Parameters In Breast Carcinoma Research Articles

Expression of p16 protein in breast cancer.

Breast cancer is themost common cancer and aleading cause ofdeath in women in Saudi Arabia. P16 is atumour suppressor gene that plays acrucial role in regulating cell cycle. Several studies have investigated thesignificance ofp16 expression in various cancer types. However, thesignificance ofp16 in breast cancer remains controversial and insufficiently studied. Thepresent study aims to examine theassociation between p16 expression and clinicopathological factors in breast cancer using immunohistochemistry staining. Thestudy utilised 475 prospectively collected tissue samples from 475 women with breast cancer in Saudi Arabia. Nuclear and cytoplasmic immunohistochemical staining ofp16 was observed in 338 (71%) ofthecases and showed significant direct associations with adverse tumour features, including high tumour grade (p < 0.0001), negative oestrogen receptor/progesterone receptor status (p < 0.001), and lymph node metastasis (p = 0.02). Our study revealed asignificant association between p16 protein expression and theestablished negative prognostic parameters in breast carcinoma including tumour grade, lymph node metastasis, and oestrogen receptor and progesterone receptor status.

Meme Karsinomlarında ER, PR, c-erbB2, Ki67, E-Cadherin Ekspresyonları, Nottingham Histolojik Grade ve Bazı Klinik Parametreler Arasındaki İlişkilerin Değerlendirilmesi

Objective: In this study, it was aimed to evaluate the relationships between Estrogen receptor (ER), Progesterone receptor (PR), c-erbB2 (HER2), Ki67, E-Cadherin expressions, Nottingham histological grade and some clinical parameters in breast carcinomas. Materials and Methods: A total of 74 patients diagnosed with breast carcinoma (CA) in our pathology department between 2018-2019 were included in this study. Immunohistochemical preparations stained with ER, PR, HER2, Ki67 and E-Cadherin were evaluated and analyzed retrospectively. For ER and PR, ≥1% expression was considered as positive staining, and &amp;lt;1% was considered as negative staining. HER2 expression was scored as 0, 1, 2 and 3. Ki67 proliferation index was considered as low (&amp;lt;10%), intermediate (10-20%) and high risk (&amp;gt;20%). The data were analyzed with chi-square test. Results: HER2 score showed a statistically significant change according to ER status (p=0.010). HER2 score also showed a statistically significant change according to PR status (p=0.004). There was a significant correlation between Ki67 and histological stage (p&amp;lt;0.001). Conclusions: Detection of high Ki67 index in breast carcinomas is poor prognostic. Detection of ER and PR expression and no expression of HER2 are good prognostic indicators. Preanalytical and analytical processes should be followed meticulously by pathologists.

Association of Serum Fibrinogen and Plasma VEGF Levels with Tumor Characteristics and Treatment Response in Operable Breast Carcinoma

A search for factors predicting the behavior of the tumor, its invasiveness, metastasis, response to treatment, and prognosis is the primary focus of breast cancer research. The objective of the present study was to study the association of fibrinogen and vascular endothelial growth factor (VEGF) with various parameters of breast carcinoma. A case control was conducted in which fibrinogen, and VEGF levels were compared between cases and controls and also with various characteristics of breast carcinoma such as T stage, lymph node positivity, grade, lymphovascular invasion, and receptor status. The effect of surgery of breast cancer on fibrinogen and VEGF levels was also studied. The levels of fibrinogen and VEGF were significantly higher in cases when compared to controls (p < 0.001). Increased fibrinogen level was significantly associated with higher grade of the tumor, lymph node metastasis, and lymphovascular invasion. Increased VEGF level was significantly associated with higher grade and lymphovascular invasion of the tumor. After treatment, there was a statistically significant fall in the levels of the above mediators (p < 0.001). Serum fibrinogen and plasma VEGF levels were significantly higher in patients of breast carcinoma and had significant association with invasiveness of the tumor.

Correlation of proliferative index with various clinicopathologic prognostic parameters in breast carcinoma

Introduction: Breast cancer (BC) is the most common cancer and the second most common cause of death in women. Prognostic factors are essential in BC diagnosis as they allow the identification of high-risk patients, for whom, an adjuvant therapy can improve prognosis. Interest in Ki-67 has recently increased as Ki-67 is a potential marker for predicting the responsiveness to chemotherapy. Materials and Methods: The study was conducted on 75 consecutive cases of primary breast carcinoma undergoing radical or modified radical mastectomy specimen. Histopathological diagnosis was established on routine hematoxylin and eosin stain and various histologic prognostic parameters including histologic type, histologic grade, and lymph node metastases were assessed. All biopsy proven carcinoma breast were included in this study. Results: Among presenting compliant, 47 (62.66%) had lump in right breast and 28 (37.33%) had lump in left breast. Most patients in the study population presented with a lump of duration 3-6 months (54.6%). Out of 75 participants, 41 (62.66%) participants were diagnosed with carcinoma right beast and 28 (37.33%) with carcinoma left breast. On staging the disease among the study population, most of them diagnosed with breast cancer were of stage IIIB (48%) followed by IIA (25.33%).

The relationship oftumour-associated macrophages (CD68, CD163, CD11c) and cancer stem cell (CD44) markers with prognostic parameters in breast carcinomas.

In invasive breast cancer (IBC), tumour-associated macrophages and cancer stem cells in thetumour microenvironment are thought to be associated with poor prognosis, tumour growth, and metastasis. In this study, we evaluated therelationship ofCD68, CD163, CD11c, and CD44 expressions in thetumour microenvironment ofIBC with prognostic parameters by immunohistochemical method. Acorrelation was found between high histological grade, oestrogen receptor/ progesterone receptor negativity, and high Ki-67 index in IBC, and thenumber ofCD68-, CD163-, and CD11c-positive macrophages in thetumour microenvironment. In addition, in thetumour microenvironment, acorrelation was found between IBC-specific subtypes and CD68, luminal Asubtype relative to luminal B and CD163, HER2 score 3 cases, and CD11c-positive macrophage count. It was observed that CD44 expression in thetumour in IBC was not associated with theparameters examined. In addition, ahigh-level linear correlation was found between CD68- and CD163- and CD11c-positive macrophage counts. Tumour-associated macrophages in thetumour microenvironment in IBC may be anovel prognostic factor and an alternative avenue for targeted therapies. The fact that CD44 positivity in thetumour is not associated with prognostic parameters will contribute to theliterature in this direction.

A study on Nottingham prognostic index and its correlation with ER, PR, HER-2/NEU AND KI-67 in breast carcinomas

Aim: Carcinoma of the breast is one of the most common malignancy in women. Considering the tumour size, histological grade and number of lymph nodes involved, Nottingham Prognostic index (NPI) is calculated. This study has been designed to acquire information about various parameters in breast carcinomas and to calculate NPI score in each case and determine the relationship of NPI with various prognostic markers in breast carcinomas. Materials and Methods: The present study was undertaken in the Department of Pathology, Father Muller Medical College, Mangalore for a period of two years. Breast cancers, diagnosed as Invasive carcinoma breast of no special type on lumpectomy and mastectomy was studied and cases were assessed with regard to age, laterality, quadrant involved, size of the tumour, lymph node status, modified SBR grade, hormonal receptor status (ER, PR), HER-2/Neu, Ki-67 and NPI status of the tumour. Statistics: Cross tabulation was done to check for correlation and Kappa statistics was done to check the level of agreement between NPI and modified SBR grade, ER, PR, HER-2/Neu and Ki-67. Results and Conclusion: This study included a total of 100 infiltrating ductal carcinomas of the breast. The mean age of presentation was 52.05 years. On cross tabulation of NPI with pathological parameters only modified SBR grade showed statistically significant association with NPI at 5% level of significance(‘p’ Keywords: Breast neoplasms, Carcinoma, Ductal, NPI.

Relationship between Lymph Node Metastasis and a Low 18F-FDG PET/CT Axillary SUVmax Value in Breast Cancer.

To evaluate breast cancer patients with low F18-fluorodeoxy-glucose positron emission tomography/computed tomography scan (FPET) of axilla standardised maximum uptake value (SUVmax) along with their histopathological findings regarding axillary lymph node metastasis (LNM). A descriptive study. Place and Duration of the Study: Adana City Education and Research Hospital, Turkey, from January 2015 to October 2018. The current study analysed the findings of 113 patients according to age, histopathological axillary LNM, estrogen and progesterone receptor status, tumour size, histological grade, Ki-67, HER2 and preoperative FPET SUVmax findings. Histopathological and immunohistochemical comparisons were made between FPET axilla SUVmax and univariate and multivariate parameters in breast carcinoma in terms of LNM. The authors analysed the receiver operator characteristic curve for the FPET axilla SUVmax and set the cut-off value to 1.84 to predict LNM. However, it was also found that the SUVmax detected metastases in the axilla at values lower than 1.84. In the multivariate analysis, a statistically significant relationship was found between axilla LNM cases that have FPET axilla SUVmax less than 1.84, a Ki-67 index greater than 15% and tumour size greater than 2 cm (p <0.05). Values that were above the axilla SUVmax limit of 1.84 in FPET helped determine LNM. However, further evaluation of patients is needed comparing axilla SUVmax of less than 1.84 in FPET together with the Ki-67 proliferation index and tumour size. Key Words: Breast, Cancer, Lymph nodes, Metastasis, PET, Pathology.

Correlation between the presence of androgenic receptors and molecular and histopathological variables in breast cancer

Introduction: The expression of androgenic receptors (AR) is a new predictive marker of response and prognosis in invasive breast carcinoma (BC). It emerges as a potential therapeutic target. Objective: To evaluate the frequency of AR positivity and its correlation with molecular and histopathological parameters in infiltrative BC. Method: Retrospective cohort study, analyzing 119 cases of invasive non-metastatic BC, seen at a private clinic. Hormonal receptors were screened by immunohistochemical reaction, and AR were considered positive when present in at least 10% of cells, ER and PR from 1%. This finding was correlated with pathological staging, histological grade (HG), vascular-lymphatic invasion (VLI), estrogen (ER) and progesterone receptors (RP), HER2 and Ki 67. Results: Androgen receptors were positive in 80.6% of cases. In the assessment of pathological staging, of the 63 patients with stage I, 81% showed positive androgen receptors, while among the 28 patients with stage II, 75% had positive androgen receptors, and 88% of the 17 patients with stage III presented the positivity of the recipient. Regarding the histological parameters of the tumor, 16 patients had grade 1 tumors, 93.7% of them with positive androgen receptors, while among the 63 with grade 2 tumors 90.4% had androgen receptor positivity, and only 59, 3% of the 27 tumors evaluated as grade 3 had a positive androgen receptor. The vascular-lymphatic invasion was negative in 57 patients, 78.9% of the tumors with positive androgen receptor. Among the 56 tumors with positive vascular-lymphatic invasion, 85.7% had an androgen receptor positivity. In the immunohistochemical evaluation of tumors, among the 95 patients with positive estrogen receptors, 91.5% also had positive androgen receptor, which was positive in only 37.5% of the 24 patients with negative estrogen receptors. Of the 21 patients who had tumors with overexpressed HER, 85.7% also had positive androgen receptors, which were also positive in 86.4% of 96 without overexpression of HER2. In the evaluation of cell proliferation by the Ki67 antigen, among the 50 tumors with Ki67 &lt;20%, 94% had positive androgen receptors, while 83.7% were positive among the 49 tumors with Ki67 between 20 and 50% and only 35% positivity of androgen receptors in 17 tumors with Ki67&gt; 50%. Conclusions: AR positivity is associated with more differentiated hormone-dependent tumors with a lower proliferation rate.

The Association of HER-2 Over-expression in Relation to Hormonal Receptor Status and Common Clinico-pathological Parameters in Breast Carcinoma

Objective: To determine the association of Human Epidermal growth factor Receptor2 (HER-2) with hormonal receptor status and common clinico-pathological parameters of breast carcinoma. Study Design: Cross-sectional, observational study. Place and Duration of Study: Department of Surgery, Sir Salimullah Medical College Mitford Hospital, Dhaka, Bangladesh during the period from January 2009 to December 2009. Methodology: A total of 100 patients of female breast carcinoma with HER-2 status, hormonal receptor profile and clinico-pathological parameters were included in this study. Patient's age, menopausal status, tumour size, lymph node status, Estrogen Receptor (ER) and Progesterone Receptor (PR) status were evaluated and their association was determined with H.ER-2 over expression using the chi-square test for analysis. Results: Of these 100 cases, mean age of diagnosis was 48 years and mean tumour size 4.4 cm. Lymph node metastases were present in 50% cases. HER-2 over-expression was seen in 29% cases, while ER and PR expression was seen in 61 % and 43% respectively. ER and PR showed inverse association (p &lt;0.05) with HER-2 while positive association was seen with tumour size and lymph node metastases (p &lt;0.05). No association was seen with menopausal status. Further, among 61 ER positive cases, 4 cases also HER-2 over expressed. Conclusion: The study had indicated that Her-2 may be a powerful predictor of poor prognosis as its over-expression was strongly directly associated with tumor size and lymph node involvement and inversely associated with hormonal receptor status of breast carcinoma. ER positive cases can also be HER-2 over expressed (4%), so ER status cannot be used to select tumours for evaluation of HER-2 status. As treatment modalities of ER positive and HER-2 over expressed is different, so all the patients should be studied with both receptor and treat accordingly.&#x0D; Journal of Surgical Sciences (2012) Vol. 16 (2) : 59-67

Are Pathological Parameters in Breast Carcinoma Underestimated? Results Correlation in Comparison With Oncotype Dx Testing in Breast Carcinoma Patients in Saudi Arabia

Are Pathological Parameters in Breast Carcinoma Underestimated? Results Correlation in Comparison With Oncotype Dx Testing in Breast Carcinoma Patients in Saudi Arabia

Relationship between primary tumour 18F-FDG uptake and immunohistochemical and clinical prognostic parameters in breast carcinoma

ObjectiveThe objective of this study was to investigate the relationship between level of 18F-fluorodeoxyglucose (18F-FDG) accumulation in primary breast tumour assessed by positron emission tomography/computed tomography (PET/CT) and histopathological and clinical prognostic factors. Material and methodsA retrospective analysis was performed using the medical records of 58 female patients (age range: 31-86 years, mean age: 56) with biopsy of proven breast carcinoma, and who had undergone 18F-FDG PET/CT examination before chemotherapy/surgery. The 18F-FDG uptake of breast tumours was calculated as tumour to background ratio (TBR), which was compared with histopathological and clinical prognostic parameters. ResultsThe histology of the breast tumour in the 58 patients was ductal type in 52 (90%), lobular in 4 (7%), and mucinous in 2 (3%). Tumour size was ≤ 2cm in 31 (53%) patients, and>2cm in 27 (47%). The levels of TBRs were not significantly different between the patients groups with tumours of 2cm or less and greater than 2cm (P=0.131). No significant difference between levels of TBR was observed neither with regards to axillary lymph node involvement (P=0.065) nor in terms of distant metastases (p=0.123). No statistically significant difference was found in levels of TBRs between patients with c-erbB-2 receptor positive and negative ones (P=0.107). Progesterone receptor (PR) expression was observed in 33 patients (57%), and 25 patients (43%) were PR negative. As regards progesterone receptor status, a statistically significant difference was observed in mean TBR levels between patients with and without progesterone receptor expression (P=0.020). Oestrogen receptor expression was positive in 41 (71%) patients, and negative in 17 (29%) patients. The difference in the levels of TBRs between patients with and without oestrogen receptor expression was at the level of significancy (P=0.050). ConclusionsIt is concluded that 18F-FDG uptake correlates with progesterone negativity of the tumour. However, a significant association with clinical prognostic parameters and level of 18F-FDG uptake levels could not be demonstrated.

Immunohistochemical features of multifocal and multicentric lobular breast carcinoma

PurposePatient age, tumor size, axillary lymph node status, expression of estrogen, progesterone and HER2 receptors, as well as the histological grade, are widely accepted prognostic and predictive parameters in breast carcinoma. In invasive lobular carcinoma (ILC), the prognostic factors, such as nodal status and tumor size are believed to be the most valuable ones. The aim of this was set to determine the possible linkage between MFity/MCity of ILC and immunohistochemical predictive (ER, PR, HER2) and prognostic parameters (BRCA1, p53, E-cadherin, Ki-67). Material/methodsOut of 2486 cases diagnosed with BC from south-eastern Serbia, the presence ILC was noted in 334 cases. Immunohistochemical characterization of predictive and prognostic parameters in ILC was done. ResultsThe occurrence of multifocal (MFC) and multicentric carcinoma (MCC) was observed in 18.9% of ILC. Bilateral (BL) BCs were found to be statistically significantly more frequent in younger women, compared to those with MFC, MCC or nonMFC/MCC/BL. No significant correlation was found between MFC/MCC and the presence of axillary lymph node metastases, and expression of immunohistochemical predictive and prognostic parameters. Based on literature data and the findings from the current work, MFity/MCtiy might represent negative morphologic prognostic parameters in ILC. ConclusionsIn 334 cases analyzed, no statistically significant correlations were observed between MF/MC and the expression of immunohistochemical predictive and prognostic parameters.

Association of ICAM-1, VCAM-1, CYCLIN D1 and Cathepsin D with Clinicopathological Parameters in Breast Carcinoma; an Immunohistochemical Study.

Breast carcinoma is the most common malignant tumor detected in women. The hypothesis that increased levels of adhesion molecules and Cathepsin D affect cancerous cells moving away the primary tumor and contributes to migration of the cancerous cell and may cause remote organ metastases is defended. The aim of the present study was to search the association of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), Cyclin D1, cathepsin D immunohistochemically with clinicopathological parameters in the patients diagnosed with invasive ductal breast carcinoma. The pathological slides of 153 patients diagnosed with invasive ductal carcinoma were evaluated retrospectively. Three groups were created. Group 1 consisted of patients with positive lymph node metastasis and extranodal tumor invasion; Group 2 consisted of patients with positive axillary lymph node metastasis and negative extranodal tumor invasion and Group 3 consisted of the patients with negative axillary lymph node metastasis. In all groups, 20 paraffin blocks belonging to the primary tumor in the breast were stained by ICAM-1, VCAM-1, Cyclin D1 and Cathepsin D. Findings were examined by comparing with clinicopathological parameters. The highest number of metastatic axillary lymph nodes and the highest rate of cathepsin D staining were statistically found in the cases with positive axillary lymph node metastasis and extranodal tumor invasion. CerbB2 was negative in the cases with negative ICAM-1 whereas estrogen receptor and progesterone receptor were positive in the cases with positive VCAM-1. The present study reveals significant results for the patients diagnosed with invasive ductal carcinoma through breast biopsy especially before mastectomy in terms of increased number of metastatic axillary lymph nodes and extranodal tumor invasion by immunohistochemical Cathepsin D stain without any additional invasive intervention. Results of the present study may contribute to monitoring and treatment of the patients in the future.

Relationship between primary tumour 18F-FDG uptake and immunohistochemical and clinical prognostic parameters in breast carcinoma.

The objective of this study was to investigate the relationship between level of 18F-fluorodeoxyglucose (18F-FDG) accumulation in primary breast tumour assessed by positron emission tomography/computed tomography (PET/CT) and histopathological and clinical prognostic factors. A retrospective analysis was performed using the medical records of 58 female patients (age range: 31-86 years, mean age: 56) with biopsy of proven breast carcinoma, and who had undergone 18F-FDG PET/CT examination before chemotherapy/surgery. The 18F-FDG uptake of breast tumours was calculated as tumour to background ratio (TBR), which was compared with histopathological and clinical prognostic parameters. The histology of the breast tumour in the 58 patients was ductal type in 52 (90%), lobular in 4 (7%), and mucinous in 2 (3%). Tumour size was ≤ 2cm in 31 (53%) patients, and>2cm in 27 (47%). The levels of TBRs were not significantly different between the patients groups with tumours of 2cm or less and greater than 2cm (P=0.131). No significant difference between levels of TBR was observed neither with regards to axillary lymph node involvement (P=0.065) nor in terms of distant metastases (p=0.123). No statistically significant difference was found in levels of TBRs between patients with c-erbB-2 receptor positive and negative ones (P=0.107). Progesterone receptor (PR) expression was observed in 33 patients (57%), and 25 patients (43%) were PR negative. As regards progesterone receptor status, a statistically significant difference was observed in mean TBR levels between patients with and without progesterone receptor expression (P=0.020). Oestrogen receptor expression was positive in 41 (71%) patients, and negative in 17 (29%) patients. The difference in the levels of TBRs between patients with and without oestrogen receptor expression was at the level of significancy (P=0.050). It is concluded that 18F-FDG uptake correlates with progesterone negativity of the tumour. However, a significant association with clinical prognostic parameters and level of 18F-FDG uptake levels could not be demonstrated.

English

BACKGROUND : Carcinoma of the breast has clinical heterogeneity with high morbidity and mortality. Determination of prognostic factors is important in improving the overall survival breast cancer patients. Her2/neu is one of the powerful predictors of poor prognosis. Thus a study of Her2/neu expression estimated by immunohistochemistry in breast cancer is the need of the hour. This study investigates correlations between the presence of Her2/neu and various clinicopathological prognostic parameters in primary breast carcinomas. OBJECTIVES : 1. Study of the HER2/neu status in breast carcinomas in the study sample. 2. To find the association of HER2/neu status with clinicopathological prognostic parameters in breast carcinomas in the study sample. 3. To find the association of HER2/neu status with lymph node status. METHODOLOGY : Patients diagnosed as carcinoma breast, admitted in Department of General surgery, Govt. Royapettah Hospital and post operative modified radical mastectomy specimens were examined for gross and microscopic features. Immunohistochemistry was used to study the Her2/ neu expression. Her2/neu status was correlated with various clinicopathological prognostic parameters. RESULTS : There was a significant statistical association between Her2/neu expression with lymph node status(p=0.012) and presenting symptoms such as pain and nipple discharge. Expression of Her2/ neu expression was increased in tumour size of more than 2 cms (64%) and higher tumour grade (90%). The major histological subtype was Infiltrating duct carcinoma, NOS type. Meanwhile there was no significant association of Her2/neu expression with menopausal status, NPI groups and other histological parameters. CONCLUSION : Our study data indicates that Her2/neu may be a more powerful predictor for poor prognosis as its expression is associated with important prognostic parameters like increased tumour size, high tumour grade, high NPI score and lymph node involvement.

A bad tumor biomarker is as bad as a bad drug: The gap between genomics data and phenotype to predict response

The search for novel prognostic and predictive parameters in breast carcinoma is relentless. The new technological advances in gene expression profiling and in mutational analysis will hopefully prove to be clinically useful in informing the choice for the systemic therapy. For the time being, we are still relying in established immunohistochemical markers, namely estrogen and progesterone receptors, HER2 and Ki67. Advances in the harmonization of pre-analytical, analytical and interpretative variables may improve accuracy and reproducibility of the results.

Association of Fascin and matrix metalloproteinase-9 expression with poor prognostic parameters in breast carcinoma of Egyptian women.

BackgroundThe effects of fascin on cell invasiveness involve changes in cell motility and matrix metalloproteinase-9 (MMP-9) activity. Previous studies on the prognostic value of fascin and MMP-9 in breast carcinoma revealed conflicting results. To date, no immunohistochemical studies have been performed to assess the possible association between them in breast carcinoma. This study is designed to correlate their expression with prognostic parameters in breast carcinoma and assess the relationship between them.MethodsImmunohistochemical expression of fascin and MMP-9 was evaluated semi quantitatively in 67 cases of breast carcinoma regarding the percentage of positive cells. Chi square test and Fisher’s exact test were used to examine the relationship between categorical variables. Kappa statistics was used to compute the measure of agreement between two investigational methods.ResultsFascin and MMP-9 expressions were detected in 43.28% and 50.75% of breast carcinomas (respectively). Regarding the normal breast tissue, fascin expression was observed in myoepithelial cells and luminal cells of few ducts and acini. However, normal tissue showed negative MMP-9 expression. A significant relationship was observed between fascin and MMP-9 expression and lymph node metastases (p = 0.001 and 0.002 respectively), advanced tumor stage (p = 0.004 and 0.005 respectively), estrogen receptor negative (p = 0.002 and 0.005 respectively), progesterone receptor negative (p = 0.001 and 0.003 respectively) hormonal status and molecular subtypes (p = 0.0007 and 0.014 respectively). A significant strong agreement was detected between fascin and MMP-9 expression (p = 0.0001). More intense immunostaining of fascin and MMP-9 was observed at the invasive fronts compared with other areas of the tumor. Moreover, a significant moderate agreement between fascin and MMP-9 was found regarding the site of predominant intensity.ConclusionFascin and MMP-9 proteins are associated with parameters of poor prognosis in breast cancer. The significant strong agreement between the two markers supports the role of fascin in cell invasiveness by activating matrix proteases besides increasing cell motility. Both proteins may represent potential therapeutic targets for patients with breast cancer especially those with hormone receptor–negative status.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1421167695121127.

HER2 genetic heterogeneity in breast carcinoma

AimsTo determine the frequency of HER2 genetic heterogeneity according to the recent American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) definition (2009) in invasive breast carcinoma,...

Breast cancer multifocality, disease extent, and survival

The prognostic information implied in subgross morphologic parameters such as lesion distribution (unifocal, multifocal, or diffuse) and disease extent in breast cancer has remained largely unexplored in the literature. We aimed to test whether these parameters influence survival in breast carcinoma. The parameters were assessed in a series of 574 cases, all documented in large-format histology sections. We used Cox proportional hazards regression accompanied by Kaplan-Meyer survival curves, with P < .05 regarded as significant. The invasive component was unifocal in 62% (311/499), multifocal in 24% (122/499), and diffuse in 5% (26/499) of the cases. Combining the in situ and invasive tumor components resulted in 48% (274/574) unifocal, 25% (141/574) multifocal, and 20% (117/574) diffuse tumors. Sixty percent (347/574) of the tumors were categorized as having limited extent (occupying an area <40 mm in largest dimension) and 29% (164/574) as extensive. Highly significant (P < .0001) differences were observed in 10-year disease-specific cumulative survival among the cases with unifocal, multifocal, and diffuse invasive (89.6%, 76.0%, and 63.6%, respectively) and combined (92.3%, 82.3%, and 75.7%, respectively) lesion distribution. Patients with extensive tumors exhibited a significantly lower cumulative survival (P < .0001) compared with those with limited extent (91.6% and 75.5%) and a statistically significantly 1.89-fold (95% confidence interval, 1.07-3.37; P = .03) risk for breast cancer death after controlling for tumor attributes, type of surgery, and adjuvant therapy. The hazard ratio for breast cancer death for mutifocal and/or diffuse tumors versus unifocal ones was 1.96 (95%; 1.11-3.48; P = .02) after controlling for the same factors. Lesion distribution and disease extent represent important independent survival-related prognostic parameters in breast carcinoma.

CD44+/CD24− Cells Are Transit Progenitors and Do Not Determine the Molecular Subtypes and Clinical Parameters in Breast Carcinomas

CD44+/CD24− cells have been associated with breast cancer stem/progenitor cell features. However, the status of this phenotype cells in normal, benign and malignant breast tissues has not been studied, and the clinical correlation of this subpopulation in breast cancer is not fully understood. The present study sought to identify these cells in a series of normal, benign, and malignant breast tissues and explore their correlation to the molecular subtypes of breast carcinoma and conventional pathological features. Double-staining immunohistochemistry (DIHC) of CD44 and CD24 was performed on 30 normal breast tissues, 30 breast fibroadenomas (FA), 60 breast invasive ductal carcinomas (IDC), and 3 breast cancer cell lines (MCF-7, MDA-MB-468, and MDA-MB-231). In the normal breast tissues and FAs, three phenotypes were observed including CD44+/CD24+, CD44+/CD24−, and CD44−/CD24− cells. In the IDCs, CD44−/CD24+ cells were detected, in addition to the three aforementioned phenotypes. The strong positive rate (+++, incidence >60%) of CD44+/CD24− was significantly increased from normal breast tissue, FAs to IDCs (0.0%→6.7%→21.7%). However, the CD44+/CD24− cells didn’t correlate with ages of patients, lymph node metastasis, tumor size, molecular subtypes, and the expression of ER, PR, HER-2, PS2, Bcl-2, nm23. The proportion of CD44+/CD24− cells in MCF-7, MDA-MB-468, and MDA-MB-231 was about 1, 5, and 80%, respectively. The results indicate that the CD44+/CD24− cells are transit progenitors and have no association with the molecular subtypes and clinicopathological parameters in the IDCs.