Distribution of CXCR4 and tumour-infiltrating lymphocytes in breast cancer subtypes; their relationship with each other, axillary lymph node involvement, and other prognostic indicators.

We have investigated the distribution of chemokine receptor 4 (CXCR4) and CD8-positive, tumour-infiltrating T lymphocytes (CD8+ TILs) in breast cancer subtypes and explored the relationship between them and the well-established conventional prognostic markers, including axillary lymph node involvement. A total of 250 breast cancer patients were included in the study. The patients were separated into luminal A+B, HER2 enriched/overexpressed (HER2+), and triple- negative, on the basis of their staining characteristics, via conventional staining methods. Immunohistochemical (IHC) staining for CXCR4 and CD8+ TILs were performed on the archival tissues from each patient. With increasing intensity of CXCR4 staining, there was a higher incidence of lymph node metastasis (p < 0.01). Similarly, there was a positive correlation between the primary tumour size, HER2+ subtype, lymphovascular invasion, and axillary lymph node involvement. Dense lymphocytic infiltration was observed in HER2+ and triple-negative patients. No correlation between CD8+ TILs in all sites and breast cancer subtypes was discovered. A reverse correlation was discovered with CD8+ TILs stained only intratumorally and CXCR4 expression. In conclusion, lymph node involvement correlates with higher CXCR4 expression in all breast cancer subtypes. Conversely, no such correlation is found with CD8+ TILs.

Chemokine CXCR-4 and cyclooxygenase-2 in the pathogenesis of pterygium

Background/aim: This study aimed to investigate the expression of chemokine receptor 4 (CXCR-4) and cyclooxygenase-2 (COX-2) in the epithelium and stroma of pterygium tissue in comparison with healthy conjunctiva. Materials and methods: The expression of CXCR4 and COX-2 was investigated by immunohistochemistry in the epithelium and stroma of the pterygium tissue of 29 eyes and compared with healthy conjunctival tissues. The correlation between CXCR4 and COX-2 expression as well as the correlation of these markers with the area of pterygium were evaluated statistically. Results: COX-2 staining scores were 1.75 ± 0.63 in the epithelium and 1.20 ± 0.62 in the stroma of the pterygium tissue. Mean CXCR-4 staining in the epithelium was 0.069 ± 0.37, whereas it was 5.0 ± 2.84 cells in the stroma. There was almost no staining of COX-2 and CXCR4 in the control samples. There was a strong positive correlation between the expression of CXCR-4 and COX-2 in the stroma of the pterygium. Conclusion: CXCR-4 and COX-2 may play important roles in the pathogenesis of pterygium.

Associations between epidermal growth factor receptor and topoisomerase II-alpha gene copy number variations, human papillomavirus positivity, and cytologic analysis in cervical cell lesions.

BACKGROUND: Cervical cancer is the second most common gynecologic cancer worldwide. Human papillomavirus (HPV) infection is a leading etiological factor in cervical carcinoma.The aim of this study was to compare HPV positivity, EGFR and TOP2A gene copy number variations and cervical cytologic findings. MATERIALS AND METHODS: The study group comprised 100 female volunteers between 21-64 years old. Cytologic analysis was performed using the liquid-based cytology technique. HPV DNA testing was performed in all cases. Copy number variations that belong to EGFR and TOP2A genes evaluated by using FISH analysis. RESULTS: Cytologic analysis of the cervical samples revealed abnormal findings in 13 of the 100 study subjects. ASCUS , LSIL, HSIL were determined in 8, 2 and 3 cases respectively as the result of cytologic analysis on all cases. Forty-one (41%) of the 100 women were HPV-positive. Chi-square analysis confirmed that HPV-positive women showed significantly more abnormal cytology (P = 0.035). EGFR deletion, TOP2A deletion and both EGFR and TOP2A deletion were determined in 1, 8 and 1 cases respectively. We found no statistical difference in abnormal cytologic findings between subjects with these gene deletions and subjects with normal gene copy numbers (P > 0.05 for both). No cases of amplification were determined for either gene. CONCLUSION: As a result, HPV positivity and the determination of changes that may occur in the gene copy number in patients with abnormal cytology can be an important tool on account of prognosis. Research with more patients may be suggested.

The Influence of Chemokine CXCR4 and Cyclooxygenase-2 in the Recurrence of Pterygium.

PURPOSE: To investigate the role of CXCR4 and cyclooxygenase-2 in pterygium recurrence. METHODS: A total of 18 primary and 9 recurrent pterygium samples were analyzed. Immunohistochemical staining using primary antibodies against cyclooxygenase-2 and CXCR4 was performed. The cyclooxygenase-2 and CXCR4 expressing cells were calculated separately on the epithelium and stroma. In addition, a correlation between the area of pterygium and CXCR4 and cyclooxygenase-2 levels was investigated. RESULTS: In the primary pterygium group, cyclooxygenase-2 staining was more intense in the epithelium and more dominant in the stroma of the recurrence samples. The CXCR4 expression was more intense in the stroma of both groups. The highest CXCR4 expression was observed in the recurrent pterygium group. There was a strong correlation between the area of pterygium and CXCR4 and cyclooxygenase-2 of stroma. CONCLUSIONS: CXCR4 and cyclooxygenase-2 may play an important role in the recurrence of pterygium.

Comparison between resveratrol and cabergoline in preventing ovarian hyperstimulation syndrome in a rat model.

OBJECTIVE: The aim of this study is to investigate the effects of resveratrol in a rat model of ovarian hyperstimulation syndrome (OHSS) and compare with cabergoline. DESIGN: Randomized controlled, animal study. ANIMAL(S): Female Wistar rats. MATERIAL AND METHODS: A rat OHSS model was used to investigate the effects of resveratrol compare with cabergoline administration for preventing OHSS. Body weight, ovary weight, diameter, vascular permeability (VP), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) expression (immunohistochemistry), and serum estradiol (E2) levels were then compared. RESULTS: The ovarian VEGF concentration was significantly increased in the OHSS Groups (Groups 3-5) compared with the control groups (1 and 2). But vascular permeability, VEGF, and COX-2 expressions were reduced in animals treated with the resveratrol group compared with the cabergoline group (group 5) and the severe OHSS (group 3) group. Blood E2 levels were decreased in group treated with the resveratrol group compared with the cabergoline group (group 5) and severe the OHSS (group 3) group. CONCLUSION(S): Our results in a rat model suggest that resveratrol has a beneficial effect on OHSS by reducing the increases in ovarian daimeter, VP, and VEGF expression associated with OHSS. These effects may be mediated by the COX-2 inhibitory capacity of resveratrol.

[A Gossypiboma (Textiloma) Mimicking a Gastrointestinal Stromal Tumor: A Case Report]. / Gastrointestinal Stromal Tümörü Taklit Eden Gossypiboma (Tekstiloma): Olgu Sunumu.

Gossypiboma (textiloma) is a rare but preventable complication occurring due to oblivion of the surgical material during an operation that carries important diagnostic difficulties as well as high morbidity and mortality risks. The actual incidence is unknown because of its medicolegal aspects. Our case is a 36-years-old female patient, who had a caesarean section two years ago in another center. Clinical examination and radiological investigations gave the impression of "gastrointestinal stromal tumor" and the surgically taken out mass was sent to our pathology department. The case was reported as a "gossypiboma"' and presented here to emphasize the diagnostic difficulties in the preoperative period, the life-threatening nature of the condition and as well as the rarity of the reported cases.

Comparison of the effects of letrozole and cabergoline on vascular permeability, ovarian diameter, ovarian tissue VEGF levels, and blood PEDF levels, in a rat model of ovarian hyperstimulation syndrome.

OBJECTIVE: To evaluate the effects of letrozole and cabergoline in a rat model of ovarian hyperstimulation syndrome (OHSS). STUDY DESIGN: In this prospective, controlled experimental study, the 28 female Wistar rats were divided into four subgroups (one non-stimulated control and three OHSS-positive groups: placebo, letrozole, and cabergoline). To induce OHSS, rats were injected with 10 IU of pregnant mare serum gonadotropin from day 29 to day 32 of life, followed by subcutaneous injection of 30 IU hCG on day 33. Letrozole rats received with a single dose of 0.1 mg/kg letrozole via oral gavage, on the hCG day. Cabergoline rats received with a single dose of 100 µg/kg cabergoline via oral gavage, on the hCG day. All animals were compared in terms of body weight, vascular permeability (VP), ovarian diameter, ovarian tissue VEGF expression (assessed via immunohistochemical staining), and blood pigment epithelium-derived growth factor (PEDF) levels. RESULTS: The OHSS-positive placebo group (group 2) exhibited the highest VP, ovarian diameter, extent of VEGF staining, and lowest PEDF level, as expected. No significant difference was evident between the letrozole and cabergoline groups in terms of any of body weight; VP; PEDF level; ovarian diameter; or the staining intensity of, or percentage staining for, VEGF in ovarian tissues. CONCLUSIONS: Letrozole and cabergoline were equally effective to prevent OHSS, reducing the ovarian diameter, VP, and PEDF and VEGF levels to similar extents.

Sirenomelia: a review of embryogenic theories and discussion of the differences from caudal regression syndrome.

OBJECTIVE: To discuss the pathological features of sirenomelia in the light of our 10 cases and review the current theories. METHODS: We identified 10 patients with sirenomelia from our hospital database. All clinical details and the autopsy features of 10 cases were noted. RESULTS: Of the 10 children with sirenomelia seven had bilateral renal agenesis, three had bladder agenesis and one had a renal hypoplasia. Single umbilical artery was found in 60% of children with sirenomelia. External genitalia was ambiguous in seven of 10 patients. CONCLUSIONS: Even though the etiology of caudal regression syndrome (CRS) and sirenomelia remains unknown we tend to believe that sirenomelia and CRS might be different entities.

The Role of Parafibromin, Galectin-3, HBME-1, and Ki-67 in the Differential Diagnosis of Parathyroid Tumors.

OBJECTIVES: Parathyroid carcinoma (PC) is a rare parathyroid tumor compared to parathyroid adenoma (PA) and atypical parathyroid adenoma (APA). Recent studies have suggested parafibromin has a role in the differential diagnosis of parathyroid tumors. We sought to determine the role of parafibromin as well as galectin-3, Ki-67, and HBME-1 as diagnostic markers in the differential diagnosis of parathyroid tumors. METHODS: A total of 92 cases diagnosed with PA, APA, or PC at Sifa University and Private Ege Pathology Laboratory between 2006-2012 were included in the study. Parafibromin (microarray), galectin-3, Ki-67, and HBME-1 were evaluated using immunohistochemistry in all parathyroid tumors. RESULTS: Eighty-four cases were diagnosed with PA, six with APA, and two with PC. The study group consisted of 82 females and 10 males. Their mean age was 50.9 years, and the mean tumor diameter was 1.97 cm. Parafibromin was negative in the two PC cases but positive in all APA and PA cases. Positivity was observed with galectin-3 in 17 adenoma cases, three atypical adenomas, and two carcinoma cases. Positivity with HBME-1 was found in 26 PA cases and one PC case. Parafibromin and galectin-3 expression was significant between the three tumor groups but not for HBME-1 expression. Parafibromin expression increased in PA whereas galectin-3 expression decreased. A statistical significance was found between the three tumor groups according to the Ki-67 score (p=0.010). Additionally, the Ki-67 proliferation index was under 1% in PAs. CONCLUSION: The number of PCs in our series was small so our data mostly reflects the immunohistochemical characteristics of PAs. Parafibromin expression, galectin-3 negativity, and a Ki-67 proliferation index under 1% were estimated as beneficial in the differential diagnosis of difficult parathyroid tumors.

Montelukast is effective in preventing of ovarian hyperstimulation syndrome; an experimental study.

OBJECTIVES: To determine the efficacy of montelukast in comparison with cabergoline in the prevention of ovarian hyperstimulation syndrome (OHSS) in rats. MATERIAL AND METHODS: An experimental OHSS model was formed in 35 female Wistar rats. Rats (22 days old) were randomized into 5 groups, each containing 7 animals. The control group received no therapy; the mild OHSS group was administered pregnant mare serum gonadotropin (PMSG) 10 IU for 4 days, hCG 10 IU on the 5th day; the severe OHSS group received PMSG 10 IU for 4 days, hCG 30 IU on the 5th day The montelukast group: received montelukast 10 mg/kg/day and the cabergoline group was administered cabergollne 100 microg/kg/day via oral gavage for 6 days (days 22-27), in addition to those of severe OHSS. All groups were sacrificed on 28th day Body weight, ovarian diameter and weight, vascular permeability vascular endothelial growth factor (VEGF), semiquantitative VEGF receptor-1, and VEGF receptor-2 (VEGFR-2) immunohistochemistry were evaluated. RESULTS: Ovarian diameter and VEGF expression were significantly lower in the montelukast and cabergoline groups than in the severe OHSS group. While montelukast was more effective in limiting vascular permeability in the severe OHSS, cabergoline was superior to montelukast with respect to the limiting effect on increased body weight and VEGFR-2 expression. CONCLUSIONS: The VEGF/VEGFR-2 interaction plays an important role in OHSS pathogenesis. Montelukast limits VEGF expression, and cabergoline reduces both VEGF and VEGFR-2 expressions; they are both effective therapies for the prevention of severe OHSS.

The Effects of Cyclin D1 and Bcl-2 Expression on Aggressive Behavior in Basal Cell and Basosquamous Carcinoma.

BACKGROUND AND OBJECTIVE: Clinical behavior of basal cell carcinoma (BCC) is known to be different according to histological growth pattern and basosquamous cell carcinomas (BSC) are known with their aggressive behavior and metastatic capacity. In this study, we evaluated bcl-2 and cyclin D1 expressions in BCC and BSC cases comparatively, to explore their predictive value on the aggressive behavior of these tumors. METHODS: One hundred tumors belong to 92 patients diagnosed as basal cell carcinoma and basosquamous carcinoma were studied. Basal cell carcinomas were classified as aggressive and non-aggressive types according to growth pattern. Number of Cyclin D1 and bcl-2 positive cells in immunohistochemically stained serial sections were scored as low (0-1 +) and high (2 and 3+) in all tumors. RESULTS: A statistically significant difference was found between non-aggressive (nodular type) and aggressive types (micronodular, infiltrative types and BSC) for these markers ( P <0.005). Cyclin D1 was higher in the aggressive group, while bcl-2 was lower in the aggressive group compared to the non-aggressive group. CONCLUSION: Higher Cyclin D1 and lower bcl-2 scores was correlated with aggressive tumor types and these results could be used as markers to predict aggressive behavior in BCC and BSCs.

Myo-inositol is a promising treatment for the prevention of ovarian hyperstimulation syndrome (OHSS): an animal study.

PURPOSE: To evaluate the efficacy of myo-inositol (MI) pretreatment in OHSS. METHODS: In this experimental OHSS rat model, 42 immature Wistar albino female rats were divided into 6 groups: (1) the control group, (2) the ovarian stimulation group, (3) the OHSS group, (4) the OHSS + Metformin group, (5) OHSS + MI group, (6) OHSS + Metformin + MI group. OHSS was established after treatment with metformin and myo-inositol for 14 days, in the meanwhile the treatment of metformin and myo-inositol was also continued. All animals were killed 48 h after hCG administration and were compared in terms of vascular permeability, ovarian weight and diameter, ovarian VEGF, COX-2 and PEDF expression (immunohistochemistry), serum PEDF and estradiol (E2) levels. RESULTS: Vascular permeability, VEGF and COX-2 expressions were reduced in animals treated with MI and/or metformin. While PEDF expression was increased in the groups taking metformin, there was no difference in PEDF expression in the group taking MI and OHSS group. There was no significant difference in serum PEDF levels between groups. Blood E2 levels were decreased in groups treated with MI or metformin compared to the OHSS group. CONCLUSIONS: Our data demonstrate that myo-inositol is effective in preventing OHSS, similar to metformin. Although the two drugs are thought to act through distinct mechanisms, there is no apparent benefit to co-treatment with both drugs in an animal model of OHSS. Administration of myo-inositol prior to IVF treatment may favor the control of ovulation induction. Further studies are necessary to elucidate the mechanism of action and further support our findings.

Does uterine prolapse alter endometrial cyclooxygenase 2 expression and promote the development of premalignant lesions?

OBJECTIVE: The aim of this study was to evaluate the expression of cyclooxygenase 2 (COX-2) and its association with the development of premalignant lesions in gland structures of the endometrium in patients with uterine prolapse, a condition which exposes the uterus to mechanical and infectious stress. METHODS: The study included 102 patients who underwent hysterectomy to correct grade 3-4 uterine prolapse and 105 patients who underwent hysterectomy for other causes. Endometrial gland structures underwent immunohistochemical staining and COX-2 expression was graded. Grades 0 and 1 represent low expression; grades 2 and 3 correspond to high levels of COX-2 expression. RESULTS: The prevalence of grade 2-3 COX-2 expression was significantly higher in the endometrial gland structures of patients with prolapse and hyperplasia compared to the remaining patients (p = 0.014). Grade 0-1 COX-2 expression was significantly more common in the endometrial gland structures of patients without uterine prolapse or hyperplasia (p = 0.004). Among the patients without endometrial hyperplasia, COX-2 expression was elevated in the endometrial gland structures of those with uterine prolapse compared to those without prolapse. CONCLUSION: Elevated COX-2 expression may explain the presence of unexpected premalignant lesions of the endometrium in patients with uterine prolapse.

Prophylactic vitamin D supplementation in ovarian hyperstimulation syndrome: an animal study.

PURPOSE: To investigate the effect of vitamin D in ovarian hyperstimulation syndrome (OHSS). METHODS: In this animal study, 28 immature female Wistar rats were divided into four groups: group 1 (control); group 2 (ovarian stimulation); group 3 (OHSS group); group 4 (OHSS + vitamin D group). All groups were killed 48 h after hCG administration and were compared in terms of vascular permeability, ovarian weight, ovarian diameter, vascular endothelial growth factor (VEGF) expression (immunohistochemistry) in ovarian tissue and pigment epithelium-derived factor (PEDF) level in the serum (ELISA test) with the Kruskal-Wallis and Mann-Whitney U tests. RESULTS: VEGF expression in the vitamin D group was similar to that in the OHSS group. However, the PEDF level was significantly higher in the vitamin D group (p = 0.013). CONCLUSIONS: Prophylactic vitamin D supplementation is not sufficiently effective in preventing OHSS. Vitamin D effectively increases PEDF, which has an opposing effect on VEGF, which plays a key role in OHSS. Thus, the protective effect of Vitamin D on OHSS should be investigated with a vitamin D deficient model in the study group.

Management of Cyclosporine and Nifedipine-Induced Gingival Hyperplasia.

Gingival enlargements modified by medications are becoming more common because of the increased use of inducing drugs, and may create speech, mastication, tooth eruption, periodontal, and aesthetic problems. We hereby present a case of a 54-year-old man with 12-month history of generalized gingival enlargement in the keratinized gingiva was referred to our clinic. The patient had a history of kidney transplant and was under medication of cyclosporine and nifedipine. After medical consultation, cyclosporine was changed to tacrolimus and nifedipine was changed to captopril. Gingivectomy was performed using a diode laser, and scaling and root planning were performed. At five months postoperative, the gingival enlargements relapsed and diode laser-assisted surgery was repeated. The patient was followed-up on second postoperatively at 18 months and no relapse was seen. Diode laser-assisted gingivectomy was found to be useful for coagulation during surgery and decreased postoperative bleeding. Recurrence risk of cyclosporine and nifedipine-induced gingival overgrowth is high, thus, there is a great need for prolonged care of patients following treatment and prosthetic restoration.

CXCR-4 and COX-2 expression in basal cell carcinomas and well-differentiated squamous cell carcinomas of the skin; their relationship with tumor invasiveness and histological subtype.

OBJECTIVE: Both CXCR-4 and COX-2 are biological markers that play a significant role in several neoplastic processes. We explored the differences in expression of these markers in certain subtypes of basal cell carcinoma, and squamous cell carcinomas in general. MATERIAL AND METHOD: In this study, we investigated the differences between 38 patients with basal cell carcinoma (nodular, infiltrative and micro-nodular subtypes) and 24 patients with well-differentiated squamous cell carcinomas with respect to their depth of invasion, tumor location, age, and CXCR-4 and COX-2 expression. RESULTS: Statistically, we found no significant difference between squamous cell carcinomas and basal cell carcinoma in terms of CXCR-4 and COX-2 expression; however, the degree of marker expression became stronger with increasing depth of invasion in both tumors. The expression of both markers was also higher in infiltrative type basal cell carcinoma compared to all the other subtypes. The results were statistically significant (p<0.05). Additionally, a significantly positive correlation also existed between COX2 and CXCR4 expression (p < 0.05). CONCLUSION: The degree of expression of CXCR-4 and COX-2 is related to invasiveness in both malignancies; thus, infiltrative type of basal cell carcinoma displays the highest degree of CXCR-4 and COX-2 expression among all the subtypes. Furthermore, our results indicate that these two biological markers may both be involved in the process of carcinogenesis and require investigation with further molecular and genetic studies in larger series.

Synchronous Primary Endometrial Carcinoma and Metastatic Malignant Melanoma in an Ovarian Cystic Teratoma.

Malignant transformation of a benign cystic teratoma of the ovary is only rarely seen. A review of the English literature revealed no reports of a malignant melanoma developing from concurrent primary endometrial carcinoma and ovarian cystic teratoma. We report herein a 54-year-old nulliparous woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for a pelvic mass and was diagnosed by histopathological examination to have a malignant melanoma developing from concurrent primary endometrial carcinoma and ovarian cystic teratoma. No foci of primary malignant melanoma except for the ovary were found upon clinical examination. The patient received postoperative interferon alpha 2B and radiotherapy. She was still asymptomatic at 12 months of follow-up.