Search PubMed⌕ Search

Biomedical subjects

E F Gaffney

Publications and source records attributed to E F Gaffney.

At least 19 recordsLinked to original sources
PubMed2004

Morphologically distinct patterns of apoptosis correlate with size and high-grade dysplasia in colonic adenomas.

AIMS: To examine the relationship of morphological patterns of apoptosis in colonic adenomas to standard pathological variables. METHODS AND RESULTS: Apoptosis patterns were evaluated in 184 consecutive colonic adenomas and 14 adenocarcinomas, using haematoxylin and eosin sections. Apoptosis identification was selectively validated by electron microscopy. There were three patterns of apoptosis: (i) confluent basal apoptosis; (ii) crypt lumen apoptosis, both assessed semiquantitatively; and (iii) scattered apoptosis (not quantified). Adenoma site, size, type, mitoses, and grade of dysplasia were also assessed. MIB-1 immunostaining was performed in 20 cases. In 142 adenomas (77%) confluent basal apoptosis (n = 124) and/or crypt lumen apoptosis (n = 69) were identified; 42 (23%) had scattered apoptosis only. Significant correlations were: (i) extensive confluent basal apoptosis with small adenomas < or =5 mm (P < 0.0001); (ii) crypt lumen apoptosis with large adenomas >5 mm (P < 0.0001) and (iii) with high-grade dysplasia (P < 0.0003); and (iv) coexistence of both patterns (n = 51) with large adenomas >5 mm (P < 0.0001). Neither apoptosis pattern correlated with other variables. Adenocarcinomas had minimal confluent basal apoptosis (5/14), conspicuous crypt lumen apoptosis (14/14), intraglandular coagulative necrosis, and scattered apoptotic tumour cells. CONCLUSIONS: Confluent basal apoptosis is maximal early in colonic tumorigenesis. The 'switch' to a predominant crypt lumen apoptosis pattern suggests that a different apoptosis induction mechanism might be associated with the transition to adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Caspase 3 expression in benign prostatic hyperplasia and prostate carcinoma.

BACKGROUND: Apoptotic resistance to androgen ablation represents a significant problem in the treatment of prostate cancer. Over expression of antiapoptotic proteins such as Bcl-2 and mutations in p53 contribute to this resistance. The caspase family of proteases are central executioners of the cell death pathway. They are expressed in normal prostate secretory epithelial cells. Altered expression may represent an additional component leading to cell resistance. The aim of this study was to determine by immunohistochemistry caspase 3 expression in benign prostatic hyperplasia and prostate cancers. METHODS: Twenty-two patients with histologically determined prostate cancer and benign prostatic hyperplasia (BPH) were investigated. All specimens were obtained from patients undergoing surgical resection of the prostate. Immunohistochemical analysis was performed on formalin fixed paraffin embedded sections to assess caspase 3 expression. RESULTS: Caspase 3 was expressed in 18/22 (81.1%) samples, with high expression in BPH which demonstrated staining in both basal and secretory epithelial cells. Increasing grades of prostatic cancer showed a significant loss of expression in secretory epithelial layers and little staining in epithelial cells in high-grade prostatic carcinoma. CONCLUSIONS: Altered caspase 3 expression may represent an additional mechanism of apoptotic resistance to androgen ablation. Prostate 47:183-188, 2001.

Apoptosis↗
PubMed1999

Abl expression, tumour grade, and apoptosis in chondrosarcoma.

AIMS: To determine whether Abl immunoreactivity correlates with grade and cell kinetics (apoptosis and mitosis) in chondrosarcoma. METHODS: Sections from 16 chondrosarcomas were stained immunohistochemically using a polyclonal antibody to the c-Abl/Bcr-Abl oncoprotein. Apoptotic indices and mitotic indices were assessed in all tumours. Sections from 24 paraffin wax blocks of human fetal rib (gestational ages, 15-42 weeks) were also stained to determine whether the Abl protein is synthesised consistently throughout endochondral ossification. RESULTS: Abl staining in immature fetal rib chondrocytes at all stages of development was predominantly nuclear, and 70% of cells showed moderate to strong staining. Abl immunoreactivity was minimal or absent in hypertrophic chondrocytes about to undergo apoptosis at the growth plate. There was strong Abl staining in grade 1 and grade 2 chondrosarcomas but staining was greatly reduced or absent in grade 3 chondrosarcomas. There was a very significant linear correlation between apoptotic index (mean, 0.68%; range, 0-3.2%) and mitotic index (mean, 0.23%; range, 0-0.9%), and both indices were significantly lower in grade 1 than in grade 2 and grade 3 chondrosarcomas. CONCLUSIONS: These data suggest that abl gene expression is associated with differentiation and apoptosis inhibition in fetal and neoplastic chondrocytes. However, these putative effects cannot be ascribed solely to the Abl protein, because several additional factors contribute to the regulation of both differentiation and apoptosis.

Apoptosis↗
PubMed1998

Apoptosis: basic concepts and potential significance in human cancer.

Numerous factors trigger or repress apoptosis (genetically mediated individual cell death). The details of signal transduction pathways and regulation of apoptosis by numerous oncogene and tumor suppressor gene products are not fully understood. Bcl-2 inhibits apoptosis induction by a variety of stimuli. Caspases are the basic effectors of apoptosis, leading ultimately to fragmentation of DNA, at which stage apoptosis can be identified. Apoptosis affects scattered individual cells that have extremely dense nodular, beaded, or crescentic chromatin, and differs morphologically, biochemically, and topographically from necrosis. Apoptosis is a negative growth-regulating mechanism in cancer, and its extent varies with tumor type. Apoptosis reflects tumor cell kinetics; aggressive tumors often show conspicuous apoptosis, and there are significant linear correlations between apoptotic and mitotic indices in many tumor types. The relative importance of p53, c-Myc, Rb, and the Bcl-2 homologs in the regulation of apoptosis in different human cancers is not clear. Further pathologic investigations on apoptosis in human cancer are needed to reaffirm recent experimental findings and to explain more fully the regulation and biological significance of apoptosis in vivo.

Apoptosis↗
PubMed1997

Abl expression in human fetal and adult tissues, tumours, and tumour microvessels.

Abl kinases encoded by the abl oncogenes inhibit apoptosis without affecting cell proliferation. The aim of this study was to examine a wide range of normal fetal and adult human tissues and a variety of tumour types for Abl immunoreactivity. Sections from 193 paraffin blocks of normal fetal and adult tissues and 72 blocks from representative tumours were stained immunohistochemically using a polyclonal antibody to c-Abl/Bcr-Abl oncoprotein. Weak Abl immunoreactivity was observed in many adult tissues. Moderately intense or strong staining (cytoplasmic, nuclear or membranous) was consistently seen in hyaline cartilage, adipocytes, and ciliated epithelium. In fetal tissues, there was a broadly similar staining pattern, but Abl expression was also seen in muscle (all types) and occasionally in endothelial cells. The most intense staining was seen in sites of endochondral ossification and in the umbilical cord stroma. Negatively staining tissues included epidermis and squamous mucosa, lymph nodes, tonsil, spleen, hepatocytes, and adrenals. Most tumours showed focal or weak Abl immunoreactivity. The most intense staining was seen in chondrosarcoma, liposarcoma, and diffuse gastric (signet ring) adenocarcinoma. In the latter two tumour types, Abl expression was also observed in tumour microvessels. These results suggest that Abl not only functions as an apoptosis inhibitor, but also may have a role in connective tissue maturation and differentiation and in tumour growth and angiogenesis.

Adult↗
PubMed1997

Extent of apoptosis in ovarian serous carcinoma: relation to mitotic and proliferative indices, p53 expression, and survival.

AIMS: To assess the extent of apoptosis in ovarian serous carcinoma and to examine possible relations between apoptosis, cell proliferation, p53 overexpression, and patient survival. METHODS: Apoptotic and mitotic indices were obtained by examining haematoxylin and eosin stained sections from 30 patients with ovarian serous carcinoma. Apoptosis was also evaluated semiquantitatively by in situ end labelling of fragmented DNA. Expression of p53 and determination of Ki-67 labelling indices were based on immunohistochemical staining. Clinical details were obtained from patients' clinical records. For statistical analysis, Fisher's exact test, parametric (Pearson) linear correlations, and the Kaplan-Meier method were used. RESULTS: The mean apoptotic index was 1.3% (range 0.02-3.9%), the mean mitotic index was 0.4% (range 0.02-1.1%), and the mean Ki-67 labelling index was 16% (range 4-32%). There were significant correlations between the apoptotic and mitotic indices (p < 0.0205) and between the mitotic and Ki-67 labelling indices (p < 0.024). There was a significant correlation between a high apoptotic index and poor prognosis (p < 0.02). p53 was overexpressed in 16 cases but the extent of apoptosis and outcome were both independent of p53 status. CONCLUSIONS: These results suggest that regulation of apoptosis is an integral component of tumour cell kinetics in ovarian serous carcinoma, and that increased apoptosis is indicative of aggressive tumour growth. p53 expression did not correlate with altered apoptosis, but the possibility of an attenuated apoptotic response to subsequent DNA damage by anticancer agents is not excluded.

Adult↗
PubMed1996

Apoptosis occurs independently of bcl-2 and p53 over-expression in non-small cell lung carcinoma.

Certain oncogenes and tumour suppressor genes are known to modulate apoptosis. To investigate whether overexpressed bcl-2 and abnormally stabilized p53 are associated with reduced apoptosis in paraffin sections of non-small cell lung carcinoma, apoptotic, mitotic, and Ki-67 labelling indices were determined and correlated with bcl-2 and p53 immunoreactivity in 54 squamous cell carcinomas and 22 adenocarcinomas. Nineteen squamous cell carcinomas (35.2%) showed over-expression of bcl-2, but all 22 adenocarcinomas were bcl-2 negative. Thirty-seven squamous cell carcinomas (68.5%) and 13 adenocarcinomas (59.1%) showed p53 over-expression. Apoptotic tumour cells were identified among p53 positive and bcl-2 positive tumour cells. There was a significant linear correlation between apoptotic indices and mitotic indices. bcl-2 over-expression and p53 over-expression were not associated with attenuated apoptosis, or altered mitotic or Ki-67 labelling indices in either tumour type. Neither bcl-2 nor p53 was of prognostic significance. These results suggest that apoptosis in non-small cell lung carcinoma occurs independently, and is not modulated primarily by, bcl-2 or p53. It is likely that the effects on apoptosis of bcl-2 and p53 are countered by those of other oncogene products and/or additional factors that regulate apoptosis in vivo.

Adenocarcinoma↗
PubMed1996

Paraganglioma of the prostatic urethra. A report of three cases and a review of the literature.

OBJECTIVE: To determine the incidence and clinical presentation of prostatic urethral paragangliomas and to compare these findings with paragangliomas occurring in the other sites of the lower urinary tract. PATIENTS AND METHODS: The clinical records of three patients with prostatic urethral paragangliomas were reviewed, as was the histology of each specimen. The tumours were stained immunocytochemically with neuron-specific enolase, chromogranin, S100 protein, protein gene product 9.5, prostate-specific acid phosphatase and prostate-specific antigen. RESULTS: The three tumours occurred in elderly men, two of whom presented with haematuria, one of whom also had a vesical transitional cell carcinoma, and the third patient had obstructive symptoms due to co-existent prostatic hyperplasia. The histological appearances and immunocytochemical findings were consistent with paraganglioma. Treatment consisted of local excision and there were no recurrences or metastases at 5 and 6 years in two patients for whom follow-up was available. CONCLUSION: Urethral paragangliomas are rare tumours arising in elderly men and are hormonally inactive. Although haematuria may be the presenting symptom, it is important to exclude additional more common and possibly more sinister lesions such as transitional cell carcinoma. Local excision appears to be curative.

Aged↗
PubMed1995

Tumor type is a determinant of susceptibility to apoptosis.

Little quantitative data exist on the extent of apoptosis (genetically-mediated cell deletion) in different human tumor types. Hematoxylin and eosin-stained paraffin sections of 102 malignant tumors (58 types) were evaluated for apoptotic cells and apoptotic bodies, using the 40x objective with a calibrated eye-piece and avoiding necrotic zones. The percentage of apoptotic cells and apoptotic bodies in the total number of tumor cells examined was designated as the apoptotic index (AI) for each case. There was a wide range in the AI for different tumor types: 45 tumors had AI < 1% and 93 had an AI of < 7%. In 107 additional tumors (11 types), the AI was determined to be within the same low, intermediate, or high range as the index cases. Apoptotic nuclear material was usually more prominent than mitoses. These results suggest that each tumor type has a characteristic AI that reflects innate tumor cell susceptibility to undergo apoptosis. Additional data are needed to determine whether significant variations in AI correlate with altered proliferative indices, aberrant oncogene/tumor suppressor gene expression, and standard clinicopathologic variables.

Adenocarcinoma↗
PubMed1995

In situ end-labelling, light microscopic assessment and ultrastructure of apoptosis in lung carcinoma.

AIMS: To compare in situ end-labelling (ISEL) of apoptosis in lung carcinoma with quantitative and semiquantitative light microscopic assessment and ultrastructural observations. METHODS: ISEL of apoptosis was evaluated in 42 lung carcinomas (24 squamous cell carcinomas, 12 adenocarcinomas and six small cell carcinomas). Results were correlated semiquantitatively with the extent of apoptosis in haematoxylin and eosin stained sections, with apoptotic indices and with ultrastructural observations (nine cases). RESULTS: In each tumour type the extent of apoptosis identified by ISEL correlated with that observed on light and electron microscopy. Tumour cells undergoing apoptosis showed either uniform nuclear staining with a surrounding "halo" or peripheral nuclear membrane staining. The latter pattern was more prominent in small cell carcinoma and correlated ultrastructurally with early apoptosis. A variable proportion of apoptotic cells and apoptotic bodies were unlabelled. Necrotic tumour cells were weakly stained but were distinguishable from apoptotic cells. CONCLUSIONS: ISEL, if used in conjunction with standard methods for investigating apoptosis, is a useful adjunct to the investigation of apoptosis in human tumour tissue.

Adenocarcinoma↗
PubMed1994

Soft tissue and visceral sarcomas in Irish patients. Interim analysis of data obtained by the Dublin Soft Tissue Tumour Panel.

The Dublin Soft Tissue Sarcoma Panel was established in 1989 with a view to achieving a unified approach to diagnosis and management of soft tissue and visceral sarcomas. This interim report presents data on 265 prospectively-evaluated patients and on a separate retrospective series of 126 patients. The patients in the prospective series were treated by 93 different surgical and medical specialists. Tumours presented in all anatomic sites and ranged in size from 0.2 to 60 cm. Leiomyosarcoma was the commonest tumour type. Eighty-nine tumours were inoperable at clinical presentation. There was a consensus panel diagnosis in over 90%, non-neoplastic reactive lesions and primitive round cell tumours being the most difficult cases diagnostically. Management, including onward referral for chemotherapy or radiation therapy, was inconsistent. The 2-year survival figures were: 43% (1989-91) and 37% (1980-88). These findings should provide a basis for the evaluation of coherent treatment strategies for Irish sarcoma patients.

Adolescent↗
PubMed1994

The extent of apoptosis in different types of high grade prostatic carcinoma.

Apoptosis is the genetically mediated mechanism by which individual cells are deleted from living tissues. The extent of apoptosis in human tumours has not been examined in detail. In this study, apoptotic indices were assessed semiquantitatively by light microscopy in routine haematoxylin and eosin (H & E) stained sections of 15 high-grade carcinomas of the prostate by light microscopy, using the 40 x objective, counting 2000-2500 tumour cells per case. The mean apoptotic index for nine solid undifferentiated carcinomas was 1.7% (range 0.2-2.4%), for three small cell undifferentiated carcinomas 25.2% (range 10-37%), and for three secondary transitional cell carcinomas of the prostate 5.5% (range 2.4-9.1%). In general, apoptosis was easily identified, using the 40 x objective. There were minor variations in apoptosis from field to field in each tumour, and greater variability in the apoptotic index was observed among the small cell undifferentiated carcinomas and transitional cell carcinomas. In conclusion, assessment of apoptosis in routine H & E sections of human tumours is feasible, but it remains to be determined whether the extent of apoptosis correlates with other determinants of biological behaviour.

Apoptosis↗