involved in the regulation of various biological processes. Here, we analyzed the small RNA transcriptomes of five formalin-fixed paraffin-embedded (FFPE) pure IMPC samples and five FFPE IDC-NSTs samples by means of next-generation sequencing, generating a total of >170,000,000 clean reads. In an unsupervised cluster analysis, differently expressed miRNAs generated a tree with clear distinction between IMPC and IDC-NSTs classes. Paired fresh-frozen and FFPE specimens showed very similar miRNA expression profiles. By means of RT-qPCR, we further investigated miRNA expression in more IMPC (n=22) and IDC-NSTs (n=24) FFPE samples and found let-7b, miR-30c, miR-148a, miR-181a, miR-181a*, and miR-181b were significantly differently expressed between the two groups. We also elucidated several features of miRNA in these breast cancer tissues including 5' variability, miRNA editing, and 3' untemplated addition. Our findings will lead to further understanding of the invasive potency of IMPC and gain an insight into the diversity and complexity of small RNA molecules in breast cancer tissues.