Serdar Saydam

DNA copy number changes detected by comparative genomic hybridization and their association with clinicopathologic parameters in breast tumors

The purpose of this study was to use comparative genomic hybridization (CGH) to screen breast tumors for copy number changes: 22 ductal, 9 lobular, 7 mixed, 2 micropapillary carcinomas, and 2 ductal carcinoma in situ were studied and various regional genomic imbalances were detected. The majority of the aberrations identified in this study were in line with previous CGH findings. The most frequent DNA sequence copy number changes were 1q, 8q, and 20q gains. The frequency of 16q losses was significantly higher in lobular carcinomas. The nodal involvement was 10 times higher in cases showing losses of 13q than in cases having normal peak profile at this region. Estrogen receptor positivity was significantly higher in cases displaying 20q gains and 16q losses. Unambiguous high-level DNA amplifications have also been detected. These mapped to 4q31, 6q21 approximately q22, 8q21 approximately q24, 8p11.2 approximately p12, 11q13, 15q24 approximately qter, 20q13.1 approximately qter, and 20q12 approximately qter chromosomal locations. Our results highlight several chromosomal regions that may be important in the molecular genetics of distinct clinicopathologic breast cancer subgroups.

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. (Cancer Sci 2009; 100: 2341–2345)

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 Fishers 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.

Seroma Prevention by Using Corynebacterium parvum in a Rat Mastectomy Model

Seroma formation is the most common complication after mastectomy and continues to be an important problem during the early postoperative period. Several surgical and medical methods have been developed to try to overcome this problem; however, so far none have been used successfully in the routine clinical practice. The aim of this study is to evaluate the effects of Corynebacterium parvum (CP) as a sclerosing agent in both prevention and treatment of seromas after mastectomy and axillary dissection in an animal model. Sixty female Sprague-Dawley rats underwent mastectomy and axillary dissection under general anaesthesia. Following surgery, the rats were treated in 1 of 3 ways. In the prevention group, 1 cm3 (0.35 mg) CP solution was injected beneath the skin flap just before closure of the incision after mastectomy. In the treatment group, animals in which a seroma was formed, the fluid was aspirated, and 1 cm3 CP solution was injected beneath the flap. In the control group, animals in which seromas formed, aspiration only was performed. The frequency of seroma formation decreased when CP solution was injected immediately after the operation (p < 0.01). In addition, seroma formation was effectively treated by CP injection when compared with the control group (p < 0.05). CP was effective as a prophylactic agent in the prevention group and as a therapeutic agent in the treatment group in this experimental model. CP injection may be useful for the management of this problem in a clinical setting.

Early and delayed thallium-201 scintigraphy in thyroid nodules: the relationship between early thallium-201 uptake and perfusion.

Seventy-six patients with thyroid nodules were studied. Initially, 74 MBq of thallium-201 was injected. The thyroid gland was imaged 15 min (early) and 3 h (delayed) after the injection. Thereafter, 185 MBq technetium-99m pertechnetate was injected. Immediately after the injection, a 1-min perfusion image was acquired, followed by an image at 20 min. Increased early and delayed201Tl uptake compared with the contralateral thyroid tissue was adopted as the criterion for malignancy. Sensitivity, specificity and negative predictive values were found to be 85%, 64% and 78%, respectively, in operated patients, but these values were 86%, 87% and 95%, respectively, in the whole group, including patients followed with fine-needle aspiration biopsy. With the purpose of investigating the relationship between perfusion and early201Tl uptake, both perfusion and early images were graded comparing nodular activity with contralateral thyroid activity. There was a poor correlation between perfusion and201Tl uptake. The correlation was even worse in hyperactive nodules. It is concluded that early and delayed201Tl imaging should not be used in the differential diagnosis of cold nodules and that early201Tl uptake seems to be more closely related to factors other than perfusion.

Papillary carcinoma arising in subhyoid ectopic thyroid gland with no orthotopic thyroid tissue

Ectopic thyroid gland with no orthotopic thyroid tissue is extremely rare. The authors present a case of a follicular variant of papillary carcinoma developed from an ectopic thyroid gland with no orthotopic thyroid tissue.

A Case of Benign Schwannoma of the Breast: Mammographic, Ultrasonographic and Color Doppler Ultrasonographic Findings

A 61-year-old asymptomatic postmenopausal woman presented to the radiology department for a screening mammogram. The patient’s medical history was noncontributory and her physical examination was within normal limits. Her prior mammogram, 3 years earlier, was normal. The mammogram showed that both breasts were almost entirely composed of fat (Breast Imaging Reporting and Data System [BIRADS] category 1: almost entirely fat breast composition). There was 20 · 10 mm, lobular, circumscribed, high-density mass without microcalcification on one-third posterior of the upper–lower outer quadrant of her left breast (Fig. 1). On ultrasonography, the lesion was well-circumscribed, parallel in orientation, hypoechoic, slightly inhomogeneous, and solid with moderate acoustic enhancement (Fig. 2). On color Doppler sonography, the mass was hypovascular (Fig. 3). No enlarged axillary or supraclavicular lymph nodes were noted. The right breast was normal. Although the mammography and ultrasonography findings indicated that the mass was benign, the patient’s age, hyperdensity of the lesion, and normal prior mammogram were considered as suspicious for malignancy (BIRADS category 4A: a low suspicion for malignancy); thus, a biopsy was recommended. After mammography-guided wire localization, excision was performed. Macroscopically, the excised specimen was measured 4 · 2.5 · 2 cm. The size of the tumor was 1.2 · 1 · 0.5 cm. The tumor was grown in an expansile fashion and was encapsulated. The cut surface was homogenous, gray and tan with irregular yellow areas. Microscopically, the tumor was well encapsulated by the existing epineurium and composed of two main patterns termed Antoni A and Antoni B (Fig 4). The Antoni A pattern consisted of fascicles of fusiform cells with elongate nuclei and indistinct cytoplasmic borders. These cells were often arranged in a palisading pattern and in some areas, bizonal arrangement of such

Warthin-Like Papillary Carcinoma of the Thyroid: A Case Series and Review of the Literature Tiroidin Warthin-Benzeri Papiller Karsinomu: Olgu Serisi ve Literatür Derlemesi

ABSTRACT 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. ÖZ Tiroidin Warthin-benzeri tümörü son dönemlerde tanımlanan, tiroid papiller karsinomunun nadir görülen bir varyantıdır. En önemli histolojik özelliği, nükleer psödoinklüzyonlar içeren berrak nukleuslu onkositik özellikte neoplastik hücrelerle döşeli, santral stromalarında belirgin lenfositik infiltrat bulunan papiller yapılardır. Prognozunun klasik papiller karsinom ile benzerlik gösterdiği bildirilmiştir. Bu olgu serisinde, Dokuz Eylül Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı’nda 2008 ve 2009 yıllarında tanı almış dört Warthin-benzeri papiller karsinom olgusu sunulmuştur. Hastaların üçü kadın olup, ortalama yaş 39 (20-56 yaş), ortalama tümör boyutu 1.7 cm (0,9-2,0 cm) idi. Olguların tümünde zeminde belirgin lenfositik tiroidit izlendi. Olguların hiçbirinde lenfovasküler invazyon görülmedi. Ortalama 25 aylık klinik ve radyolojik izlem sonucu hastaların hiçbirinde rekürrens ya da uzak metastaz saptanmadı. Tiroidin nadir görülen Warthin-benzeri papiller karsinomu, ayırdedici histopatolojik özelliklere sahip olup patoloji raporlarında belirtilmelidir. Bu varyantın biyolojik davranışını açığa çıkarabilmek için ileri çalışmalara ve uzun dönem hasta takiplerine ihtiyaç vardır.

A pilot study for human tumor/DNA banking: returned more questions than answers

A pilot study was performed for setting up the Dokuz Eylül University Breast Tumor DNA Bank (DEUBTB) to facilitate the sharing of tumor DNA/RNA samples and related data from cases collected by collaborators specializing in the breast cancer diseases between 2004 and 2006. The pilot study aimed to provide answers for certain questions on: (1) ethical concerns (informing the volunteer for donating specimen, anonymizing the sample information, procedure on sample request), (2) obtaining and processing samples (technical issues, flowchart), (3) storing samples and their products (storing forms and conditions), (4) clinical database (which clinical data to store), (5) management organization (quality and quantity of personnel, flowchart for management relations), (6) financial issues (establishment and maintenance costs). When the bank had 64 samples, even though it is quite ready to supply samples for a research project, it revealed many questions on details that may be answered in more than one way, pointing that all biobanks need to be controlled by a higher degree of management party which develops and offers quality standards for these establishments.

Pathologic Nipple Discharge in Patients with Radiologically Invisible Mass: Review of 28 Consecutive Sub‐areolar Explorations

Abstract:  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.