Activated Akt expression in breast cancer: correlation with p53, Hdm2 and patient outcome.

Activation of protein kinase-B/Akt (pAkt) is mediated by oestrogen and involves HER-2 in vitro, to phosphorylate Hdm2 and influence p53 cytoplasmic localisation and degradation. Expression of all active Akt isoforms (pAkt) were examined, together with p53/Hdm2 subcellular expression in invasive ductal breast cancers (IDCs), to evaluate whether in vitro findings were related to clinical data and determine the effect on outcome. Immunohistochemical expression of serine 473 specific phosphorylated Akt (pAkt) isoforms (Akt-1,2,3) was evaluated in 97 patients, together with subcellular expression of p53/Hdm2. The results show that pAkt was evaluable in 95 patients with cytoplasmic expression in 81% and more likely to be associated with larger tumours (P=0.007), with no correlation with HER-2 expression. pAkt correlated with increasing levels of cytoplasmic p53 (P=0.025) and was associated with a reduced disease-free survival (P=0.04; univariate). In conclusion, pAkt has implications in breast cancer growth through mechanisms inactivating p53 with an association with immunohistochemical p53 expression, which is preferentially cytoplasmic. Despite in vitro associations, pAkt appears to be a variable marker of HER-2 expression.

Imprint cytology from ultrasound-guided core biopsies: accurate and immediate diagnosis in a one-stop breast clinic.

AIM: To investigate whether imprint cytology from ultrasound-guided core biopsy specimens was adequate for the National Health Service Breast Screening Programme (NHSBSP) guidelines. METHODS: We prospectively audited imprint cytology from ultrasound-guided core biopsy specimens. The performance indicators for imprint cytology specimens from 111 consecutive ultrasound-guided core biopsy were compared with standards set by the NHSBSP for fine-needle aspiration cytology (FNAC). RESULTS: Imprint cytology fulfilled the "preferred" targets for absolute and complete sensitivity, specificity, positive predictive value, false-positive and false-negative rates, inadequate rate and inadequate rate from cancers. It also satisfied the minimum target for suspicious rate. The complete sensitivity was 97%, full specificity 78%, with 100% positive predictive value for C5 cytology and an inadequate rate from cancers of 1.5%. CONCLUSION: Imprint cytology from ultrasound-guided core biopsy allows same-day diagnosis and the collection of data regarding the grade of the carcinoma for treatment decisions from a single needle test.

p14ARF expression in invasive breast cancers and ductal carcinoma in situ--relationships to p53 and Hdm2.

INTRODUCTION: p14ARF stabilises nuclear p53, with a variable expression of p14ARF mRNA in breast cancers. In vitro, nuclear p14ARF binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. p14ARF is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of p14ARF protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic p14ARF, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the p14ARF/Hdm2 pathway to inactivate p14ARF and to influence Hdm2 activity and localisation. This study examined p14ARF and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome. METHODS: The 4C6 anti-p14ARF monoclonal antibody and Dako Envision Plus system were used to evaluate p14ARF expression in 103 patients; p53/Hdm2 staining was performed. RESULTS: p14ARF was evaluable in 96 patients, with nuclear p14ARF expression (modified Quick-score > or = 3) in 79% (n = 76) of IDCs and in associated DCIS in 74 patients. Cytoplasmic p14ARF was detectable in 23 breast cancers. Nuclear and cytoplasmic p14ARF showed no correlation with p53 subcellular immunoreactivity. Increasing levels of cytoplasmic p14ARF were associated with nuclear and cytoplasmic Hdm2 expression (P < 0.001). Subcellular ARF expression was not associated with clinicopathological parameters, and although not an independent prognosticator, these preliminary findings suggest that cytoplasmic p14ARF might be associated with a better overall survival (P = 0.09; log rank). The association between HER-2 positivity and nuclear p14ARF (P = 0.038), as well as nuclear Hdm2 (P = 0.019), reflects the in vitro findings of HER-2 interaction with the ARF/Hdm2 pathway. Cytoplasmic p53 and Hdm2 expression might have biological implications, through an association of cytoplasmic p53 with increased tumour proliferation (P = 0.005), and an improved overall survival (P = 0.002, log rank) in cytoplasmic Hdm2-expressing tumours, that independently predict favourable overall survival (P = 0.02) and disease-free survival (P = 0.03). CONCLUSIONS: Nuclear p14ARF expression is similar in IDCs and DCIS and is associated with Hdm2 immunoreactivity. Nuclear p14ARF and Hdm2 might be regulated by HER-2. Clearly, our findings in vivo suggest a complexity of p14ARF/Hdm2 and p53 pathways in which consideration of cytoplasmic p14ARF and Hdm2 might have tumorigenic implications.

Imprint cytology of parathyroid tissue in relation to other tissues of the neck and mediastinum.

OBJECTIVE: To retest the hypothesis that imprint cytology may be used to reliably diagnose parathyroid tissue and, if so, to ascertain whether accuracy in this technique may be easily attained. STUDY DESIGN: Imprint preparations from 15 parathyroid, 10 thyroid, 8 lymphoreticular and 2 adipose tissue specimens were assessed blindly by two pathologists, one of whom (pathologist B) had only limited experience with endocrine tissue imprint cytology. RESULTS: Both assessors consistently distinguished parathyroid and thyroid preparations from lymphoreticular and adipose tissue preparations. While there was occasional difficulty in distinguishing between parathyroid and thyroid preparations, this was usually attributable to the scanty nature of the preparations. No single cytologic feature allowed a distinction between parathyroid and thyroid tissue. However, by considering several relatively diagnostic features collectively, pathologist B showed an increase in specificity and sensitivity rates for distinguishing parathyroid from thyroid imprints from 82% to 100% and 57% to 83%, respectively. CONCLUSION: The high accuracy rates and rapid [table: see text] learning curve shown by imprint cytology in distinguishing between different neck or mediastinal tissue types, together with its time- and cost-cutting potential, support a role for the technique in the intraoperative diagnosis of parathyroid tissue.

Immature ovarian teratoma with mature peritoneal metastatic deposits showing glial, epithelial, and endometrioid differentiation: a case report and review of the literature.

A patient with multiple peritoneal metastases showing mature (grade 0) glial, epithelial, and endometriotic differentiation occurring 20 years after removal of a grade 1 immature ovarian teratoma is reported. Although previous cases of endometriosis occurring in association with gliomatosis peritonei and a case of epithelial differentiation in metastases from an immature ovarian teratoma have previously been reported, this case would appear to be unique. Attention is drawn to similar, well-differentiated, metastases occurring in testicular teratomas.

Xanthogranulomatous pyelonephritis in childhood: pre-operative diagnosis is possible.

OBJECTIVE: To diagnose xanthogranulomatous pyelonephritis (XGP) in childhood pre-operatively. PATIENTS AND METHODS: Eleven cases of XGP presenting to Birmingham Children's Hospital over a 10-year-period are reported. Nine (82%) were diagnosed preoperatively on the clinical and radiological findings. RESULTS: The characteristic clinical findings were urinary tract infection (9 cases), palpable renal mass (8 cases) and anaemia (8 cases). The most common radiological findings were enlarged kidney (9 cases), renal calculi (7 cases) and non-functioning kidney (6 cases). Renal ultrasound typically demonstrated a central echoic area (6 cases) and multiple hypoechoic areas in the parenchyma (7 cases). A computed tomography (CT) scan was performed in three cases. This showed characteristic multiple, low attenuation, unenhanced areas within the parenchyma with extension of the inflammatory process into peri-nephric fat (two cases). Ten cases (91%) were of the diffuse type. There was extension into the peri-nephric fat in eight cases (73%). Three cases (27%) were associated with congenital urological abnormalities. Nephrectomy was performed in 10 cases and a partial nephrectomy in one. CONCLUSION: XGP is uncommon in childhood but should always be considered in the differential diagnosis of renal masses, especially in the presence of anaemia. Nephrectomy usually results in a permanent cure.

Crohn's disease with pulmonary involvement in a 3 year old boy.

Extra-intestinal or metastatic Crohn's disease is being recognised increasingly, most commonly in the skin and genitourinary system. Only very rarely has it been reported in the lung. A 3 year old boy who presented with swollen gums and a persistent abnormality on his chest x ray is reported. Lung biopsy specimens showed multiple non-caseating epithelioid granulomas. Subsequent investigation showed the presence of intestinal Crohn's disease. The evidence for abnormal lung function in Crohn's disease and the possible pathogenesis of metastatic pulmonary Crohn's disease are discussed.

Measurement techniques for melanoma: a statistical comparison.

Inter- and intra-observer variation in measuring the depth of invasion of malignant melanomas was assessed using three different techniques: eye-piece graticule, stage Vernier, and projection image analysis. Significant variation was found for all methods but was least pronounced with the stage Vernier. It is recommended that this should be the preferred technique for routine use.

Fatal wheelchair-related accidents in the United States.

Of the 3.3 of every 1000 persons in the United States who use a wheelchair, an estimated 3.3% per year have a serious wheelchair-related accident. Yet, only isolated case reports of fatal accidents have appeared. To obtain a better estimate of the incidence and nature of fatal accidents, a search was carried out of the death certificate database (1973-1987) of the National Information Clearinghouse of the Consumer Product Safety Commission; 770 wheelchair-related deaths were identified. The majority, 596 persons (77.4%), experienced a fall from their chairs or tipped over. Of 85 deaths (11%) caused by environmental factors, stairs were implicated in 51 (60.0%). Of 48 fatal burns (6.2%), 27 (57.3%) were related to smoking. Asphyxia owing to restraints occurred in 44 persons (5.7%) of all ages and caused 10 of the 17 deaths (58.8%) among persons 1-20 yr old. Wheelchair-related accidental death is uncommon (about 0.2% of serious accidents per year), but some types of accidents appear to be preventable.