Prognostic Importance of Tumor Deposits in the Ipsilateral Axillary Region of Breast Cancer Patients.

Tumor deposits (TD) are irregular discrete tumor masses in adipose tissue, discontinuous from the primary tumor, that are described in various cancers. The incidence and/or prognostic value of TD in breast carcinomas have not been studied so far. We reevaluated 145 breast cancer patients, diagnosed and treated between 2001 and 2006 at our institution for the presence and incidence of TD. Histologic type, grade, size of the primary tumor, estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 status of the tumor, and presence of peritumoral lymphovascular invasion were included in the data. TD were detected in 42 cases (29.0%). The mean age of the patients was 52.2 years (27-82). Most patients (79.3%) had either invasive carcinoma of no special type (NST) or invasive lobular carcinoma, and most tumors (86.9%) were either grade 2 or 3. After excluding TD from the number of metastatic lymph nodes, the pN status of 9 patients changed. Univariate analysis of 110 patients with follow-up information revealed that the new pN status (p = 0.036), presence of local recurrence (p = 0.016) and TD (p = 0.003) were significantly correlated with distant metastases. The median follow-up of the patients was 84 months (5-161), 10-year disease-free survival and overall survival were 67.2% and 73.7%, respectively. In multivariate analysis, presence of TD remained independently associated with distant metastasis (p = 0.002). The probability of distant metastasis was 3.3 times higher in patients with TD. These results emphasize that TD are present in breast cancer patients, and that their presence should warn the clinician in terms of possible distant metastasis. Therefore, presence of TD, the evaluation of which is neither time consuming nor require sophisticated methods, should be included in pathology reports.

Immunohistochemical HER2 Status Evaluation in Breast Cancer Pathology Samples: A Multicenter, Parallel-Design Concordance Study.

OBJECTIVE: As patients with increased human epidermal growth factor receptor (HER2) overexpression are more likely to benefit from trastuzumab treatment, the accuracy of HER2 receptor status in breast cancer patients is significant for appropriate disease management. However, this assessment is not harmonized and results may be highly variable between centers. The aim of this study was to investigate the degree of interlaboratory variability in the results of HER2 expression reported by 5 participating centers and to assess the concordance between these centers and a reference laboratory.Materials and Methods: A total of 30 breast cancer samples were tested and scored for HER2 expression using immunohistochemical method in 5 centers from Turkey and in a reference laboratory from Netherlands (Academic Medical Center, Amsterdam). All the participating centers had an experience of more than 10 years regarding the HER2 testing. The results were compared both among the centers and with the reference laboratory. RESULTS: When the concordance of participating centers and the reference laboratory was evaluated regarding negative (0-1+), equivocal 2(+) and positive 3(+) classification of HER2 immunostaining, the highest concordance was found in Center-A, and the lowest in Center-C (Kendall's tau-b concordance coefficient 0.911 and 0.724, respectively). The concordance of the centers with reference laboratory was 80.0% both in equivocal and positive samples, while it increased up to 91.8% in negative samples. CONCLUSIONS: This study showed that in general there is sufficiently good agreement between the reference laboratory and the participating centers for immunohistochemical HER2 assessment.

Angiocentric Glioma: The Infiltrative Glioma with Ependymal Differentiation.

Angiocentric glioma is an epileptogenic, infiltrative, low grade glial tumor, with ependymal and astrocytic differentiation, most commonly seen in young adults and the pediatric age group. Herein we report a case of 21-year-old male patient who presented with fever and pharmaco-resistant seizures. Computed tomography revealed an iso-dense mass lesion in the gyrus rectus of the left frontal lobe. On magnetic resonance imaging the mass was hyperintense on both T1- and T2-weighted images with no contrast enhancement. Histopathological examination revealed monomorphous tumor cells diffusely infiltrating the neuropil with circumferential, radial, or longitudinal angiocentric alignment and subpial aggregation with perpendicular alignment of the cells to the pial surface. Among central nervous system tumors with ependymal differentiation, this distinct entity is the one with an infiltrating growth pattern. In spite of the infiltrating pattern, it does not seem to have a potential for aggressive behavior.

Transition to Virtual Microscopy in Medical Undergraduate Pathology Education: First Experience of Turkey in Dokuz Eylül University Hospital.

OBJECTIVE: Pathology education includes an important visual part supporting a wide range of theoretical knowledge. However, the use of traditional microscopes in pathology education has declined over the last decade and there is a lack of interest for microscopy. Virtual microscopy, which was first described in 1985 and has experienced a revolution since 2000, is an alternative technique to conventional microscopy, in which microscopic slides are scanned to form digital images and stored in the web. The aim of this study was to evaluate the use of virtual microscopy in practical pathology sessions and its effects on our students and undergraduate education at our faculty. MATERIAL AND METHOD: Second and third year medical students who were used to conventional microscopes were included in the study. The practical sessions were carried out via virtual slides and the effect of the new technique was investigated by a scale at the end of each session. Academic staff from the pathology department joined sessions to promote discussion and respond to questions. Student ratings were analysed statistically. RESULTS: The evaluation of the ratings showed that the students were easily adapted to the use of virtual microscopy. They found it user-friendly and thought that the opportunity of viewing slides at home was advantageous. Collaboration between students and interactive discussions was also improved with this technique. CONCLUSION: It was concluded that the use of virtual microscopy could contribute to the pathology education of our students.

Efficacy and safety of breast radiothermometry in the differential diagnosis of breast lesions.

AIM OF THE STUDY: The aim of this study is to research the contribution of radiothermometry (RTM) to the characterization of breast masses, the differentiation of malignant-benign masses and diagnosis of early stage breast cancer. MATERIAL AND METHODS: This prospective study comprised 182 cases of patients diagnosed with a breast mass and a control group of 55 cases: a total of 237. RESULTS: When histopathology is accepted as the gold standard among diagnostic methods, the sensitivity, specificity, and positive-negative predictive value for RTM were 90.9%, 20.8%, 61.2% and 62.5%, respectively. Consistency was 0.129. When compared with mammography the same values for RTM examination are 87%, 81.4%, 58% and 95.5%. Consistency was 0.582. Evaluating with respect to size of the mass accepting mammography as the gold standard, RTM examination had sensitivity, specificity, positive and negative predictive values for masses 2 cm and above of 88.9%, 83.3%, 88.9% and 83.3%. Consistency was 0.722. The consistency of RTM for lesion diagnosis in BI-RADS II breast structure is higher than the consistency of mammography. CONCLUSIONS: Identification of lesions in the breast and presence of microcalcification by RTM shows that it is more trustworthy compared to mammography. When compared with mammography the validity results for RTM show there is a good level of conformity between the two methods. When evaluated based on the area below the ROC cure and compared to mammography, RTM is sufficiently successful at evaluating positive and negative cases.

In situ hybridization analysis of invasive breast carcinomas with immunohistochemically negative Her-2 status (a national multicenter study).

OBJECTIVE: The aim of this study was to determine the rate of Her-2 gene amplification in breast cancer cases with a previous negative Her-2 result as determined by immunohistochemistry (score 0 or 1). MATERIAL AND METHOD: 552 cases of invasive breast carcinoma were assessed with the contribution of 9 centers. Previous immunohistochemistry score was either 0 or 1+ in all cases. These cases were re-tested by Her-2 silver in situ hybridization in the central laboratory. Her-2 gene amplification was defined as Her-2/CEP 17 ratio of more than 2.2. Cases with a ratio between 1.8 and 2.0 were defined as equivocal and cases with a ratio of less than 1.8 were defined as negative. RESULTS: Re-testing of the 552 cases with silver in situ hybridization showed a total of 22 cases with Her-2 gene amplification, of which 11 (3.2%) were found to be score 0, and 11 were found to be score 1+ (5.3%) by immunohistochemistry previously. Her-2 gene amplification rate of cases (score 0 and 1+) ranged from 0% to 10.48% among the centers. Polysomy was found in 28 (8.1%) of the score 0 cases and 25 (12.1%) among the score 1+ cases. Five (9.4%) of the cases with polysomy were found to be amplified, and 48 (90.6%) were not. CONCLUSION: The results of the study show that a group of cases (3.98%) with a potential to benefit from anti-Her-2 therapy may be missed with the immunohistochemical method. This indicates the importance of quality assurance, especially in central laboratories with many breast cancer cases in daily practice.

Diagnosis, treatment characteristics, and survival of women with breast cancer aged 65 and above: a hospital-based retrospective study.

BACKGROUND: Breast cancer incidence in women increases with age, while survival rates decrease. Studies interpret this result as meaning higher comorbidity, diagnosis at later stages of the disease, and less effective treatment in the elderly. The aim of this study is to evaluate the diagnosis and treatment characteristics of breast cancer and their effect on the survival of women aged 65 and above. METHODS: The data within the files of 1064 women with breast cancer, who were followed-up in Dokuz Eylul University Medical Faculty Hospital between 2000 and 2006, were reviewed retrospectively. The survival probabilities at years 1 and 5 were calculated by life table analysis. The Kaplan-Meier test was used for calculating mean survival time, and the differences between groups were evaluated by log-rank test. The backward elimination method was used for multivariate analysis, and a -2 log-likelihood ratio was used for comparison of different models. RESULTS: Of the patients, 25.3% were aged 65 and above at the time of the diagnosis. Patients in this group had more comorbidities and were more likely to be diagnosed at advanced stages than younger patients. Additionally, they had lower rates of surgical treatment, chemotherapy or radiotherapy. One and 5-year survival probabilities among age groups were 96.1% and 84.5%, respectively, for <65 years, 93.5% and 84.8%, respectively, for 65-69, 98.7% and 84.0%, respectively, for 70-74, and 85.5% and 59.6%, respectively, for 75 years and above. In the multivariate model, age, clinical stage, and comorbidity were found to be negatively associated with the survival rate. CONCLUSIONS: The survival of women with breast cancer aged 65 and above was affected negatively by age at diagnosis, clinical stage, and the presence of comorbidity. Early diagnosis also is very important for elderly women. Additionally, because of higher comorbidity, their evaluation and treatment should be planned by an interdisciplinary team.

Warthin-like papillary carcinoma of the thyroid: a case series and review of the literature.

Warthin-like tumor of the thyroid is a recently described rare variant of thyroid papillary carcinoma. The distinguishing histological feature of this variant is papillary foldings lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. Its prognosis has been reported to be almost similar to conventional papillary carcinoma. In this case series, we report four cases with Warthin-like papillary carcinoma of the thyroid, diagnosed at Dokuz Eylul University Faculty of Medicine Department of Pathology in 2008 and 2009. Three patients were female. The mean patient age was 39 years (range, 20-56) and the mean tumor size was 1.7 cm (range, 0.9-2.0 cm). All of the cases had lymphocytic thyroiditis in the background. None of the tumors showed lymphovascular invasion. The patients are free of any recurrence and/or distant metastasis with a mean follow-up of 25 months. This rare variant of thyroid papillary carcinoma with distinct histopathological features should be indicated in pathology reports. Further studies and long-term follow-up of patients are needed to highlight the biological behavior of this variant.

Invasive micropapillary carcinoma of the breast: a clinicopathologic study of 103 cases of an unusual and highly aggressive variant of breast carcinoma.

Invasive micropapillary carcinoma (IMPC) of the breast is an uncommon, highly aggressive breast cancer that may occur in pure and mixed forms. Our aim in this study is to investigate the relationship between clinical, histopathologic, and immunohistochemical features of pure and mixed IMPC cases diagnosed and treated at our institution. One hundred and three IMPC cases diagnosed at our institution over a period of 19 years have been selected. Clinical, histopathologic features, as well as hormone status and c-erb-B2 overexpression of tumors were re-evaluated. Mann-Whitney U, chi-squared, Kaplan-Meier, and Fisher's exact tests were used for statistical analyses. Results were considered to be significant at p < 0.05. Twenty cases (19.4%) were pure, and 83 cases (80.6%) were mixed IMPC. The most common nonmicropapillary invasive carcinoma component in mixed cases was invasive ductal carcinoma (IDC; 78.3%). Progesterone receptor was significantly less positive in pure IMPC cases (p = 0.031). There was no statistically significant difference between the two groups, in terms of mean age of the patients (53.0 versus 52.8), mean tumor size (26.6 mm versus 27.7 mm), presence of high-grade tumor (p = 0.631), presence of sentinel lymph node (SN) metastasis (p = 1.000), axillary lymph node metastasis (p = 1.000), lymphatic invasion (p = 1.000) and blood vessel invasion (p = 0.475), c-erbB-2 overexpression of tumor cells (p = 0.616), distant metastasis (p = 0.549), or overall survival (p = 0.759). The local recurrence rate of the two groups was not statistically significant either (16.7% versus 4.3%). However, local recurrence was detected 12% more commonly (p = 0.100), and ~8 months earlier (p = 0.967) in pure IMPC cases, compared to mixed cases. In addition, presence of local recurrence was found to be statistically significantly associated with estrogen receptor (ER) status (p = 0.004), progesterone receptor (PR) status (p = 0.001), and c-erb-B2 overexpression (p = 0.016) in all patients. Overall survival rate was significantly associated with ER staining of the tumor (log-rank = 0.028). Our findings suggest that hormone receptor negativity may explain the more aggressive behavior of pure IMPC compared to mixed cases. Besides, longer survival period of patients with ER positivity, and the relationship of hormone status and c-erb-B2 overexpression and local recurrence further support favorable prognostic value of hormone receptors in invasive breast cancer.

Early biventricular molecular responses to an acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) remains as one of the most common lethal diseases in the world and therefore it is necessary to understand its effect on molecular basis. Genome-wide microarray analysis provides us to predict potential biomarkers and signaling pathways for this purpose. OBJECTIVES: The aim of this study is to understand the molecular basis of the immediate right ventricular cellular response to left ventricular AMI. MATERIAL AND METHODS: A rat model of left anterior descending coronary artery ligation was used to assess the effect of left ventricular AMI on both the right ventricle as a remote zone and the left ventricle as an ischemic/infarct zone. Microarray technology was applied to detect the gene expression. Gene Ontology and KEGG pathways analysis were done to identify effected pathways and related genes. RESULTS: We found that immune response, cell chemotaxis, inflammation, cytoskeleton organization are significantly deregulated in ischemic zone as early response within 30 min. Unexpectedly, there were several affected signaling pathways such as cell chemotaxis, regulation of endothelial cell proliferation, and regulation of caveolea regulation of anti-apoptosis, regulation of cytoskeleton organization and cell adhesion on the remote zone in the right ventricle. CONCLUSION: This data demonstrates that there is an immediate molecular response in both ventricles after an AMI. Although the ischemia did not histologically involve the right ventricle; there is a clear molecular response to the infarct in the left ventricle. This provides us new insights to understand molecular mechanisms behind AMI and to find more effective drug targets.

Validation of three breast cancer nomograms and a new formula for predicting non-sentinel lymph node status.

BACKGROUND: The aim of the study was to evaluate the available breast nomograms (MSKCC, Stanford, Tenon) to predict non-sentinel lymph node metastasis (NSLNM) and to determine variables for NSLNM in SLN positive breast cancer patients in our population. MATERIALS AND METHODS: We retrospectively reviewed 170 patients who underwent completion axillary lymph node dissection between Jul 2008 and Aug 2010 in our hospital. We validated three nomograms (MSKCC, Stanford, Tenon). The likelihood of having positive NSLNM based on various factors was evaluated by use of univariate analysis. Stepwise multivariate analysis was applied to estimate a predictive model for NSLNM. Four factors were found to contribute significantly to the logistic regression model, allowing design of a new formula to predict non-sentinel lymph node metastasis. The AUCs of the ROCs were used to describe the performance of the diagnostic value of MSKCC, Stanford, Tenon nomograms and our new nomogram. RESULTS: After stepwise multiple logistic regression analysis, multifocality, proportion of positive SLN to total SLN, LVI, SLN extracapsular extention were found to be statistically significant. AUC results were MSKCC: 0.713/Tenon: 0.671/Stanford: 0.534/DEU: 0.814. CONCLUSIONS: The MSKCC nomogram proved to be a good discriminator of NSLN metastasis in SLN positive BC patients for our population. Stanford and Tenon nomograms were not as predictive of NSLN metastasis. Our newly created formula was the best prediction tool for discriminate of NSLN metastasis in SLN positive BC patients for our population. We recommend that nomograms be validated before use in specific populations, and more than one validated nomogram may be used together while consulting patients.

Microporous polysaccharide hemospheres and seroma formation after mastectomy and axillary dissection in rats.

OBJECTIVE: Seroma is the most common complication after breast surgery. Several methods have been proposed to prevent seroma, but none of these provided a significant effect. A prolonged wound healing process is the most important cause of seroma. Microporous polysaccharide hemospheres (MPH) are used to achieve hemostasis. They may also accelerate wound healing. In this study, the effects of MPH on seroma formation were investigated. MATERIAL AND METHODS: Female Wistar rats weighing between 200 g and 250 g were used. There were eight rats in each of the control and study groups. Right breast mastectomy and axillary dissection were performed in all rats. While no application was performed after the operation in the control group, MPH was locally applied to the surgical site in the study group. Ten days after the operation, seroma fluid was aspirated and the total volume was recorded. The aspirates were analyzed and tissue samples were obtained from the surgical site. RESULTS: Seroma was significantly lower in the study group (p=0.001). The mean albumin and lactate dehydrogenase levels were significantly lower in the study group (p=0.003). Pathological examination revealed that increase in fibrous tissue was significantly greater in the control group (p=0.032). CONCLUSION: MPH may reduce seroma after mastectomy.

Predicting the likelihood of nonsentinel lymph node metastases in triple negative breast cancer patients with a positive sentinel lymph node: Turkish Federation of Breast Disease Associations protocol MF09-01.

BACKGROUND: Triple negative (TN) tumor has a relatively high rate of recurrence and distant metastasis, but results of studies revealed that triple positive tumor is an independent predictor of axillary lymph node involvement. Our aim was to evaluate the frequency of nonsentinel lymph node metastasis (NSLNM) involvement in operable TN breast cancer with positive sentinel lymph node (SLN) and predicting the likelihood of NSLNM in this cohort of patients by using 4 different nomograms. METHODS: A total of 128 patients with TN and SLN(+) underwent complete axillary lymph node dissection in 14 different centers in Turkey. For comparison, we used our previous multicenter MF08-01 Protocol, which identified 441 patients with estrogen receptor (ER(+)) who had a positive SLN biopsy and underwent subsequent complete axillary lymph node dissection. Turkish, Cambridge, and Stanford nomograms and the Tenon Score system were used to calculate the probability of NSLNM. RESULTS: Patients with TN tumor had a larger tumor size. The actual percentage of NSLN positivity was 41% in the TN group and 47.1% in patient with ER(+). The Tenon Score was ≤3.5 in 12% of patients with TN and ER(+); the area under the curve in the receiver operating characteristics curve were 0.53 and 0.59, respectively. Based on the Turkish, Cambridge, and Stanford nomograms, areas under the curve were 0.54, 0.53, and 0.61, respectively in patients with TN, and were 0.79, 0.72, and 0.70, respectively, in patients with ER(+). CONCLUSION: Using the Tenon Score system underestimates NSLN positivity, and tested nomograms are not good discriminators of NSLNM in patients with TN and positive SLN.

Factors predicting non-sentinel lymph node involvement in sentinel node positive breast carcinoma.

OBJECTIVE: In routine practice, axillary lymph node dissection is performed in early invasive breast cancer patients with positive sentinel node biopsy. However, sentinel node is the only involved axillary node in 40-70% of patients, and determining factors that predict axillary non-sentinel node involvement will therefore prevent unnecessary axillary lymph node dissection and decrease morbidity. MATERIAL AND METHOD: In this study, 119 invasive breast cancer patients with sentinel node metastasis who underwent axillary lymph node dissection between 1998-2009 at our institution were studied. Primary tumor characteristics and features of the metastatic tumors in sentinel nodes, such as microanatomic location, size of metastasis, and the ratio of metastatic tumor area to the total sentinel node area were evaluated. Student's t-test and multivariate logistic regression were used for statistical analysis. RESULTS: The mean age of the patients was 50.7 years (28-80). Forty-three patients (36%) had invasive ductal and 25 patients (21%) had invasive lobular carcinoma. Most of the patients had either pT1 (44%) or pT2 (54%) tumors. Fifty-four patients (45%) had no further positive nodes in the axilla. The metastatic deposits in the sentinel node were subcapsular in 16 patients (13%). The percent area of sentinel node occupied by tumor (p < 0.001), number of sentinel nodes (p=0.041), and microanatomic location of metastatic tumor (p=0.002) were significantly associated with non-sentinel node metastasis in univariate analysis. The percent area of sentinel node occupied by tumor (p < 0.001) and number of sentinel nodes (p=0.033) remained significantly associated with non-sentinel node involvement in multivariate analysis. CONCLUSION: In patients with invasive breast cancer and positive sentinel node, area percent of sentinel node occupied by tumor, and the number of sentinel nodes removed are independently predictive of non-sentinel node involvement.

Cystic fibroadenoma of the breast: a case report.

Fibroadenoma is the most common breast tumor in adolescent and young women. Fibroadenomas that consist of sclerosing adenosis, papillary apocrine metaplasia, epithelial calcifications, and/or cysts greater than 3 mm are considered as complex fibroadenoma. The relative risk of developing breast cancer in patients with complex fibroadenoma is increased, compared to women with noncomplex fibroadenoma. Extensive cystic degeneration in a fibroadenoma, so called "cystic fibroadenoma" is very rare. Herein, we present a case of such a lesion in a 43-year-old female who has been on follow-up for fibrocystic changes of the breast, and discuss both radiological and histopathologic differential diagnosis of this lesion with other cystic lesions of the breast, including cystic papilloma. The patient is free of disease after 17 months of clinical follow-up.

Incidence of thyroid dysfunction and thyroid cancer in renal transplant recipients: a single center experience.

BACKGROUND: The prevalence of thyroid cancer in renal transplant population has not been widely studied, and there is no consensus on the management of thyroid cancer in transplant patients. The aim of this study was to evaluate changes in thyroid hormone levels and investigate the incidence of the thyroid cancer after renal transplantation. MATERIALS AND METHODS: From October 1989 to April 2007, 122 renal allograft recipients that were being followed underwent thyroid ultrasonography to determine nodules together with thyroid hormone levels. Ultrasound-guided fine-needle aspiration biopsy (FNAB) was performed to the nodules > 10 mm or those with 8-10 mm diameter but with calcifications. RESULTS: One hundred and eight patients (88.5%) had normal thyroid function. None of the patients had overt hypothyroidism, 2 had subclinical hypothyroidism, 10 subclinical thyrotoxicosis, and 2 low T3 syndrome. Mean thyroid volume was 14.2 +/- 7.2 ml. In all, 91.8% was diagnosed with goiter (n = 112). Seventy-two thyroid nodules were detected in 49 kidney allograft recipients (single nodule in 30, multiple in 19 patients). Eighty-four biopsy samples were reported as benign (n = 21, 87.5%), 8 as suspicious (n = 2, 8.3%), and 4 as inadequate (n = 1, 4.1%). After surgery, one of the patients (0.8%) with suspicious FNAB was reported as papillary thyroid carcinoma. CONCLUSION: Because of the high incidence of thyroid dysfunction in transplant patients, screening of thyroid function should be a part of follow-up. Our results suggest that although frequency of nodules is increased in kidney transplant patients, prevalence of thyroid cancer is slightly, but not significantly, higher than that of the normal population.

Predicting invasive phenotype with CDH1, CDH13, CD44, and TIMP3 gene expression in primary breast cancer.

We aimed to determine changes in the expression of the genes CDH1, CDH13, CD44, and TIMP3 to look for any relationship between them, HER2 and ESR1 expression at the RNA level, and the histopathological properties of tumors. We also analyzed the expression properties of double-negative (estrogen receptor [ER] and human epidermal growth factor receptor [HER2] both negative) breast tumors. Expression status was studied in fresh tissue at the mRNA level with quantitative PCR using hydrolysis probes. Sixty-two cancer patients and four normal controls were included in the study. When the tumor group was analyzed as a whole, the correlations of ESR1 with CDH1, CDH13, and TIMP3 were P < 0.05, P < 0.005, and P < 0.005, respectively. In ER-positive tumors, CDH1 and CDH13 were correlated directly (P < 0.005) when HER2 was correlated with CDH1, CDH13, and TIMP3 indirectly (P < 0.005, P < 0.005, and P < 0.05, respectively). CDH1 and CD44 had a strong indirect correlation (P < 0.005) in ER-negative tumors. There were significant differences in the expression levels of the CDH13, TIMP3, and CD44 genes (P < 0.005, P < 0.005, and P < 0.05, respectively) between the ER-positive and -negative groups. All four genes were found to be correlated with invasive properties in both ER-positive and -negative tumors. In double-negative tumor samples, only CD44 had a significant and strong correlation with stage, lymph node involvement, and metastasis (P < 0.05, P < 0.005, and P < 0.05, respectively). As a conclusion, a decrease in CDH1, CDH13, and TIMP3 expression levels with an increase in CD44 can be used as an indicator for invasion in both ER-positive and -negative breast tumors. In double-negative tumor tissues, CD44 can be considered a marker for aggressive properties.

Pathologic nipple discharge in patients with radiologically invisible mass: review of 28 consecutive sub-areolar explorations.

The carcinoma frequency of clinically and radiologically negative pathologic nipple discharges (PNDs) and the optimum management strategy of these cases are still unclear. In this study, the frequency of cancer and the situation of the classic surgical intervention in patients with PND and invisible mammographic and ultrasonographic results are reviewed. The data pertaining to the cases of sub-areolar exploration and major duct excision in a surgery clinic of university hospital from December 2002 to June 2007 have been examined in detail. In 28 cases with PND, which did not have any findings during conventional radiologic examinations, 21% of cases had malignant, and 7% of cases had atypical ductal hyperplasia. The frequency of invasive or in situ carcinoma is not low in clinically and radiologically negative PNDs. Sub-areolar exploration and major duct excision seems to be an appropriate and definitive diagnostic and therapeutic option in this special patient group.