The relationship between mutation carriage of BRCA1/2 and clinicopathological characteristics in women with breast cancer - experience from a diagnostic centre in Turkey.

The 5-10% of breast cancers (BC) are hereditary, and BRCA1/2 are causative in 25% of those inherited. It was aimed to examine the BRCA1/2 genotype-BC phenotype relationship. In 170 female patients with BC, BRCA1/2 genes were investigated using Next Generation Sequencing. Demographic and clinicopathological characteristics of the patients and correlations of pedigree analysis with BRCA1/2 mutation status were analysed. BRCA1/2 carriage was found to be 9.4%. When the patients were grouped as ≤ 40 and > 40 according to the age at diagnosis of BC, the tumour grade was higher in the ≤ 40 groups. In the study, BRCA1/2 carriage and tumour grade were higher in patients with triple-negative breast cancers (TNBC). The risk of TNBC was 5.560 times higher in BRCA1/2 carriers than in non-carriers. There is a significant relationship between BRCA1/2 carrier and BC hormone receptor negativity, tumour grade, and BC diagnosis age.

A Case of Circumscribed Palmar or Plantar Hypokeratosis and a Mini-review of the Literature.

ABSTRACT: Circumscribed palmar or plantar hypokeratosis (CPPH) is a new dermatologic disorder that firstly defined Pérez A et al in 2002. Since that time, further cases of CPPH have been reported by different authors in different countries. We report a 69-year-old Turkish woman who presented with asymptomatic, erythematous patches on the thenar region of the left hand and on the second left finger. Skin biopsy showed histological features of CPPH. In this article, it was emphasized that CPPH may be seen more frequently than expected and the clinical and pathological features of this disease with suspected malignant transformation should be known.

Drug-Induced Histiocytoid Sweet Syndrome: Two Cases With Levofloxacin and Amoxicillin-Clavulanate.

ABSTRACT: Histiocytoid Sweet syndrome (HSS) is an uncommon histologic variant of Sweet syndrome (SS). HSS can be distinguished from the classic SS with an infiltrate of histiocyte-like immature myeloid cells rather than dense neutrophilic infiltration, although the clinical features are similar. Previous studies have shown that the risk of hematologic malignancy is significantly higher in HSS compared with classic SS. To lesser extent, HSS is also associated with infections, inflammatory diseases, and drugs, particularly with antineoplastic agents as well. Here, we report a case of 2 patients with an abrupt onset of erythematous, tender plaques accompanied by fever, with that revealed similar histopathologic and immunohistochemical features, whom had a history of antibiotic use. Clinicopathologic correlation led to diagnosis of drug-induced HSS, associated with the use of levofloxacin and amoxicillin-clavulanate, respectively. Both patients were then successfully treated with systemic corticosteroid therapy, and neither of them had recurrence during the period of 24-month follow-up.

Necl 4 and RNase 5 Are Important Biomarkers for Gastric and Colon Adenocarcinomas.

BACKGROUND There is a need to identify new prognostic factors that may be used in addition to the known risk factors in gastrointestinal adenocarcinomas. In this study, we aimed to determine the expression of Necl 4 and RNase 5 biomarkers in gastric and colon adenocarcinomas, as well as the prognostic efficacy of these biomarkers in gastric and colon adenocarcinomas. MATERIAL AND METHODS Ninety-two cases resected due to stomach and colon adenocarcinoma were included in the study. The expression of Necl 4 and RNase 5 biomarkers was evaluated by immunohistochemical staining of the stomach and colon normal mucosa and adenocarcinoma areas. RESULTS In colon adenocarcinomas, there was a significant association between Necl 4 and lymphovascular invasion, vascular invasion, and perineural invasion (p<0.05). There was a significant association between RNase 5 and histological differentiation in colon adenocarcinomas (p<0.05). There was no association between RNase 5 and Necl 4 in gastric or colon adenocarcinomas. CONCLUSIONS Necl 4 may have prognostic value in colon adenocarcinomas, but it is difficult to ascertain in gastric adenocarcinomas.

Lack of evidence of HPV etiology of prostate cancer following radical surgery and higher frequency of the Arg/Pro genotype in Turkish men with prostate cancer.

OBJECTIVES: The aim of this study was to assess the possible role of HPV in the development of prostate cancer (PCa) and investigate the distribution of the p53 codon 72 polymorphism in PCa in a Turkish population. MATERIALS AND METHODS: A total of 96 tissues, which had been obtained using a radical surgery method, formalin-fixed and parafin-embedded, were used in this study. The study group consisted of 60 PCa tissues (open radical prostatectomy) and the control group contained 36 benign prostatic hyperplasia tissues (BPH) (transvesical open prostatectomy). The presence of HPV and the p53 codon 72 polymorphism was investigated in both groups using real-time PCR and pyrosequencing. RESULTS: The results of the real-time PCR showed no HPV DNA in any of the 36 BPH tissue samples. HPV-DNA was positive in only 1 of the 60 PCa samples (1.7%). The HPV type of this sample was identified as HPV-57. The distribution of the three genotypes, Arg/Arg, Arg/Pro and Pro/Pro was found to be 45.6, 45.6, and 8.8% in the PCa group and 57.1%, 34.3% and 8.6% in the control group, respectively. Compared with the control group, patients with PCa had a higher frequency of the Arg/Pro genotype and Proline allele (odds ratio (OR)=1.67, 95% confidence interval (CI)=0.68-4.09, p=0.044; OR=1.13, 95% CI=0.76-1.68, p=0.021, respectively). CONCLUSIONS: The results of the study do not support the hyphothesis that prostate cancer is associated with HPV infection but indicated that Proline allele can be a risk factor in the development of PCa in the Turkish population.

Curcumin Attenuates Inflammation, Oxidative Stress, and Ultrastructural Damage Induced by Spinal Cord Ischemia-Reperfusion Injury in Rats.

OBJECTIVES: Curcumin is a molecule found in turmeric root that possesses anti-inflammatory and antioxidant properties and has been widely used to treat neurodegenerative diseases. We investigated whether curcumin stimulates the neurorepair process and improves locomotor function in a rat model of spinal cord ischemia-reperfusion injury. METHODS: Thirty-two Wistar albino rats (190-220 g) were randomly allocated into 4 groups of 8 rats each: 1 sham-operated group and 3 ischemia-reperfusion injury groups that received intraperitoneal injections of saline vehicle, methylprednisolone (MP, 30 mg/kg following induction of ischemia-reperfusion [IR] injury), or curcumin (200 mg/kg for 7 days before induction of IR injury). Spinal cord IR injury was induced by occlusion of the abdominal aorta for 30 minutes. After 24 hours of reperfusion, locomotor function was assessed using the Basso, Beattie, and Bresnahan scale. All animals were sacrificed. Spinal cord tissues were harvested to evaluate histopathological and ultrastructural alterations and to analyze levels of malondialdehyde, tumor necrosis factor-alpha, interleukin-1 beta, nitric oxide, and caspase-3, as well as enzyme activities of superoxide dismutase and glutathione peroxidase. RESULTS: Intraperitoneal administration of curcumin significantly reduced inflammatory cytokine expression, attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in comparison to treatment with MP or saline. Histopathological and ultrastructural abnormalities were significantly reduced in curcumin-treated rats compared to the MP- and saline-treated groups. Furthermore, curcumin significantly improved locomotor function. CONCLUSIONS: Curcumin treatment preserves neuronal viability against inflammation, oxidative stress, and apoptosis associated with ischemia-reperfusion injury.

An experimental comparison of the effects of propolis, curcumin, and methylprednisolone on crush injuries of the sciatic nerve.

BACKGROUND: Propolis and curcumin have antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective features. The goal of this study was to determine the effects of propolis and curcumin on nerve healing in rat sciatic nerve crush injuries and to compare these effects with results obtained using steroid treatment. METHODS: In the sham group, the right sciatic nerves of rats were dissected and exposed, and the skin was closed without any additional manipulation. In the control group (group C), after the right sciatic nerves of rats were exposed, crush damage was inflicted using a surgical clamp. In the control-methylprednisolone group, crush injuries were inflicted on sciatic nerves as in group C. After injury, 1-mg/kg methylprednisolone was administered daily for 6 days and was then tapered for 4 days. In the curcumin group, crush injuries were inflicted on sciatic nerves as in group C. Then, 100-mg/kg curcumin was given every day. In the propolis group, crush injuries were inflicted on sciatic nerves as in group C. Then, 200-mg/kg propolis was given every day. Rats were evaluated after 28 days using functional (walking track analysis and electrophysiological measurements), histomorphometric, electron microscopic, and muscle weight measurements. RESULTS: Compared to the control groups, the curcumin and propolis groups had better functional (walking track analysis and electrophysiological) results after experimental peripheral nerve crush injury. CONCLUSIONS: Curcumin and propolis, 2 traditional drugs, had a positive effect on nerve crush injuries. We are convinced that they can be used to support routine treatment in such nerve injuries.

Relationship among mismatch repair deficiency, CDX2 loss, p53 and E-cadherin in colon carcinoma and suitability of using a double panel of mismatch repair proteins by immunohistochemistry.

Biomarkers such as mismatch repair proteins, CDX2, p53, and E-cadherin are blamed for colon cancers, but the relationships of these biomarkers with each other and with pathological risk factors in colon carcinoma are still not clear. The aim of this study was to evaluate the association of these biomarkers with each other by using immunohistochemical staining and to compare their expression with pathological risk factors for colonic adenocarcinoma. We also aimed to study the usability of a double panel of mismatch repair proteins. One hundred and eleven cases with colonic adenocarcinoma were examined. There was a statistically significant relationship between tumor histological differentiation and perineural invasion, vascular invasion, mismatch repair deficiency, p53, CDX2, and E-cadherin (p < 0.05). PMS2 and MSH6 loss covered 100% of cases with mismatch repair deficiency. Mismatch repair deficiency was correlated with CDX2 loss and E-cadherin expression (p < 0.05). It was also observed that cases with PMS2 loss covered all the cases with CDX2 loss. In conclusion, this double panel may be used instead of a quadruple panel for detecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together.

Borax partially prevents neurologic disability and oxidative stress in experimental spinal cord ischemia/reperfusion injury.

OBJECTIVES: The aim of this study is to investigate the potential effects of borax on ischemia/reperfusion injury of the rat spinal cord. METHODS: Twenty-one Wistar albino rats were divided into 3 groups: sham (no ischemia/reperfusion), ischemia/reperfusion, and borax (ischemia/reperfusion + borax); each group was consist of 7 animals. Infrarenal aortic cross clamp was applied for 30 minutes to generate spinal cord ischemia. Animals were evaluated functionally with the Basso, Beattie, and Bresnahan scoring system and inclined-plane test. The spinal cord tissue samples were harvested to analyze tissue concentrations of nitric oxide, nitric oxide synthase activity, xanthine oxidase activity, total antioxidant capacity, and total oxidant status and to perform histopathological examination. RESULTS: At the 72nd hour after ischemia, the borax group had significantly higher Basso, Beattie, and Bresnahan and inclined-plane scores than those of ischemia/reperfusion group. Histopathological examination of spinal cord tissues in borax group showed that treatment with borax significantly reduced the degree of spinal cord edema, inflammation, and tissue injury disclosed by light microscopy. Xanthine oxidase activity and total oxidant status levels of the ischemia/reperfusion group were significantly higher than those of the sham and borax groups (P < .05), and total antioxidant capacity levels of borax group were significantly higher than those of the ischemia/reperfusion group (P < .05). There was not a significantly difference between the sham and borax groups in terms of total antioxidant capacity levels (P > .05). The nitric oxide levels and nitric oxide synthase activity of all groups were similar (P > .05). CONCLUSIONS: Borax treatment seems to protect the spinal cord against injury in a rat ischemia/reperfusion model and improve neurological outcome.

The diagnostic importance of matrix metalloproteinase-7 and nestin in gastrointestinal stromal tumors.

BACKGROUND: The importance of the matrix metalloproteinase-7 (MMP-7) and nestin immunomarkers, C-kit proto-oncogene (CD117), and the efficiency of the Ki-67 proliferation index for gastrointestinal stromal tumors were evaluated. MATERIAL AND METHODS: This study was conducted by examining the microscope slides of 72 patients with gastrointestinal stromal tumors that were sent to the pathology laboratory between 2007 and 2012. Immunohistochemical staining for CD117, MMP-7, nestin, and marker of proliferation Ki-67 was performed. The correlations between the positive results for Ki-67, CD117, MMP-7, and nestin were evaluated relative to the tumor characteristics of size, localization, grade, cellular type, cellularity, cytology type, growth pattern, ulceration, necrosis, hemorrhage, invasion depth, and lymph node metastasis. RESULTS: The tumor was localized in the stomach in 42 of the patients, the intestines in 19, the colon in 7, and the rectum in 4. Comparisons among the groups showed that MMP-7 was correlated with the tumor grade (p<0.001), cellularity (p<0.009), cytologic atypia (p<0.001), ulceration (p=0.002), necrosis (p<0.001), and tumor size (p=0.001). Nestin was correlated with the tumor grade (p=0.013), and tumor size (p=0.024). Correlations among CD117, MMP-7, nestin, and Ki-67 were examined. Nestin and Ki-67 were both significantly correlated with CD117 and MMP-7 [(r=0.279, p=0.018), (r=0.322, p=0.006), (r=0.386, p=0.001), (r=0.386, p=0.002)], respectively. CONCLUSIONS: MMP-7 and nestin may be beneficial as markers, given their sensitivity to gastrointestinal stromal tumors.

Might Necrotic Keratinocytes Contribute to the Diagnosis and Pathogenesis of Psoriasis?

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease that can pose challenges for histopathological diagnosis. Recent research has emphasized the importance of necrotic keratinocytes, meaning keratinocytes undergoing programmed cell death, for diagnosing psoriasis. It has also become increasingly evident that programmed cell death pathways play a significant role in psoriasis's pathogenesis, development, and progression, including via a recently identified programmed cell death mechanism called "PANoptosis." OBJECTIVES: In our study, we aimed to investigate the significance of necrotic keratinocytes in both the diagnosis and pathogenesis of psoriasis. METHODS: We analyzed the number of necrotic keratinocytes in 135 samples of psoriasis, 57 samples of psoriasiform spongiotic dermatitis, and 71 samples of normal skin. We additionally assessed the distribution of necrotic keratinocytes in the upper, middle, and lower thirds of the epidermis. RESULTS: Our findings revealed a significant difference in the total number of necrotic keratinocytes and their distribution within epidermal regions between patients with psoriasis and both the psoriasiform spongiotic dermatitis and control groups (p < .001). In particular, necrotic keratinocytes were predominantly found in the upper epidermis (77.5%) in patients with psoriasis. We also observed a strong correlation between Psoriasis Area and Severity Index scores and the total count of necrotic keratinocytes in patients with psoriasis (r = .72). CONCLUSIONS: Our results highlight the role of necrotic keratinocytes, resulting from programmed cell death, as important marker cells in both the diagnosis and pathogenesis of psoriasis.

Isolated Elastofibroma of the Thigh: A Case Report.

A 55-year-old female presented with elastofibroma of the thigh. On presentation, she complained of a palpable, painful mass on the anterolateral right thigh that had been present for one year. She had a history of surgery for a right femur fracture. On MRI, a soft-tissue mass was seen in the vastus intermedius muscle, as a heterogeneous lesion with streaky fatty and fibrous components. The fibrous component was isointense to the muscle, and the fatty component had a high signal on both T1- and T2-weighted images. Histopathological analysis after biopsy established the diagnosis of elastofibroma.

Role of Adamts-1 in Pleomorphic Xanthoastrocytoma Tumor Cells Progression.

AIM: To analyze the expression of ADAMTS-1, NF-?B, and STAT3 in human pleomorphic xanthoastrocytoma specimens, and their correlation with glioma advancement. MATERIAL AND METHODS: Pleomorphic xanthoastrocytoma tumor cell lines were treated with low and high doses of cytokines at 24 and 48 hours (h) to replicate the inflammatory environment. The effects of IL-1 were assessed with the scratch wound-healing assay, and the expression levels of ADAMTS-1, NF-?B, and STAT3 of the groups were determined by western blot analysis. RESULTS: Cytokine treatment significantly increased the migration of PXA glioma cells after scratching at 24h and 48h time points. Similarly, 10 and 30 ng/mL IL-1 induced 1.86 and 1.94 fold increases, respectively, in ADAMTS-1 expression after 24h, and 3 and 3.27 fold increases, respectively, after 48h, compared with the non-treatment control group.10 and 30 ng/mL IL-1 doses caused 2.5 and 2.6 fold increase, in NF-?B protein levels after 24h, and 3.16 and 3.41 fold increases after 48h, compared with the non-treatment group. The protein levels of STAT3 after 24h were 2.62 and 2.43 fold higher, and 3.78 and 3.84 fold higher after 48 hours, with 10 and 30 ng/mL IL-1, compared with the non-treatment group. CONCLUSION: The proliferation and progression of glioma cells were proportional to the increased expression levels of ADAMTS-1, NF-?B, and STAT3. Our findings indicate that the proteolytic function of ADAMTS-1 may be associated with the malignant transformation of low-grade gliomas.

Effects of Ganoderma lucidum Polysaccharides on Different Pathways Involved in the Development of Spinal Cord Ischemia Reperfusion Injury: Biochemical, Histopathologic, and Ultrastructural Analysis in a Rat Model.

OBJECTIVE: Inflammation and oxidative stress are 2 important factors in the emergence of paraplegia associated with spinal cord ischemia-reperfusion injury (SCIRI) after thoracoabdominal aortic surgery. Here it is aimed to investigate the effects of Ganoderma lucidum polysaccharide (GLPS) on SCIRI. METHODS: Rats were randomly selected into 4 groups of 8 animals each: sham, ischemia, methylprednisolone, and GLPS. To research the impacts of various pathways that are efficacious in formation of SCIRI, tumor necrosis factor α, interleukin 1ß, nitric oxide, superoxide dismutase levels, and catalase, glutathione peroxidase activities, malondialdehyde levels, and caspase-3 activity were measured in tissues taken from the spinal cord of rats in all groups killed 24 hours after ischemia reperfusion injury. The Basso, Beattie, and Bresnahan locomotor scale and inclined plane test were used for neurologic assessment before and after SCIRI. In addition, histologic and ultrastructural analyses of tissue samples in all groups were performed. RESULTS: SCIRI also caused marked increase in tissue tumor necrosis factor α, interleukin 1ß, nitric oxide, malondialdehyde levels, and caspase-3 activity, because of inflammation, increased free radical generation, lipid peroxidation, and apoptosis, respectively. On the other hand, SCIRI caused significant reduction in tissue superoxide dismutase, glutathione peroxidase, and catalase activities. Pretreatment with GLPS likewise diminished the level of the spinal cord edema, inflammation, and tissue injury shown by pathologic and ultrastructural examination. Pretreatment with GLPS reversed all these biochemical changes and improved the altered neurologic status. CONCLUSIONS: These outcomes propose that pretreatment with GLPS prevents progression of SCIRI by alleviating inflammation, oxidation, and apoptosis.

Biochemical, pathological and ultrastructural investigation of whether lamotrigine has neuroprotective efficacy against spinal cord ischemia reperfusion injury.

INTRODUCTION: Lamotrigine, an anticonvulsant drug with inhibition properties of multi-ion channels, has been shown to be able to attenuates secondary neuronal damage by influencing different pathways. The aim of this study was to look into whether lamotrigine treatment could protect the spinal cord from experimental spinal cord ischemia-reperfusion injury. MATERIALS AND METHODS: Thirty-two rats, eight rats per group, were randomly assigned to the sham group in which only laparotomy was performed, and to the ischemia, methylprednisolone and lamotrigine groups, where the infrarenal aorta was clamped for thirty minutes to induce spinal cord ischemia-reperfusion injury. Tissue samples belonging to spinal cords were harvested from sacrificed animals twenty-four hours after reperfusion. Tumor necrosis factor-alpha levels, interleukin-1 beta levels, nitric oxide levels, superoxide dismutase activity, catalase activity, glutathione peroxidase activity, malondialdehyde levels and caspase-3 activity were studied. Light and electron microscopic evaluations were also performed to reveal the pathological alterations. Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test was used to evaluate neurofunctional status at the beginning of the study and just before the animals were sacrificed. RESULTS: Lamotrigine treatment provided significant improvement in the neurofunctional status by preventing the increase in cytokine expression, increased lipid peroxidation and oxidative stress, depletion of antioxidant enzymes activity and increased apoptosis, all of which contributing to spinal cord damage through different paths after ischemia reperfusion injury. Furthermore, lamotrigine treatment has shown improved results concerning the histopathological and ultrastructural scores and the functional tests. CONCLUSION: These results proposed that lamotrigine may be a useful therapeutic agent to prevent the neuronal damage developing after spinal cord ischemia-reperfusion injury.

Acetabular Surgery in the Prone Position Resulting in a Life-Threatening Splenic Injury: A Case Report.

CASE: The case reported involves a patient who developed an unexplained decrease in hemoglobin after acetabular fracture surgery in the prone position. Repeat abdominal computed tomography was remarkable for a massive subcapsular spleen hematoma secondary to rib fracture impingement, which required splenectomy. CONCLUSION: The spleen can be injured by a fracture rib during prone positioning for fixation of an acetabular fracture. Prone surgical positioning may cause iatrogenic intra-abdominal organ injury in patients with displaced lower rib fractures. Lateral positioning should be considered for acetabular surgery in patients with rib fractures.