Kemal Kürşat Bozkurt

The clinicopathological and prognostic significance of CD24, CD44, CD133, ALDH1 expressions in invasive ductal carcinoma of the breast: CD44/CD24 expression in breast cancer.

BACKGROUND Recently, there are several studies about cancer stem cells (CSC), indicating that they are the cells that initiate the tumor, provide progression, metastasis and responsible for the aggressive tumor behavior. MATERIALS AND METHODS The purpose of this study is to investigate the expressions of CD24, CD44, their different combinations, ALDH1 and CD133 in invasive ductal carcinoma. Their relationships with clinicopathologic parameters, such as tumor grade, lymphovascular invasion, tumor size, axillary lymph node involvement, stage, hormone receptors, HER2 expression, basal like tumors, triple negative status and prognosis were also investigated. Tissue microarray method was used to investigate ımmunohistochemical CD24, CD44, ALDH1 and CD133 expressions in 105 invasive ductal carcinoma cases. RESULTS CD133 expression was significantly associated with tumor size (p=0.023) and stage (p=0.009). CD133 expression was decreased in tumors with larger tumor size, higher stage and lymphovascular invasion. CD133 expression was positively correlated with CD44 (r=0.212, p=0.032) and CD44(+)/CD24(+) (r=0.202, p=0.040) expressions. CD44, CD24 and ALDH1 expressions showed no significant relationship and correlation with clinicopathologic features. There was a significant relationship (p=0.048) between CD44(+)/CD24(-/low) phenotype and basal like tumors. EGFR expression was positively correlated with CD44(+)/CD24(-/low) phenotype (r=0.211, p=0.036). CONCLUSIONS Basal like tumors are enriched for CSCs with CD44(+)/CD24(-/low) phenotype. CD133 can detect a different population of CSC in breast carcinoma.

The relation of radiation-induced pulmonary fibrosis with stress and the efficiency of antioxidant treatment: an experimental study.

Background Radiation-Induced Lung Injury has 2 components: radiation pneumonitis and radiation fibrosis. The pulmonary fibrosis has no known efficient treatment. The purpose of this study was to study the relationship between the oxidant/antioxidant status and pulmonary fibrosis in rats having radiation induced pulmonary fibrosis and to study the antioxidant effects of pentoxifylline, vitamin E, and vitamin C in the treatment of pulmonary fibrosis. Material/Methods The study rats were divided into 5 groups: Thoracic RT + vitamin E+ Pentoxifylline for group 1, Thoracic RT + vitamin C + Pentoxifylline for group 2, Thoracic RT + vitamin C + vitamin E + Pentoxifylline for group 3, and Thoracic RT + Pentoxifylline for group 4, and group 5 was the control group. Results When groups are evaluated in pairs, significant differences between group 1 and 2, group 1 and 4, and group 1 and 5 were determined (p: 0.002, p: 0.002, p<0.001, respectively). No significant difference was determined between group 1 and 3 (p: 0.161). No significant difference was determined between group 2 and group 3, 4, and 5 (p: 0.105, p: 0.645, p: 0.234, respectively). There was no significant difference between group 4 and 5 (p: 0.645). Conclusions The combination of vitamin E and pentoxifylline is efficient in preventing radiation-induced lung fibrosis. The additional benefit of vitamin C, which is added to this combination to increase the antioxidant activity, cannot be shown. It would be useful to investigate the combination of vitamin E, pentoxifylline, and other non-enzymatic antioxidants.

Investigation of immunohistochemical ERα, ERβ and ERβcx expressions in normal and neoplastic breast tissues.

Estrogen receptor alpha (ERα) is a well-established prognostic marker in breast cancer. The role of estrogen receptor beta (ERβ) in breast cancers is still under investigation. We aimed to investigate the clinicopathological significance and immunohistochemical expression patterns of ERα, total ERβ (ERβ) and its spliced variant ERβcx in normal breast, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Our study population comprised 10 normal breasts, 26 DCISs and 44 IDCs. Immunohistochemical expression of these markers was investigated in sections of formalin-fixed, paraffin-embedded blocks by 2 observers. In invasive ductal carcinomas, ERβ expression had a significant positive correlation with ERα expression (p=0.013), while ERβcx expression was significantly associated with the presence of lymphovascular invasion (p=0.046). There was a significant relationship between ERα expression and low histological grade (p<0.0001). Similarly, ERα+/ERβ+ tumors (p=0.004) and ERα+/ERβcx+ tumors (p=0.008) were significantly associated with low histological grade, too. ERα expression (p=0.009), ERβcx expression (p=0.048) and ERα+/ERβ+ coexpression (p=0.002) increased significantly in progression from normal breast to invasive ductal carcinoma. Expression of ERα correlates with less aggressive phenotypic features, and ERβ expression is positively correlated with ERα expression in breast cancer. ERβcx is associated with aggressive features and can take part in the progression of invasive carcinoma. Increase in ERα+/ERβ+ coexpression, ERα expression and ERβcx expression in breast cancer progression indicates an enhancement in ER expressions or an alteration in expression patterns of different ER variants during mammary carcinogenesis.

Immunohistochemical COX-2 overexpression correlates with HER-2/neu overexpression in invasive breast carcinomas: A pilot study

Cyclooxygenase-2 (COX-2) is a prostaglandin synthase that catalyzes the synthesis of prostaglandin G2 and H2. It has been shown that COX-2 plays an important role in tumorigenesis of different tumor types and it is thought to take part in breast carcinogenesis. In the present study, we aimed to investigate the relationship of immunohistochemical COX-2 expression with clinicopathological parameters, including HER-2/neu overexpression in invasive breast carcinoma (IBC). Our study population comprised 10 normal breasts, 25 ductal carcinomas in situ (DCIS), and 51 invasive breast carcinomas. Immunohistochemical overexpressions of COX-2 and HER-2/neu were investigated in sections of formalin-fixed, paraffin-embedded blocks by 3 observers. In normal breast, DCIS and IBC, the COX-2 overexpression rate was 0%, 84%, and 58.8%, respectively. In IBC, COX-2 overexpression had a significant relationship with HER-2/neu overexpression (p=0.026) and a high histological grade (p=0.026). COX-2 expression in both DCIS (n=25) and IBC (n=51) was significantly higher than in normal breast tissue (p<0.0001). In addition, the COX-2 expression rate was significantly higher in DCIS than in IBC (p=0.042). Our results indicated that COX-2 overexpression correlates with aggressive phenotypic features, such as HER-2/neu overexpression and high histological grade in IBC. Increased expression of COX-2 in both DCIS and IBC in comparison to normal breast could indicate a role in breast carcinogenesis. COX-2 overexpression may provide a clinically useful biomarker for estimating tumor aggressiveness.

The relation of beclin 1 and bcl-2 expressions in high grade prostatic intraepithelial neoplasia and prostate adenocarcinoma: a tissue microarray study.

The aim of the present study was to evaluate the expressions of beclin 1 and bcl-2 in prostate cancer (PC) and high grade prostatic intraepithelial neoplasia (HGPIN), and to investigate their relationship with clinicopathological parameters. The study included 30 benign prostatic hyperplasia (BPH), 40 HGPIN and 106 primary PC cases. The expressions of beclin 1 and bcl-2 were assessed semiquantitatively based on both the percentage and intensity of positive staining cells. Beclin 1 was positive in 27 (90%) BPH, 37 (92.5%) HGPIN, and 90 (84.9%) PC cases (p>0.05). Bcl-2 immunostaining was detected in 99 (93.4%) PC, 37 (92.5%) HGPIN, and 9 (30%) BPH cases (p<0.0001). Regarding expression scores, beclin 1 was significantly lower in PC cases than in the HGPIN and BPH groups (p<0.0001), and it was also negatively correlated with Gleason score (p=0.004, r=-0.274). Bcl-2 expression score was significantly higher in PC than in the other groups (p<0.0001), and also positively correlated with Gleason score (p<0.0001, r=0.425). Furthermore, a negative correlation was found between bcl-2 and beclin 1 expression scores in PC cases (p=0.006, r=-0.265). Our results suggest an association between bcl-2 and beclin 1 expressions in malignant transformation of prostate tissue and also in regulating PC cell differentiation, progression and the aggressiveness of PC.

Increased expression of COX-2 in recurrent basal cell carcinoma of the skin: A pilot study

INTRODUCTION Basal cell carcinoma (BCC) is the most frequent malignant skin tumor. BCC rarely metastasizes, but it is often locally aggressive. Cyclooxygenase-2 (COX-2) is critical for tumor formation, angiogenesis and metastasis. Matrix metalloproteinases (MMPs) are the members of the family of zinc (Zn)- and calcium-dependent endopeptidases that degrade the extracellular matrix. MATERIALS AND METHODS In our study, we used immunohistochemical methods for the evaluation of COX-2, MMP-2 and MMP-9 expression in tissue samples of 30 primary and 10 recurrent skin BCC cases. RESULTS Immunohistochemical COX-2 expression was significantly higher in the infiltrating pattern of BCC compared with the nodular (P = 0.005) and superficial (P = 0.041) subtypes in the primary BCC group. There was not a significant difference between nodular and superficial BCCs for COX-2 expression. In addition, COX-2 expression was significantly higher in the recurrent BCC group than in the primary BCC group (P = 0.030). There was no statistically significant difference between the histological subtypes of primary BCCs and between primary and recurrent BCCs for MMP-2 and MMP-9 expressions. CONCLUSIONS Our data confirm previous findings that COX-2 and MMP-9 expressions are increased in BCC. Our results revealed an elevated COX-2 expression in recurrent BCCs. We suggest that COX-2 inhibition might have beneficial effects in BCCs, especially for the tumors with a higher level of COX-2 expression or aggressive phenotype.

Expression of NGF, GDNF and MMP-9 in prostate carcinoma

The aim of the present study was to investigate the immunohistochemical expression of NGF, GDNF and MMP-9 in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PC), and to analyse their association with the clinicopathological parameters in PC cases. Immunohistochemistry was performed on the tissue microarray (TMA) sections of 30 BPH, 40 HGPIN and 121 primary PC tissues. There was a significant difference regarding the expression of NGF and GDNF between PC and HGPIN (p<0.0001; p<0.0001), and PC and BPH (p=0.001; p<0.0001), but not between HGPIN and BPH (p>0.05). Furthermore MMP-9 expression was significantly different among all groups (PC vs. HGPIN, p<0.0001; PC vs. BPH, p<0.0001; HGPIN vs. BPH, p=0.001). NGF, GDNF and MMP-9 expression was significantly stronger in cases with high Gleason score (p<0.0001, p=0.004, p<0.0001 respectively) and pT stage (p=0.046, p=0.004, p=0.001, respectively) in PC cases. All these markers were also associated with perineural, lymphovascular and extraprostatic invasion (p <0.05). In addition, a positive correlation was found between NGF and MMP-9 (p<0.0001, r=0.435), NGF and GDNF (p<0.0001, r=0.634), and GDNF and MMP-9 (p<0.0001, r=0.670) in PC cases. According to our results we suggest an interaction between NGF, GDNF and MMP-9 during the transition to malignancy in PC. Also this interaction may involve in regulating PC cell differentiation, tumor invasion, progression, and the agressiveness of PC.

The role of immunohistochemical adrenomedullin and Bcl-2 expression in development of type-1 endometrial adenocarcinoma: Adrenomedullin expression in endometrium.

BACKGROUND Adrenomedullin (AM) is a pluripotent peptide first discovered from human pheochromocytoma. AM expression has been shown in various cancer types including endometrium cancer. Bcl-2 is an antiapoptotic protein which might be regulated by AM in hypoxic conditions. The aim of the present study was to investigate the role of AM and Bcl-2 expressions in carcinogenesis of type-1 endometrium cancer. MATERIALS AND METHOD Study group consisted of 10 proliferative endometrium, 22 simple endometrial hyperplasia, 23 endometrial intraepithelial neoplasia (EIN) and 30 Grade 1 endometrioid adenocarcinoma patients. AM and Bcl-2 expressions were investigated by immunohistochemistry. RESULTS Mean AM Allred score was 3±2.6, 5.6±1.6 and 5.7±2.5 in benign, EIN and adenocarcinoma groups, respectively. AM expression was significantly higher in EIN and adenocarcinoma groups than in benign endometrium group (p<0.05). Mean Bcl-2 Allred score was 6.4±2.1, 5.2±2.6, 2.3±2 in benign endometrium, EIN and adenocarcinoma groups, respectively. Mean Bcl-2 Allred score was similar between benign endometrium and EIN groups (p>0.05). However, it was significantly lower in adenocarcinoma group (p<0.05). An inverse correlation between AM and Bcl-2 expressions was found (r: -0.4, p<0.001). CONCLUSIONS Our findings showed that AM expression increased in progression from benign endometrium to EIN and type-1 adenocarcinoma while expression of Bcl-2 decreased in transition from EIN to carcinoma.

Placental-site trophoblastic tumor and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography.

OBJECTIVE Pre-operative imaging characteristics of placental site trophoblastic tumor (PSTT) are variable and non-specific. Although magnetic resonance imaging (MRI), ultrasonography, chest CT and X-rays findings have been studied the fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) findings of PSTT have not been previously documented. We present the findings of a first case of PSTT evaluated by pre-operative ¹⁸F-FDG PET/CT. A suspicious mass was biopsied and revealed PSTT in post-operative pathological examination. She was referred to the gynecology-oncology department. The ¹⁸F-FDG PET/CT scan revealed a 27 x 20 mm laterally expanded lesion that showed increased ¹⁸F-FDG uptake (SUVmax: 5.20) on the right isthmus of the uterus. The ¹⁸F-FDG PET/CT findings were in accordance with those from chest X-ray/s, CT and pelvic ultrasonography. A systematic, nerve sparing, paraaortic and pelvic lymph node dissection along with total hysterectomy and salpingoopherectomy was performed. The patient was discharged uneventfully. CONCLUSION ¹⁸F-FDG PET/CT scan was able to identify the mass in the uterus which was shown by pathology to be PSTT. This finding of PET/CT was in accordance with other imaging techniques. Lymphatic mapping of ¹⁸F-FDG PET/CT in this case was also in accordance with surgery and pathology findings.

Primary Extra-Gastrointestinal Stromal Tumor of Mesenteric Root: a Rare Version of a Soft Tissue Tumor Located on a Critical Region

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract albeit an annual incidence of 11 per million people, and it accounts for 1% of primary gastrointestinal malignancies. GISTs are thought to originate from the interstitial cell of cajal, which is a pace-maker cell that regulates the gastrointestinal tract motility [1]. GISTs may arise anywhere in the alimentary tract; stomach (50–60%), small bowel (30–35%), colorectum (5%), and esophagus (<1%). GISTs arising as primary tumors outside the gastrointestinal tract compromise <5% of all GISTs and are called extra-gastrointestinal stromal tumor (EGIST) [2]. The most common site of EGIST is omentum. Mesenteric and retroperitoneal EGIST is very rarely reported [2, 3]. Small-bowel mesentery (SBM) root, that is contiguous with the pararenal spaces, extends diagonally from its origin at the Treitz ligament inferiorly and toward the ileocecal valve. The root of SBM is surgically a strategic location due to major vessels; superior mesenteric artery (SMA) and superior mesenteric vein (SMV) [4]. Therefore, surgical treatment of EGIST in mesenteric root may be different from other EGIST/GIST. Besides, prognosis and outcome of the disease may also be different. To our knowledge, 14 primary mesenteric EGIST has been reported in English literature until now [5]. Aim of the study is to report a huge mesenteric root EGIST that is located in a critical anatomical region and discuss treatment options and oncological outcomes.