Eleni Mylona

Pyogenic Vertebral Osteomyelitis: A Systematic Review of Clinical Characteristics

OBJECTIVES Vertebral osteomyelitis is a cause of back pain that can lead to neurologic deficits if not diagnosed in time and effectively treated. The objective of this study was to systematically review the clinical characteristics of pyogenic vertebral osteomyelitis (PVO). METHODS The authors conducted a systematic review of the English literature. The inclusion criteria included studies with 10 or more subjects diagnosed with PVO based on the combination of clinical presentation with either a definitive bacteriologic diagnosis or pathological and/or imaging studies. RESULTS The 14 studies that met selection criteria included 1008 patients with PVO. Of them, the majority (62%) were men, with back pain and fever as the most common presenting symptoms. Diabetes mellitus was the most common underlying medical illness, while the urinary tract was the commonest source of infection. Staphylococcus aureus was the most commonly isolated organism. Computed tomographic guided or open biopsy yielded the causative organism more often than blood cultures (77% versus 58%). Plain radiography showed abnormalities in 89% of the cases, while bone scanning and computed tomography or magnetic resonance imaging were positive in 94% of the cases, revealing lumbar as the most commonly affected area. The attributable mortality was 6%, while relapses and neurological deficits were described in the 32% and 32% of the cases, respectively. CONCLUSION PVO is an illness of middle-aged individuals with underlying medical illnesses. Although the mortality rate is low, relapses and neurological deficits are common, making early diagnosis a major challenge for the physician.

Study of phospho- β -catenin subcellular distribution in invasive breast carcinomas in relation to their phenotype and the clinical outcome

β-Catenin has a crucial role in cell–cell adhesion as well as a signaling role as a member of the Wnt pathway. The aim of this study was to examine the clinicopathological and prognostic value of phosphorylated β-catenin, as well as its relation to the tumors’ phenotype, in breast cancer. Immunohistochemistry was applied on 141 paraffin-embedded breast tissue specimens for the detection of phospho-β-catenin, ER, PR, c-erbB-2, p53, Ki-67, bcl-2, uPAR and TIMP-1. For each case, a phospho-β-catenin index was determined by image analysis. Phospho-β-catenin staining was detected in the cytoplasm and the nucleus of the malignant cells. Cytoplasmic phospho-β-catenin was statistically higher in carcinomas of smaller tumor size (P=0.030), lower stage (P=0.026), decreased Ki-67 and high c-erbB-2 immunoreactivity (P=0.052 and P=0.037, respectively). Nuclear phospho-β-catenin showed a parallel correlation with ER and ERβ (P=0.022 and P=0.043, respectively), bcl-2 (P=0.042), uPAR in cancer cells (P=0.041) and TIMP-1, although the correlation was borderline (P=0.066). Cytoplasmic phospho-β-catenin was found to be independently correlated with prolonged disease-free and overall survival (P=0.046 and P=0.002, respectively), whereas nuclear localization was correlated with a shortened overall survival (P=0.046). In conclusion, phospho-β-catenin may have a different involvement in invasive breast carcinomas, according to its subcellular distribution. Nuclear localization seems to be related to an aggressive tumor phenotype, negatively affecting patients’ overall survival, whereas cytoplasmic localization is associated with a favorable tumor phenotype and a longer disease-free and overall survival.

The clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 according to their localization in invasive breast carcinoma.

Aims:  To investigate the clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1‐MMP) and MMP‐9 proteins expression in invasive breast carcinoma and their relationship to tumour proliferation and expression of c‐erbB2 and peroxisome proliferator‐activated receptor (PPAR) gamma.

Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in invasive breast carcinoma: Relation to tumor phenotype and clinical outcome

IntroductionOur aim was to study the expression pattern of tissue inhibitor of metalloproteinases (TIMP)-3 protein in invasive breast carcinoma, and its clinicopathological and prognostic value as well as its relation to markers indicative of the tumor phenotype.MethodsImmunohistochemistry was performed on paraffin-embedded tissue specimens from 173 invasive breast carcinomas to detect the proteins TIMP-3, estrogen receptor (ER), progesterone receptor, p53, c-erbB-2, topoisomerase IIα and Bcl-2.ResultsTIMP-3 protein was immunodetected in the cytoplasm of the malignant cells and the peritumoral stroma, as well as in in situ carcinoma and normal epithelium. Reduced expression of TIMP-3 protein within cancer cells was correlated with carcinomas of high nuclear and histological grade (p = 0.032 and p = 0.015, respectively), and low ER expression (p = 0.053). Moreover, TIMP-3 immunopositivity was inversely correlated with the expression of p53 and topoIIα proteins (p = 0.002 and p = 0.008, respectively), whereas it was positively associated with Bcl-2 expression (p = 0.020). Reduced expression of TIMP-3 protein within cancer cells was found to have an unfavorable impact on disease-free survival (p = 0.052) in the entirety of the patient population, as well as in both subgroups of lymph-node-positive and mutant-p53-negative patients (p = 0.007 and p = 0.037, respectively). Stromal localization of TIMP-3 protein was found to have no clinicopathological or prognostic value.ConclusionThis is the first immunohistochemical study to show that TIMP-3 protein within cancer cells is associated with tumor phenotype. Reduced expression of TIMP-3 protein within cancer cells was found to correlate with an aggressive tumor phenotype, negatively affecting the disease-free survival of both subgroups of lymph node-positive and mutant-p53-negative patients.

Immunohistochemical study of PTEN and phosphorylated mTOR proteins in familial and sporadic invasive breast carcinomas

Bakarakos P, Theohari I, Nomikos A, Mylona E, Papadimitriou C, Dimopoulos A‐M & Nakopoulou L
(2010) Histopathology 56, 876–882
Immunohistochemical study of PTEN and phosphorylated mTOR proteins in familial and sporadic invasive breast carcinomas

Acute hepatitis in adult Still’s disease during corticosteroid treatment successfully treated with anakinra

Adult onset Still’s disease (AOSD) is a well-recognized clinical disorder characterized by involvement of various organs, including liver. However, acute hepatitis or hepatic failure is extremely rare, and most of the reported cases occurred during treatment with hepatotoxic drugs. Anakinra is an interleukin-1 receptor antagonist (IL-1Ra). Experimental and clinical data support a central role for IL-1Ra in fulminant hepatic failure. We report the case of a patient with AOSD complicated with acute hepatitis during treatment with corticosteroids, which was dramatically improved with anakinra.

Gastric Syphilis: a systematic review of published cases of the last 50 years.

The authors conducted a systematic review of the English literature for cases of Gastric Syphilis (GS) in the last 50 years. The 34 studies which met selection criteria included 52 patients with GS. Of the reviewed patients, only 13% had a history of syphilis diagnosis and 46% had prior or concurrent clinical manifestations of the disease. Epigastric pain/fullness was the most common presenting symptom (92%) and epigastric tenderness being the most common sign. Gastric bleeding of variable intensity was documented in 35% of the cases. In the radiologic examinations, fibrotic narrowing and rigidity of the gastric wall was the most common finding (43%), followed by hypertrophic and irregular folds, while in endoscopy the most common lesion types were multiple ulcerations (48%), nodular mucosa, and erosions. The antrum was the most commonly affected area (56%). The majority of the patients received penicillin (83%) with a rapid resolution of their symptoms. Seventeen percent of the patients were treated surgically either due to a complication or due to strong suspicion of infiltrating tumor or lymphoma. The nonspecific clinical, radiologic, and pathologic characteristics of GS can establish it as a great imitator of other gastric diseases. GS should be considered in the differential diagnosis in patients at risk for sexually transmitted diseases who present with abdominal complaints and unusual endoscopic lesions and no other diagnosis is made, irrespective of the presence of H. pylori. The absence of primary or secondary luetic lesions should not deter one from considering GS.

Effect of BRCA1 immunohistochemical localizations on prognosis of patients with sporadic breast carcinomas.

Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin embedded tissue specimens from 111 sporadic, invasive breast carcinomas to detect the expression of the proteins BRCA1, ER, PR, erbB2, p53 and Ki67. BRCA1 protein was detected in the nuclei and the cytoplasm of the tumor cells. Nuclear BRCA1 immunoreactivity showed no relation with the classic clinicopathological markers and the expression of cerbB2, p53 and Ki67. Reduced expression of nuclear BRCA1 protein was found to exert an independent favorable impact on both the overall and relapse-free (RF) survival of the patients (p=0.019 and p=0.043, respectively). Cytoplasmic BRCA1 was associated with none of the classic histomorphological indices, except from the lymph node metastasis, with which its relation was found to be inverse (p=0.05), prolonging the RF survival of the patients (p=0.05). Our findings suggest that BRCA1 protein depicts different prognostic significance, according to its subcellular distribution. Nuclear detection of the protein was associated with a worse prognosis, while the cytoplasmic one was related to fewer recurrences as a result of fewer lymph node metastases.

Prognostic value of microsatellite instability determined by immunohistochemical staining of hMSH2 and hMSH6 in urothelial carcinoma of the bladder

Mismatch repair (MMR) genes are involved in the recognition and repair of acquired DNA damage, which arises during cell division, thus playing an essential role in preserving genetic stability. Immunohistochemistry was applied to 130 specimens from urothelial carcinoma (UC) of the bladder to detect expression of MMR gene products hMSH2 and hMSH6, and to investigate its clinicopathological and prognostic value. hMSH2 and hMSH6 protein expression was exclusively detected in the nuclei of malignant cells. Of the 112 cases evaluable for hMSH2, 29 (25.9%) were negative and of the 130 UCs evaluable for hMSH6, 64 (49.2%) were negative, and were thus considered to depict MSI. Nuclear hMSH2 values were statistically lower in non‐invasive UCs (Ta‐T1) (p=0.013) and in carcinomas with decreased p53 staining (p=0.04). Lower hMSH6 values were more often met in well‐differentiated tumors (p<0.0001) and in tumors with low expression of p53 (p=0.016), topoIIα and caspase 3 (p=0.017 and p=0.018, respectively). Both hMSH2‐ and hMSH6‐negative immunoreactions were found to have a favorable impact on overall patient survival (p=0.041 and p=0.034, respectively), this finding being further verified in the multivariate analysis of hMSH2 (p=0.026). This is the first study to show that lack (and not reduction designated according to various cut‐off points) of hMSH2 and hMSH6 correlated with non‐invasive tumors of lower grade and is of favorable prognostic significance in patients suffering from bladder carcinoma.

Cyclin D1 in invasive breast carcinoma: favourable prognostic significance in unselected patients and within subgroups with an aggressive phenotype.

Aims:  To study the clinicopathological and prognostic value of cyclin D1 overexpression in patients with breast carcinoma.