Ali Ibrahim Sevinc

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.

Improvement of Colonic Healing by Preoperative Rectal Irrigation With Short-Chain Fatty Acids in Rats Given Radiotherapy

BACKGROUNDWe investigated the effect of preoperative rectal irrigation with short-chain fatty acids on irradiated colonic anastomosis in rats.METHODSSixty male Wistar rats were divided into four groups. Group I (control group, n = 15) underwent left colon resection and primary anastomosis. Group II (Short-chain fatty acids pretreatment group, n = 15) had short-chain fatty acids rectal irrigation for five days preoperatively. Group III (preoperative radiotherapy group, n = 15) underwent irradiation to the whole pelvis eight and four days before the operation, for a total dose of 20 Gy. Group IV (preoperative radiotherapy group + short-chain fatty acids pretreatment group, n = 15) had rectal irrigation with short-chain fatty acids for five days after the second irradiation. Within each group, animals were anesthetized to assess the clinical, mechanical, histologic, and biochemical parameters of anastomotic healing on either the third or seventh postoperative days.RESULTSThe mean bursting pressure was significantly low in Group III on Day 3 and was significantly high in Group IV on Day 7 (P = 0.001, P = 0.021). The burst occurred at the anastomoses in all animals tested on the third postoperative day, and outside of the anastomoses in all animals tested on the seventh postoperative day. The histologic parameters of anastomotic healing, such as epithelial regeneration and formation of granulation tissue, were significantly improved by use of preoperative rectal irrigation with short-chain fatty acids on Day 7. The amount of total and salt-soluble collagen concentrations significantly increased in Group IV compared with the control group on Day 3 (P = 0.008, P = 0.004).CONCLUSIONSome mechanical and histologic aspects of colonic anastomotic healing can be adversely affected by preoperative radiotherapy, but rectal irrigation with short-chain fatty acids may improve anastomotic healing.

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.

Beneficial Effect of Endocrinologist-Performed Ultrasonography on Preoperative Parathyroid Adenoma Localization

OBJECTIVE To evaluate whether endocrinologist-performed ultrasonography improves the localization of parathyroid adenomas in patients with primary hyperparathyroidism. METHODS We performed a retrospective analysis of consecutive patients with primary hyperparathyroidism due to a single adenoma who underwent surgery at the Dokuz Eylul University Hospital in Izmir, Turkey, between January 2000 and January 2008. Data regarding the localization of adenomas were obtained from surgical reports. Neck ultrasonography was performed in all patients as first-line imaging. Parathyroid ultrasonography was performed by a staff radiologist between January 2000 and December 2004. Beginning January 2005, parathyroid ultrasonography was performed blindly by an endocrinologist in addition to the staff radiologist. In the case of discordant preoperative localization between the endocrinologist- and radiologist-performed ultrasonography, surgery was performed according to the technetium Tc 99m sestamibi (MIBI) scan and endocrinologist-performed ultrasonography localization results. RESULTS A total of 156 patients with primary hyperparathyroidism due to a single adenoma were included. Of the 156 patients, 139 also underwent MIBI scan. Ultrasonography localized 102 parathyroid adenomas (65%). The accuracy of the ultrasonography was improved in patients who underwent endocrinologist-performed ultrasonography. Endocrinologist-performed ultrasonography localized the adenoma correctly in 19 patients for whom the staff radiologist had reported a negative or unsuccessful localization. When ultrasonography results were combined with the MIBI scan findings, parathyroid adenomas were again more likely to be localized in patients who underwent operation after January 2005 and thus had endocrinologist-performed ultrasonography. CONCLUSION Our results suggest that endocrinologist-performed ultrasonography improves the preoperative localization of parathyroid adenoma.

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.

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.

Differentiation between Phyllodes Tumors and Fibroadenomas Based on Mammographic Sonographic and MRI Features.

Background: This study was performed to compare the mammographic, sonographic, and magnetic resonance imaging (MRI) characteristics of phyllodes tumors and fibroadenomas, which may resemble each other. Methods: Preoperative mammograms, B-mode and Doppler sonograms, and dynamic breast MRIs of 72 patients with pathologically proven fibroadenomas and 70 patients with pathologically proven phyllodes tumor were evaluated in this retrospective study. Statistical significance was evaluated using chi-square and Fishers exact tests. Correlations in lesion size among radiological methods were examined by Pearsons correlation analysis. Results: The features that differed on mammogram were size, shape, and margin of the mass. Sonograms showed significant differences in size, shape, margin, echo pattern, and vascularization of the mass. Pearsons correlation analysis showed strong agreement among radiological methods in terms of assessment of size. Tumor size ≥ 3 cm, irregular shape, microlobulated margins, complex internal echo pattern, and hypervascularity were significant findings of phyllodes tumors. Internal cystic areas on MRI were frequently associated with phyllodes tumors. Conclusion: Mammographic, sonographic, and MRI findings of fibroadenomas and phyllodes tumors could help radiologists to ascertain imaging-histological concordance and guide clinicians in their decision making regarding adequate follow-up or the necessity of biopsy.