PubMed Health⌕ Search

Biomedical subjects

F A Carey

Publications and source records attributed to F A Carey.

At least 19 recordsLinked to original sources
PubMed1998

Pulmonary adenocarcinoma: classification and molecular biology.

Pulmonary adenocarcinoma is increasing in incidence. Current classification systems based purely on morphological features are of little clinical relevance. Recent descriptions of genetic abnormalities, particularly in K-ras, p53, and c-erb-B2, may form the basis of a new taxonomy having direct prognostic relevance. Study of these molecular lesions has also helped to define a new pathway of tumourigenesis in the lung parenchyma, through alveolar atypical hyperplasia (AAH) to clinical adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Neuroendocrine differentiation in lung cancer.

The human lung has a resident population of neuroendocrine (NE) cells. These are characterised by the presence of neurosecretory granules and by a number of histochemical and immunocytochemical reactions. NE differentiation is a defining feature of classical and atypical carcinoid tumours and is seen in most small cell lung cancers (SCLC). Such differentiation has also been described in up to one third of non-small cell lung cancers (NSCLC). As demonstrated in an accompanying paper in this issue of the Journal, the reporting of NE differentiation varies with the technical approach used and with the nature of the tissue specimen. This phenomenon is a reflection of the histological and biological heterogeneity of lung cancer and has not been shown to be of clinical utility.

Carcinoid Tumor↗
PubMed1996

Lung tumours immunoreactive for parathyroid hormone related peptide: analysis of serum calcium levels and tumour type.

Secretion by tumours of parathyroid hormone-related peptide (PTHrP) in quantities sufficient to raise circulating levels results in the syndrome of humoral hypercalcaemia of malignancy (HHM). Since HHM is commonly associated with squamous carcinoma of lung and rarely with adenocarcinoma or lung neuroendocrine tumours, immunopositivity was related to tumour type, to assess whether this difference was due to a low general incidence of PTHrP expression in the latter two groups. Seventy-six of 82 tumours were immunopositive: 22 of 22 squamous carcinomas, 21 of 25 small cell lung carcinomas, 14 of 15 carcinoids, and 19 of 20 adenocarcinomas. These data confirm and extend previous observations on squamous and neuroendocrine tumours but are in contrast with previous findings in adenocarcinoma, which have suggested that only a small proportion of cases express the peptide. They suggest that the differences in incidence of HHM in the various tumour types are due to patterns of secretion, rather than differences in expression of PTHrP. The second aim of this study was therefore to assess whether tumours immunopositive for PTHrP, but not associated with HHM, might secrete PTHrP at levels which might result in more subtle changes in calcium metabolism. Preoperative calcium levels were analysed in a series of 56 patients with immunopositive lung tumours of all types. One small cell carcinoma was associated with hypercalcaemia, but there was no evidence of any other alteration in serum calcium. These data indicate that the majority of tumours expressing PTHrP do not secrete it in amounts sufficient to alter calcium metabolism.

Adenocarcinoma↗
PubMed1996

Loss of heterozygosity at 5q21 in non-small cell lung cancer: a frequent event but without evidence of apc mutation.

Four genetic polymorphisms in the APC and MCC genes at chromosome 5q21 were analysed for loss of heterozygosity (LOH) in 97 primary squamous carcinomas and adenocarcinomas of the lung. LOH was identified in at least two polymorphic loci in 41 percent of informative cases. There was no significant difference in the frequency of LOH between squamous carcinomas and adenocarcinomas. Within the adenocarcinoma group, however, LOH appeared to be more common in tumours having a bronchial origin (5/9; 56 per cent) than in parenchymal adenocarcinoma (6/21; 29 per cent). All 32 tumours showing LOH at one or more polymorphic sites were examined for mutations in the mutation cluster region (MCR) of APC by single-strand conformational polymorphism (SSCP) analysis. Mutations were not detected in any of these cases. We therefore propose that it is likely that a tumour suppressor gene on 5q other than APC is involved in the pathogenesis of lung cancer.

Adenocarcinoma↗
PubMed1996

A comparison of flow and image DNA cytometry in prediction of patient prognosis in surgically resected small cell lung cancer.

We have previously reported that flow cytometric tumor DNA content may be of prognostic significance in surgically resected small cell lung cancer (SCLC). We are particularly interested in determining prospective parameters for better selection of 'good prognosis' patients to proceed to surgery. Since flow cytometric measurements are poorly, if at all, applicable to endoscopic biopsy and cytology specimens we compared an image cytometric system to flow cytometry and clinical parameters in an extended series of surgically resected SCLC. Clinical follow-up was obtained on 75 patients having surgical resection for SCLC in the years 1981-92. Paraffin blocks were prepared for cytometry in standard fashion. Flow DNA histograms were characterised as diploid/tetraploid (n = 45) or DNA aneuploid (n = 27). DNA histograms obtained by image analysis were divided into type I (peridiploid n = 43) or type II (non-diploid with a minority of cells in peridiploid region; n = 31); 5c exceeding rate, 2c deviation index and malignancy grade were also computed. Overall two year survival was 27/75 patients (36%). Stage of disease was confirmed as a predictor of outcome with only 3/17 (18%) N2 patients surviving for 2 years as compared to 24/52 (46%) patients with N0/N1 disease. Image cytometric histogram classification just reached statistical significance with type I histograms indicating a better prognosis (20/43 survivors (47%) versus 7/31 (23%) patients with type II profiles, P < 0.05). Flow cytometry, 5cER, 2cD1 and malignancy grade were not useful in predicting prognosis. The results do not indicate a significant role for cytometry in SCLC.

Carcinoma, Small Cell↗
PubMed1995

Primary small-cell cancer of the esophagus.

Primary small-cell cancer of the esophagus is a rare tumor that disseminates early with a uniformly poor prognosis if untreated. Sixteen patients with malignant dysphagia referred to the Thoracic Surgical Unit, City Hospital, Edinburgh, within a 10-year period had a diagnosis of primary small-cell cancer of the esophagus. Seven patients underwent subtotal esophagectomy or esophagogastrectomy, either alone or with adjuvant chemotherapy or radiotherapy, with a mean survival of 20 months (standard deviation 35.4 months, range 2 weeks to 96 months). The remaining nine patients had disseminated disease when they were first seen and were treated symptomatically by intubation alone (1 patient), intubation and palliative chemotherapy or radiotherapy (3 patients), palliative chemotherapy (2 patients), palliative radiotherapy (1 patient), or no therapy (2 patients), with a mean survival of 4.8 months (standard deviation 2.6 months, range 2 to 9 months). Patients seen with this aggressive tumor should be assessed urgently for evidence of metastatic spread and then offered resection in combination with chemotherapy if they are otherwise fit for operation. This treatment regimen has given us one long-term survivor (96 months) who, we believe, is the only patient to have been cured of this condition. Patients seen with disseminated disease should have symptomatic treatment of the dysphagia combined with palliative chemotherapy.

Carcinoma, Small Cell↗
PubMed1995

Pulmonary actinomycosis--a master of disguise.

Three cases of pulmonary actinomycosis are described. In all three cases, an initial diagnosis of pulmonary malignant neoplasia was made. The correct diagnosis was made histologically after the three patients underwent either lobectomy or pneumonectomy. All patients recovered after appropriate therapy. Pulmonary actinomycosis should always be considered in the differential diagnosis of pulmonary neoplasia, especially in young adults.

Actinomycosis↗
PubMed1995

Interobserver variation in cell selection for DNA image cytometry.

AIMS: To describe a systematic investigation of interobserver differences in interpretation of nuclear morphology in preparations of small cell lung cancer (SCLC). METHODS: The screening/reviewing facility on the highly optimised microscope environment was used to individually tag 127 nuclei, chosen to reflect the spectrum of morphological appearances in nuclear preparations from three biopsy specimens of SCLC. Each nucleus was reviewed and labelled as control (lymphocyte), malignant or unsatisfactory by each of four observers. DNA histograms were plotted for each specimen using the nuclei identified as malignant by each participant. The histograms were compared in terms of identification of DNA stemlines and by calculation of a 5c exceeding rate (5cER). RESULTS: Interobserver variation in assessment of morphology was seen in 55.1% of nuclei. Disagreement occurred most frequently in the malignant/unsatisfactory category. Differences in morphological classification had little influence on histogram assessment by means of visual inspection but did show an effect on 5cER. CONCLUSIONS: There are significant interobserver differences in subjective assessment of nuclear morphology in cytometric preparations. This effect may seriously influence cytometric measurements.

Carcinoma, Small Cell↗
PubMed1994

Measurement of nuclear DNA content in histological and cytological specimens: principles and applications.

Nuclear DNA content can be measured in histological and cytological material by the techniques of image and flow cytometry. The measurement depends on the availability of stoichiometric markers for DNA. Results are expressed in DNA histograms from which tumour DNA ploidy and cell proliferation status can be estimated. Flow cytometry analyses large numbers of cells and gives the most meaningful cell cycle data. Image cytometry is more specifically targeted to the population of interest and can accurately measure rare events. A large body of literature exists relating DNA cytometry to clinical outcome, but there are considerable inconsistencies between clinical series which may be due, in many instances, to problems of histogram interpretation and tumour sampling. Rapid 'user-friendly' systems currently under development may increase the clinical acceptance of DNA cytometry.

Cell Nucleus↗
PubMed1994

Atypical alveolar hyperplasia: relationship with pulmonary adenocarcinoma, p53, and c-erbB-2 expression.

Atypical alveolar hyperplasia (AAH) has recently been described in human lungs in association with primary lung cancer, particularly adenocarcinoma. Unlike proximal bronchogenic carcinoma, peripheral (parenchymal) adenocarcinoma of the lung does not have a well-recognized progenitor lesion. Epidemiological morphometric, and cytofluorometric data in the literature suggest that AAH is a candidate premalignant entity. In this study, 97 AAH lesions were found in lungs resected from 29 patients (1-13 lesions per case, mean 3.5) being treated for presumed carcinoma (25/29 had adenocarcinoma). From a study case-load of 285 adenocarcinoma-bearing lungs, the AAH incidence was 8.8 per cent. Sections of 67 AAH lesions from 19 patients were stained using monoclonal antibodies against Ki67 (MIB1), p53 (DO7), and c-erbB-2 (NCL-CB11). Ki67 was expressed in up to 10 per cent of AAH nuclei. Thirty-nine lesions (58 per cent) showed stainable p53 protein, while five (7 per cent) expressed membrane c-erbB-2 oncoprotein. These latter five lesions were all strongly positive for p53, and both p53 and c-erbB staining was associated with increased cellular crowding and pleomorphism in AAH. These data demonstrate that AAH exhibits some genetic changes associated with malignancy and thereby support the hypothesis that AAH is premalignant.

Adenocarcinoma↗
PubMed1993

Expression of the pro-opiomelanocortin gene in lung neuroendocrine tumours: in situ hybridization and immunohistochemical studies.

Neuroendocrine tumours of the lung may be associated with the ectopic adrenocorticotrophin (ACTH) syndrome and may synthesize and secrete ACTH-related peptides in the absence of the syndrome. However, immunocytochemical analysis may not confirm these biochemical findings, particularly in small cell carcinoma, which is poorly granulated. To investigate further the morphological evidence for expression of the pro-opiomelanocortin (POMC) gene in neuroendocrine lung tumours, we have examined a series of 46 small cell carcinomas and 13 carcinoid tumours of the lung by in situ hybridization for POMC mRNA using a digoxigenin-labelled oligoprobe. We have compared the findings with the immunocytochemical detection of ACTH and beta-endorphin. In situ hybridization was positive in 15 of 46 small cell carcinomas (33 per cent) and in 8 of 13 carcinoid tumours (62 per cent). Immunocytochemical staining was positive in only one carcinoid tumour. These in situ hybridization studies have corroborated biochemical data indicating POMC gene expression in a high proportion of lung neuroendocrine tumours. This suggests that the low levels of expression detected by immunocytochemistry may be due to low levels of hormone storage. Multivariate analysis showed a weak negative association between POMC expression and survival in small cell carcinomas, although this did not reach statistical significance.

Adrenocorticotropic Hormone↗
PubMed1993

Synchronous primary lung cancers: prevalence in surgical material and clinical implications.

BACKGROUND: The prevalence of synchronous primary lung neoplasms in surgical resection specimens was assessed. The associated clinical features and prognostic implications were investigated. METHODS: All surgical resections for lung cancer performed during seven years were reviewed. Synchronous tumours were defined by the presence of more than one tumour mass in the lung, by differences in histological subtype, by the presence of separate bronchial origins, or by differences in DNA stemlines. Clinical data were abstracted from case notes and information from the tumour registry. RESULTS: Just under 2% of all surgical specimens in the study period contained more than one primary carcinoma. The patients did not differ clinically from the general population of patients having surgery for lung cancer. The overall prognosis was poor (mean survival 27 months) but was significantly better for patients with synchronous squamous carcinomas (mean survival 49 months). CONCLUSION: Synchronous primary lung carcinomas are associated with a poor prognosis except in patients having tumours only of squamous histological type.

Adenocarcinoma↗
PubMed1992

Expression of proliferating cell nuclear antigen in lung cancer: a systematic study and correlation with DNA ploidy.

Heterogeneity of expression of the proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically in 156 tissue samples from 33 surgically resected pulmonary carcinomas using the monoclonal antibody 19A2. The DNA content of each of these samples was measured by flow cytometry. Mean PCNA expression was higher in squamous carcinomas than in adenocarcinomas but there was marked intra-tumour variation in PCNA index in almost all cases. Intra-tumour heterogeneity of DNA content was noted in 11 cases. The PCNA index of these cases (34.1) was higher than that of DNA homogeneous cases (19.4). The wide variation in PCNA expression between different samples within a tumour would indicate that systematic sampling and counting will be necessary in future immunohistochemical studies of cell proliferation in tumour material.

DNA, Neoplasm↗
PubMed1992

Alveolar atypical hyperplasia in association with primary pulmonary adenocarcinoma: a clinicopathological study of 10 cases.

BACKGROUND: A distinctive cytologically atypical lesion has been found in patients with primary adenocarcinoma of the lung. The aim of this study was to characterise the lesion and assess its role in tumour pathogenesis. METHODS: Lung parenchyma from 175 consecutive resection specimens for primary pulmonary adenocarcinoma were examined. Foci of atypical hyperplasia were identified. Cell proliferation state and expression of S100 and carcinoembryonic antigens were evaluated by immunohistochemistry. Clinical data on cigarette smoking and occupational exposure to carcinogens were abstracted from inpatient case notes. RESULTS: Ten cases (5.7%) with these distinctive cytologically atypical lesions were identified. The lesions showed immunohistochemical evidence of increased cell proliferation and focal carcinoembryonic antigen expression. The associated adenocarcinomas were of peripheral (parenchymal) type. There was an association with cigarette smoking and two of the 10 patients had synchronous carcinomas elsewhere in the lung. CONCLUSION: The clinical and pathological associations of these lesions suggest that they may be important in the histogenesis of primary pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1992

Prognostic significance of tumor deoxyribonucleic acid content in surgically resected small-cell carcinoma of lung.

The prognostic role of deoxyribonucleic acid flow cytometry was investigated in 53 cases of surgically resected small-cell lung cancer. Deoxyribonucleic acid aneuploidy was detected in 26 patients (49.1%), the remaining tumors being either diploid or tetraploid. Patients with aneuploid tumors had a significantly reduced 2-year survival (38.5%) when compared with patients with diploid or tetraploid tumors (70.3%; p less than 0.05). This finding was independent of tumor stage on multiple logistic regression analysis. Diploid or tetraploid deoxyribonucleic acid content was associated with a particularly good 2-year survival (85%) in N0 or N1 disease. Tumor deoxyribonucleic acid ploidy should be taken into account in planning of management and assessment of prognosis in small-cell lung cancer.

Carcinoma, Small Cell↗