Associations between the expression of mucins (MUC1, MUC2, MUC5AC and MUC6) and clinicopathologic parameters of human breast carcinomas.

AIMS: The aim of this study is to evaluate the relationships between the expression of mucins in invasive breast carcinomas and clinicopathologic parameters. MATERIALS AND METHODS: We examined 150 cases of invasive breast carcinoma, using the 2012 World Health Organization (WHO) classification of the tumors of the breast. We studied the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. We also evaluated normal breast tissue and ductal carcinoma in situ (DCIS) lesions in nearby invasive tumor areas. RESULTS: In invasive breast carcinomas, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 98.6%, 11.3%, 9.9, and 8.5% of cases, respectively. MUC2, MUC5AC, and MUC6 were overexpressed in invasive tumors and DCIS lesions were compared with normal breast tissue. The apical pattern of MUC1 was correlated with low grade and ER expression. MUC2 was correlated with mucinous carcinoma and an inverse association with invasive ductal carcinoma, not otherwise specified (NOS). MUC6 expression was associated with lymphovascular invasion. CONCLUSIONS: Most invasive breast tumors express MUC1 and the apical pattern of MUC1 is correlated with low grade and ER expression. MUC6 expression is associated with indicators of poor prognosis. Further comprehensive studies need to evaluate the role of mucins as a potential biomarker and to be used as a specific therapeutic target against breast cancer.

Late-onset amyloidosis cutis dyschromica: an unusual case.

Amyloidosis cutis dyschromica (ACD) is a rare form of primary cutaneous amyloidosis. ACD, first described by Morishima in 1970 is characterized by (i) macular, speckled, reticular hyperpigmentation with hypopigmented spots distributed extensively over the body; (ii) little or no pruritus; (iii) prepubertal onset; and (iv) focal subepidermal amyloid deposition. A 49-year-old woman presented with a 20-year history of progressive, asymptomatic, generalized mottled hyper- and hypopigmented macules all over the body. Histopathological examination of a punch biopsy specimen showed deposition of homogeneous, eosinophilic material in the papillary dermis. This amorphous, eosinophilic material was stained metachromatically with crystal violet stain and found to be compatible with amyloid. Based on the clinical and histopathological findings, the patient was diagnosed as having ACD. Amyloidosis cutis dyschromica must be considered in the differential diagnosis of patients with diffuse dyschromatosis including both hyperpigmented and hypopigmented lesions and histopathological confirmation is necessary in order to reach a correct diagnosis.

The protective effect of Papaverine and Alprostadil in rat testes after ischemia and reperfusion injury

ABSTRACT Objective: To investigate the effect of papaverine and alprostadil on testicular torsion-detorsion injury in rats. Materials and Methods: A total of 40 male Wistar-Albino rats were used in this study. Four hours of right testicular torsion was applied to each group, excluding sham oper- ated group. The torsion-detorsion (T/D), T/D + papaverine and T/D + alprostadil groups received saline, papaverine and alprostadil at the same time as surgical detorsion, respectively. At 14 days after the surgical detorsion, ischaemic changes and the degree of damage were evaluated with Cosentino scoring and the Johnson tubular biopsy score (JTBS). Results: JTBS was determined as 8.8±2.7 in the Sham group, 5.08±1.9 in the T/D+papaverine group, 5.29±2.3 in the T/D +alprostadil group and 2.86±1.9 in the TD group. The JTBS was determined to be statistically significantly high in both the T/D + papaverine group and the T/D + alprostadil group compared to the T/D group (p=0.01, p=0.009). In the T/D + papaverine group, 3 (43%) testes were classified as Cosentino 2, 3 (43%) as Cosentino 3 and 1 (14%) as Cosentino 4. In the T/D +alprostadil group, 5 (50 %) testes were classified as Cosentino 2, 3 (30 %) as Cosentino 3 and 2 (20%) as Cosentino 4. Conclusion: The present study indicated that spermatic cord administration of alprostadil and papaverine showed a protective effect against ischemia/reperfusion injury after right-side testes torsion and histological changes were decreased after testicular ischemia reperfusion injury.

The protective effect of Papaverine and Alprostadil in rat testes after ischemia and reperfusion injury.

OBJECTIVE: To investigate the effect of papaverine and alprostadil on testicular torsion-detorsion injury in rats. MATERIALS AND METHODS: A total of 40 male Wistar-Albino rats were used in this study. Four hours of right testicular torsion was applied to each group, excluding sham operated group. The torsion-detorsion (T/D), T/D + papaverine and T/D + alprostadil groups received saline, papaverine and alprostadil at the same time as surgical detorsion, respectively. At 14 days after the surgical detorsion, ischaemic changes and the degree of damage were evaluated with Cosentino scoring and the Johnson tubular biopsy score (JTBS). RESULTS: JTBS was determined as 8.8±2.7 in the Sham group, 5.08±1.9 in the T/ D+papaverine group, 5.29±2.3 in the T/D +alprostadil group and 2.86±1.9 in the TD group. The JTBS was determined to be statistically significantly high in both the T/D + papaverine group and the T/D + alprostadil group compared to the T/D group (p=0.01, p=0.009). In the T/D + papaverine group, 3 (43 %) testes were classified as Cosentino 2, 3 (43%) as Cosentino 3 and 1 (14 %) as Cosentino 4. In the T/D +alprostadil group, 5 (50 %) testes were classified as Cosentino 2, 3 (30 %) as Cosentino 3 and 2 (20%) as Cosentino 4. CONCLUSION: The present study indicated that spermatic cord administration of alprostadil and papaverine showed a protective effect against ischemia/reperfusion injury after right-side testes torsion and histological changes were decreased after testicular ischemia reperfusion injury.

Parotid Mucoepidermoid Carcinoma Mimicking a Large Mucocele.

Mucoepidermoid carcinoma is a malign tumor involving the parotid gland and minor salivary glands. Parotid pure cystic mucoepidermoid carcinoma can also masquerade mucocele, and hence, histopathological examination is crucial to distinguish the 2. Herein, the authors report a patient of mucoepidermoid carcinoma presenting as an asymptomatic mucocele-like cystic parotid mass. A 69-year-old female presented with cystic parotid mass; her examination findings and diagnostic imaging were consistent with that of mucocele. Histological examination revealed mucoepidermoid carcinoma. This case indicates that parotid mucocele-like cysts should be included in the differential diagnosis of malign salivary gland tumors.

Abatacept as a therapeutic option in the treatment of encapsulated peritoneal sclerosis: an experimental rat model.

PURPOSE: Encapsulated peritoneal sclerosis (EPS) is a rare complication of long-term peritoneal dialysis (PD) and is usually associated with mortality. Inflammation is a leading factor for developing EPS. This study aimed to investigate the effect of abatacept on peritoneal fibrosis and inflammation using the EPS rat model. METHODS: Twenty-four Wistar albino rats were randomly divided into four equal groups. Group I (control group) was administered isotonic saline (IS) via the intraperitoneal (ip) route during weeks 0-3. Chlorhexidine gluconate (CG) ip was administered to group II (CG group) during weeks 0-3. Group III (CG + IS group) received CG for the first 21 days and IS solution for the following 3 weeks. Group IV (abatacept group) received CG during weeks 0-3, and subsequently, 50 mcg/day abatacept during weeks 4-6. Peritoneal thickness, fibrosis, and inflammation were examined using light microscopy. Expressions of matrix metalloproteinase-2 (MMP-2) and transforming growth factor-beta 1 (TGF-ß1) were detected by immunohistochemical staining. RESULTS: Lesser peritoneal thickness and lower inflammation score were observed in the abatacept group than in the CG and CG + IS groups (p < 0.05). Furthermore, the abatacept group had a lower fibrosis score than the CG + IS group (p < 0.05). MMP-2 and TGF-ß1 scores were lower in the abatacept group than in the CG + IS group (p < 0.05). CONCLUSIONS: The results revealed that abatacept had a histopathological beneficial effect on peritoneal fibrosis, inflammation, MMP-2, and TGF-ß1 scores, which were induced by CG. Abatacept could be a new therapeutic option for treating EPS.

Do Histopathological Features and Microcalcification Affect the Elasticity of Breast Cancer?

OBJECTIVES: The aim of this study was to evaluate any association between histological grade, molecular subtypes of breast cancer, and strain elastography, and to investigate whether microcalcification affects the stiffness of tumor in breast cancers with the same histological grade. METHODS: Between April 2015 and March 2016, 94 lesions of 94 patients with the diagnosis of invasive ductal carcinoma were included in the study. Strain elastography was performed on all patients before biopsy. Histological grades (Grades 1, 2, and 3), molecular subtypes (luminal A, luminal B, Her-2, and basal-like), and strain ratio (SR) were compared. In the same histological grades, patients were divided into two groups according to the presence of microcalcifications, and the groups were compared with each other. RESULTS: Compared with Grades 1 (20.5) and 2 (23.7), Grade 3 (11.7) showed lower SR values (Grade 3-2, P = .01; Grade 3-1, P = .2). The groups with microcalcification had slightly higher SR in all histological grades, but not of statistical significance. In molecular subtypes, luminal A and B demonstrated higher SR, whereas HER2 and basal-like had lower SR (P > .05 for all group comparisons). CONCLUSIONS: Grade 3 invasive ductal carcinomas are different from other grades with lower SR values. The presence of microcalcifications and molecular subtypes do not affect elasticity like a high histological grade does.

Evaluation of MUC1 and P53 expressions in noninvasive papillary urothelial neoplasms of bladder, their relationship with tumor grade and role in the differential diagnosis.

PURPOSE: The aim of this study was to investigate the usability of MUC1 and p53 for differential diagnosis of noninvasive papillary urothelial neoplasias, especially for distinguishing papillary urothelial neoplasm of low malignant potential (PUNLMP) from low-grade papillary urothelial carcinoma (LGPUC) when the histologic signs are not obvious. MATERIALS AND METHODS: Seventeen biopsy specimens of the patients with PUNLMP, 20 with LGPUC and 13 with high-grade papillary urothelial carcinoma (HGPUC) were stained for MUC1 and p53 protein by immunohistochemical methods. Histological grading was performed according to an algorithm, which allows histological parameters used in 2004 WHO/ISUP 1998. RESULTS: We had obvious statistical difference for aberrant expression pattern of MUC1 between PUNLMP and LGPUC-HGPUC (P = 0.007). Positivity of MUC1 expression in cytoplasm of basal cells was more observed in HGPUC and LGPUC, whereas PUNLMP was more often showing apical and superficial positivity of MUC1 expression (P = 0.001 and 0.011). Nuclear p53 protein in HGPUC was obviously more frequent than that in LGPUC and PUNLMP (P < 0.001). Measures showed statistical difference among aberrant MUC1 expression, p53 overexpression, and tumor grade (P < 0.001). CONCLUSIONS: MUC1 and p53 may be helpful immunohistochemical markers for distinguishing PUNLMP from LGPUC and HGPUC, when the histologic signs are not obvious.

Placental Elasticity and Histopathological Findings in Normal and Intra-Uterine Growth Restriction Pregnancies Assessed with Strain Elastography in Ex Vivo Placenta.

The aim of this study was to investigate the differences of placental elasticity between intra-uterine growth restriction (IUGR) and normal pregnancies to show whether or not there is any association between histopathological changes and placental elasticity. Fifty-five human placentas were collected at delivery, including 25 with IUGR and 30 controls. Strain elastography (SE) was performed ex vivo and all placentas were examined histopathologically. Elasticity index (EI) and histopathological findings were compared between groups. The placental stiffness and presence of histopathological changes were higher in the IUGR group than in controls (p < 0.05). Also, histopathological findings were associated with decreased EI values, but no specific patterns of histologic abnormalities were identified except villitis and delayed villous maturity. Distinct reduced placental elasticity could be the result of the cumulative effects of all the histologic findings in IUGR.

Conjunctival Cytological Alterations in Ocular Behçet Disease.

PURPOSE: To evaluate the ocular surface alterations and tear film functions in patients with ocular Behçet disease (BD). METHODS: This study included 48 eyes of 48 patients with inactive BD and a control group of 33 age- and sex-matched subjects. Schirmer I and tear break-up time (TBUT) tests were used to evaluate the tear film of the subjects. Impression cytology was used to evaluate morphological changes of the conjunctival surface epithelial cells. RESULTS: The mean Schirmer I test result was 11.6 ± 5.9 mm/5 minutes and 16.1 ± 4.6 mm/5 minutes in the Behçet and control groups, respectively. The mean TBUT test result was 9.8 ± 5.6 seconds and 13.2 ± 5.7 seconds in the study and control groups, respectively. The Schirmer and TBUT test results were significantly lower in the study group than in the controls (P = 0.001 and P = 0.011, respectively). The mean impression cytology score was 1.3 ± 0.9 in the study group and significantly higher than the control group value of 0.4 ± 0.6 (P = 0.001). CONCLUSIONS: Tear film functions and conjunctival surface epithelial morphology were significantly altered in patients with ocular BD.

A Novel Technique for Conjunctivoplasty in a Rabbit Model: Platelet-Rich Fibrin Membrane Grafting.

Purpose. To investigate the effect of platelet-rich fibrin (PRF) membrane on wound healing. Methods. Twenty-four right eyes of 24 New Zealand rabbits equally divided into 2 groups for the study design. After the creation of 5 × 5 mm conjunctival damage, it was secured with PRF membrane, which was generated from the rabbit's whole blood samples in PRF membrane group, whereas damage was left unsutured in the control group. Three animals were sacrificed in each group on the 1st, 3rd, 7th, and 28th postoperative days. Immunohistochemical (IHC) stainings and biomicroscopic evaluation were performed and compared between groups. Results. PRF membrane generated significant expressions of vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-ß), and platelet-derived growth factor (PDGF) in the early postoperative period. However, the IHC evaluation allowed showing the excessive staining at day 28, in control group. Biomicroscopic evaluation revealed complete epithelialization in PRF membrane group, but none of the cases showed complete healing in the control group. Conclusions. This experimental study showed us the beneficial effects of the PRF membrane on conjunctival healing. Besides its chemical effects, it provides mechanical support as a scaffold for the migrating cells that are important for ocular surface regeneration. These overall results encourage us to apply autologous PRF membrane as a growth factor-enriched endogenous scaffold for ocular surface reconstruction.

Effect of Enoxaparin Sodium on Experimentally-Induced Myringosclerosis in Rats.

OBJECTIVE: To evaluate the effectiveness of enoxaparin sodium (ES) on experimentally-induced myringosclerosis in rats. MATERIALS AND METHODS: Twenty Wistar albino-type rats weighing up to 250-300 g each were randomized into four groups containing five rats each and were then bilaterally myringotomized. The control group (n=5) received intratympanic serum physiologic injections, whereas ES2 (n=5), ES4 (n=5), and ES6 groups (n=5) received intratympanic ES of 2000 IU, 4000 IU, and 6000 IU, respectively, for 10 days after myringotomy. Rats were sacrificed at 60 days after intratympanic application and were then prepared for histopathologic evaluation. RESULTS: As for tympanic membrane hyaline degeneration, there were statistically significant differences among the control, ES2, ES4, and ES6 groups (p<0.05). As for fibrosis formation on tympanic membranes, a statistically significant difference was observed among the control and study groups; however, although not statistically significant, the formation of fibrosis was slowed down in the ES2 and ES4 groups compared with the control group. The control and study groups did not show any significant difference for calcification, hyperemia, and tympanic membrane thickening (p>0.05). CONCLUSION: Although our study and control groups comprised limited number of animals, and only one parameter demonstrated a statistically significant difference between the groups, ES may have an ameliorating effect on myringosclerosis induced by myringotomy in the tympanic membranes of rats. ES proved to be effective in the prevention of hyaline disc formation. Further studies should be conducted for better understanding of the effects of low-molecular-weight heparin (LMWH) (i.e., enoxaparin) on myringosclerosis.

The effect of intraurethral dexpanthenol on healing and fibrosis in rats with experimentally induced urethral trauma.

OBJECTIVE: To determine the efficacy of dexpanthenol applied early after urethral trauma for preventing inflammation and spongiofibrosis. MATERIALS AND METHODS: Twenty-seven rats were randomized and divided into 3 groups, with 9 rats in each group. The urethras of all rats were traumatized with a pediatric urethrotome knife at 6-o' clock. For 14 days, group I was given 0.9% saline twice a day (control group), group II was given dexpanthenol 500 mg/kg ampules once a day and 0.9% saline once a day, and group III was given dexpanthenol 500 mg/kg ampules twice a day intraurethrally using a 22 ga catheter sheath. On day 15, the penises of the rats were degloved to perform penectomy. RESULTS: The mean fibrosis scores were 2.4, 2.2, and 1.4, and mean inflammation scar scores were 2, 1.4, and 1.3 in groups I, II, and III, respectively. There was a significant difference between groups I and II for inflammation (P = .011); however, the difference for fibrosis was not significant (P = .331). The differences between groups I and III were statistically significantly different both for inflammation and fibrosis (P = .004 and P = .003, respectively). Groups II and III were not different significantly for inflammation (P = .638); however, there was less fibrosis in group III, in which high-dose dexpanthenol was administered. CONCLUSION: We showed that dexpanthenol applied early after urethral trauma significantly decreased inflammation and spongiofibrosis. We hope that our study will help to decrease strictures after urethral trauma and contribute to pharmaceutical investigations aiming to improve the success of the surgery for urethral strictures.

Evaluation of TRPM (transient receptor potential melastatin) genes expressions in myocardial ischemia and reperfusion.

In the present study, the expression levels of TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, and TRPM8 genes were evaluated in heart tissues after ischemia/reperfusion (IR). For this study, 30 albino male Wistar rats were equally divided into three groups as follows: Group 1: control group (n:10), Group II: ischemia group (ischemia for 60 min) (n:10) and Group III: IR (reperfusion 48 h after ischemia for 60 min and reperfusion for 48 h). The expression levels of the TRPM genes were analyzed by semi-quantitative reverse transcriptase-PCR. When compared to the ischemia control, the expression levels of TRPM2, TRPM4, and TRPM6 did not change, whereas that of TRPM7 increased. However, TRPM1, TRPM3, TRPM5, and TRPM8 were not expressed in heart tissue. Histopathological analysis of the myocardial tissues showed that the structures that were most damaged were those exposed to IR. The findings showed that there is a positive relationship between TRPM7 expression and myocardial IR injury.

Beneficial effects of Etanercept on experimental necrotizing enterocolitis.

PURPOSE: Tissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an uncontrolled inflammatory response. The aim of this study was to investigate any potential anti-inflammatory effects that Etanercept may have on the inflammatory response in an experimental NEC model in newborn rats. METHODS: Newborn pups were randomized into three groups immediately after birth (Control, NEC + Placebo and NEC + Etanercept). Pups in the NEC + Placebo and NEC + Etanercept groups were subjected to an NEC-inducing protocol (hypercarbia, hypothermia and hyperoxia) twice a day for 3 days. Pups in the NEC + Etanercept group were given an intraperitoneal injection of Etanercept. Rats were harvested for biochemical and histopathological examinations. RESULTS: The histopathological injury score of rats in the NEC + Placebo group was significantly higher compared to the NEC + Etanercept and Control groups (p < 0.05 for both comparisons). Tissue levels of tumor necrosis factor-α, interleukin-1ß, and malondialdehyde were higher in the placebo group compared to the Etanercept group. CONCLUSION: Our results suggest that Etanercept attenuates intestinal tissue damage in NEC by reducing inflammation and blocking the production of free-oxygen radicals, while also reducing tissue levels of tumor necrosis factor-α and interleukin-1ß.

Multiple sub-epidermal calcified nodule mimicking eruptive xanthoma: a case report and review of the literature.

Sub-epidermal calcified nodule (SCN) is an uncommon form of idiopathic calcinosis. It usually occurs in children, particularly in the head and neck region, presenting as a solitary, painless, yellow-white nodule with papillomatous features. These lesions occur twice as common in males compared with females. The pathogenesis is uncertain, but the clinical and histological features of this lesion are distinctive. We report a case of 22-year-old man with multiple nodules bilaterally located on the dorsum of hands simulating eruptive xanthoma. Histopathological examination of one of the excised lesion confirmed the diagnosis showing epidermal and sub-epidermal deposition of calcium. This paper presents a review of the literature and adds a new case of SCN.

Is colchicine therapy effective in all patients with secondary amyloidosis?

OBJECTIVE: Although colchicine is effective on prevention and regression of amyloidosis in many cases, rate of unresponsiveness to colchicine therapy is not too low. However, there is no sufficient data about which factors effect to response of colchicine therapy on regression of amyloidosis. MATERIALS AND METHODS: 24 patients with renal amyloidosis were enrolled into the study. The patients were divided in two groups according to urinary protein excretions: non-nephrotic stage (14/24) and nephrotic stage (10/24). The patients were also categorized according to the etiology of amyloidosis; familial Mediterranean fever (FMF)-associated amyloidosis (15/24) versus rheumatoid disorders (RD)-associated amyloidosis (9/24). The changes of amount of proteinuria and estimated glomerular filtration rates were investigated after colchicine treatment started in these groups. RESULTS: The mean follow-up period was 27.7 ± 19.2 months. After initiating colchicine therapy, the degree of proteinuria was decreased higher than 50% in 11/14 (78%) of non-nephrotic patients and elevated only in three (22%) patients. In nephrotic group, proteinuria was increased in 5/10 (50%) of patients. Glomerular filtration rates were stable in nephrotic and non-nephrotic groups. Presenting with nephrotic syndrome was higher in RD-associated amyloidosis (RD_A) group (5/9) than FMF-associated amyloidosis (FMF_A) group (5/15) without statistical significance (p > 0.05). After colchicine treatment, proteinuria was decreased in 12/15 patients in FMF_A group, however, the significant decreasing of proteinuria was not observed in RD_A group (p = 0.05 vs. p > 0.05). CONCLUSION: Colchicine therapy was found more effective in low proteinuric stage of amyloidosis. The beneficial effect of colchicine therapy was not observed in patients with RD- associated amyloidosis.

All-trans-retinoic acid attenuates intestinal injury in a neonatal rat model of necrotizing enterocolitis.

BACKGROUND: Ischemia/reperfusion-induced intestinal injury is mediated by reactive oxygen species and inflammatory mediators. OBJECTIVES: This study was designed to evaluate whether all-trans-retinoic acid (ATRA) administration can attenuate intestinal injury and to analyze the antioxidant and anti-inflammatory effects of ATRA in a neonatal rat model of necrotizing enterocolitis (NEC). METHODS: Twenty-nine Wistar albino rat pups were randomly divided into 3 groups: group 1 = control, group 2 = NEC and saline, and group 3 = NEC and ATRA treatment. NEC was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at +4°C and oxygen. Pups in group 3 were injected intraperitoneally with ATRA (0.5 mg/kg body weight) once a day prior to each NEC procedure, beginning on postnatal day 1 and daily through postnatal day 4. The pups were killed on the 4th day and their intestinal tissues were harvested for biochemical and histopathological analysis. RESULTS: Mucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than other groups (p < 0.05). Intestinal superoxide dismutase and glutathione peroxidase activities in group 3 were significantly higher than group 2 (p = 0.04 and p = 0.04, respectively). Intestinal tissue tumor necrosis factor-α levels were significantly reduced with ATRA treatment in group 3 compared to group 2 (p < 0.001). CONCLUSIONS: It is likely that oxidative stress and inflammatory mediators contributed to the pathogenesis of NEC and that ATRA had a protective effect on intestinal injury through its anti-inflammatory and antioxidant properties.