Damage to intracranial optic pathways in fatal closed head injury in man.

Head injury is a leading cause of visual impairment. This is partly due to direct trauma to the eye and optic nerve but much of the damage involves the intracranial optic pathways. We have studied the frequency, distribution and nature of the intracranial lesions of the optic pathways at autopsy in 45 cases of severe closed head injury, and examined the correlation between these post-mortem lesions and the ante-mortem clinical findings. Twenty-four of the patients had been involved in road traffic accidents. The ages ranged from 9 to 88 years (mean 46.4), the Glasgow Coma Score (GCS) on admission ranged from 3 to 15 (mean 5), and the survival time after injury from 2.5 h to15 days (mean 3.3 days). Skull fractures were present in 75.6% of the cases. Histological assessment included the use of immunohistochemistry for beta-amyloid precursor protein (beta-APP) and the microglial marker CD68. Axonal injury of varying severity was demonstrable in all cases, and in 39 (87%) the optic chiasm, tracts or radiations were involved, usually in more than one region. The severity of axonal injury was mild in 11 (24%), moderate in 9 (20%) and severe in 19 (42%) cases. The optic radiation at the level of the trigone of the lateral ventricle was particularly frequently and severely affected. The least affected parts of the intracranial optic pathways were the optic chiasm and the posterior segment of the optic nerve. The severity of injury to the optic pathways did not always reflect severity of axonal injury elsewhere in the brain and correlated poorly with the type of trauma (high- or low-velocity), presence of skull fractures or evidence of raised intracranial pressure (ICP). Of the 39 patients who survived more than 6 h, histological evidence of ischaemic injury to the primary optic cortex was present in 26 (67%) and was severe in 12. We conclude that the visual pathways are affected in a high proportion of patients with fatal closed head injury, nerve fibres in the optic radiations being particularly vulnerable. The findings suggest that damage to the posterior parts of the optic pathways may be under-diagnosed among patients with head injury.

Labelling of breast carcinoma, thyroid carcinoma and melanoma with manno- and galacto-specific lectins from marine invertebrates.

Three marine invertebrate FITC-labelled lectins, CNL, GCL, and GSL, isolated respectively, from the sponges Chondrilla nucula, Geodia cydonium, and the hexacoral Gerardia savaglia, were used as potential diagnostic tools for different breast tumors. The lectins vary in their carbohydrate binding properties: GSL is D-mannose specific, GCL and CNL D-galactose specific. GSL labels most investigated types of malignant tissues distinctively, while the results with CNL and GCL are less consistent. The well known D-mannose specific lectin, concanavalin A, also binds to tumor tissues, but with much lower intensity than GSL.

Diffusely infiltrating endometrial carcinomas with no stromal response: report of a series, including cases with cervical and ovarian involvement and emphasis on the potential for misdiagnosis.

Endometrial carcinomas, particularly of endometrioid type, can invade the myometrium or cervix without eliciting a stromal desmoplastic or inflammatory response and have been referred to as diffusely infiltrating endometrial carcinomas. This study describes a series of 14 endometrial carcinomas infiltrating as single "naked" glands without a stromal response. The neoplasms consisted of 12 endometrioid carcinomas, 1 mixed endometrioid and clear cell carcinoma, and 1 serous carcinoma. In all cases, there was myometrial invasion without stromal response. Seven cases exhibited cervical stromal involvement and in 2 there was involvement of both ovaries in a similar pattern. Several of the cases were seen in consultation and the pattern of infiltration raised a number of differential diagnoses, both benign and malignant, depending on the site of tumor involvement, including adenomyosis, adenomyoma, primary endocervical glandular lesions, cervical mesonephric remnants, endometriosis or tuboendometrioid metaplasia, and ovarian cortical inclusion cysts. Although this pattern of invasion has been reported previously, it continues to present diagnostic difficulties.

Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting.

hnRNP B1 expression in benign and malignant lung disease.

Evidence is accumulating to suggest that hnRNP B1 expression may be a useful tool in the early diagnosis of lung cancer. This study examined the immunohistochemical expression of hnRNP B1 in archived sections of resected lung cancers and compared the patterns of expression with those seen in similar archived sections of non-neoplastic lung. Particular attention was paid to the expression of hnRNP B1 in the benign bronchial cells in both cases, to establish if overexpression of this protein in respiratory epithelial cells is specific for malignancy. Nineteen cases of different types of non-small cell carcinoma were examined (eight squamous cell, six adenocarcinomas, two carcinosarcomas, two undifferentiated large cell carcinomas, and one mucoepidermoid carcinoma) and compared with sections from 16 open lung biopsies (three cases of cryptogenic fibrosing alveolitis, two cases of sarcoidosis, two cases of organizing pneumonia, and one case each of tuberculosis, extrinsic allergic alveolitis, non-specific interstitial pneumonitis, pneumocystis pneumonia, aspergilloma, respiratory bronchiolitis-interstitial lung disease, mineral dust disease, Sjögren's syndrome and systemic sclerosis vascular variant). All the tumours showed positive staining, with the vast majority, 16/19 (84%), showing strong diffuse nuclear staining. The background cells of these cases showed positive staining in alveolar macrophages, lymph node germinal centres, bronchial mucous glands, and bronchial epithelial cells. No significant difference was seen in the percentage of positive bronchial epithelial cells in bronchi adjacent to the tumour compared with the resection margins. In the benign lung cases, positive bronchial epithelial cells were seen in a small percentage, 3/16 (18%), of cases, but the majority of cases showed no or very focal staining. The levels of expression between benign epithelial cells of malignant cases, compared with benign, showed a significant difference when the staining was assessed in percentage of positive nuclei (p = 0.001, Fisher's exact test). The results confirm that hnRNP B1 is widely expressed in a range of lung carcinomas; that expression is seen in benign bronchial epithelial cells and inflammatory cells; and that expression in background bronchial epithelial cells appears to be higher in malignant than in benign lung disease. It is feasible that this biomarker may be of use in the detection of early lung cancer, provided that levels of expression can be accurately quantified.

Interferon-a2b reduces neo-microvascular density in the 'normal' urothelium adjacent to the tumor after transurethral resection of superficial bladder carcinoma.

BACKGROUND: As angiogenesis represents one of the hallmarks of cancer we investigated whether intravesically administered interferon-a (IFN-a2b) reduces neo-angiogenesis in the 'normal' urothelium adjacent to the tumor in patients with superficial bladder carcinoma after complete transurethral resection (TUR) of the tumor. PATIENTS AND METHODS: In the present study 47 patients after TUR of the tumor were examined. 10 patients (group A) received no further treatment (control group); 37 patients (group B) received intravesical treatment with IFN-a2b. The instillations started within 7 days after TUR, were performed weekly for 2 months, twice a month for the next 4 months, and thereafter monthly for 6 more months. Cold cup biopsies were taken before TUR of the transitional cell carcinoma (TCC): from the tumor (T), near tumor (NT) and from normal epithelium (N). Cold cup biopsies 'near tumor', were also taken during follow-up cystoscopy (C1, C2, and C3) 2, 6, and 12 months after TUR, respectively. Angiogenesis was estimated by counting the microvessels detected with CD31 immunostaining. RESULTS: Significant differences of microvascular density (MVD) between patients of group A and B appear after TUR (p < 0.005, Kruskal-Wallis and Wilcoxon test). The MVD difference was maximal 6 months after TUR (C2(A)-C2(B), second cystoscopy) and measured at 12.17 microvessels/ mm(2) (26.2%). CONCLUSION: Our results show that the intravesical administration of IFN-a2b after TUR significantly decreases the angiogenic potential of the 'healthy' urothelium adjacent to the tumor in patients with TCC. This observation could possibly explain, to a certain extent, the mechanism by which IFN-a2b reduces the recurrence rate of primary TCC.