Biomedical subjects

N J Agnantis

Publications and source records attributed to N J Agnantis.

At least 73 records · Page 4Linked to original sources

PubMed1999

Glycoprotein CD44 expression in benign, premalignant and malignant epithelial lesions of the larynx: an immunohistochemical study including correlation with Rb, p53, Ki-67 and PCNA.

CD44 is an integral membrane glycoprotein that has diverse functions in cell-cell and cell-substrate interactions. It has been suggested that it may be a determinant of metastatic and invasive behavior in carcinomas. The immunohistochemical expression of CD44 was examined in a series of 34 squamous cell carcinomas, 13 in situ carcinomas, 35 cases with various degrees of epithelial dysplasia, 10 papillomas and 17 cases of keratosis. We used the monoclonal mouse anti-human phagocytic glycoprotein-1 CD44 (clone DF 1485), on formalin-fixed, paraffin-embedded tissue. CD44 expression was correlated with the expression of Rb and p53 proteins, with the proliferative indices Ki-67 and PCNA as well as with conventional clinicopathological data. The mean value of CD44 expression was 78.84 in squamous cell carcinomas, 78.04 in situ carcinomas, 54.93 in dysplasia, 26.8 in papillomas and 24.97 in keratosis. There was no significant difference of CD44 expression between in situ and invasive carcinomas. However, a strong difference of reaction between carcinomas and the other cases was observed. CD44 expression was statistically higher in dysplastic lesions than the cases of keratosis (p < 0.0001) and papillomas (p = 0.01). In the group of invasive carcinomas, CD44 expression was statistically correlated with pRb (p = 0.011), while in preinvasive lesions it was correlated with PCNA (p = 0.016). The relationship with the degree of dysplasia or grade of carcinoma and p53 protein expression was insignificant. These observations suggest that CD44 expression may be involved in the multiple mechanism of the development and progression of laryngeal lesions and may help to predict the risk of transformation of the benign or precancerous lesions to cancer.

Animals↗

PubMed1999

[Apoptosis and cancer].

Apoptosis or programmed cell death is a form of regulated cell death that represents an important biological principle in tissue development and homeostasis. Its regulation appears to be perturbed in several major diseases, including cancer. The control of cell death events is extremely complex at the genetic and biochemical levels. It has been suggested that genes or factors that suppress apoptosis are essential components of carcinogenesis. The complete mechanisms implicated in apoptosis remains an issue for a future investigation. Details of how the death pathway itself is initiated, will provide a firm basis for the development of agents capable of eliciting the process in chemoresistant tumours.

Apoptosis↗

PubMed1999

Analysis of chromosomal aberrations in breast cancer by comparative genomic hybridization (CGH). Correlation with histoprognostic variables and c-erbB-2 immunoexpression.

The establishment of additional powerful prognostic markers in breast cancer patients is of unquestionable importance given that breast cancer is characterized by morphologic, biologic and genetic heterogeneity. In the present study we analyzed 8 primary invasive breast carcinomas by comparative genomic hybridization (CGH) in order to find and map the DNA copy number changes occurring in these tumors. Furthermore, in order to evaluate the potential prognostic significance, we compared these genetic changes with other histo- and immunopathologic prognostic variables, such as tumor type, tumor grade, lymph node status, estrogen receptors content and c-erbB-2 oncoprotein expression. All the studied cases showed a wide variety of gains and losses of chromosomal regions or arms distributed among 16 chromosomes with an average number of 6.12 aberrations per case. Although several genetic changes appeared to be common, none was unique or consistent in all the studied cases. The most consistent regions of gain were on 1q, 20q and 8q while the most common regions of loss on 3p and 6q. Accumulation of chromosomal changes were more frequently found in high grade ductal breast carcinomas with overexpression of c-erbB-2 oncoprotein in both lymph node-negative and lymph node-positive patients, whose tumors were positive for estrogen receptors. If any of these genetic changes identified by CGH in breast cancer patients carry prognostic information, regardless of stage or other factors predictive of biologic behavior, further investigation is needed.

Adult↗

PubMed1998

Local immune response after intravesical interferon gamma in superficial bladder cancer.

OBJECTIVE: To investigate the lymphocyte subpopulations (T4, T8 and macrophages) and major histocompatibility (MHC) II antigens in patients with superficial bladder cancer before and after intravesical instillations of recombinant interferon-gamma (IFN-gamma). PATIENTS AND METHODS: Four intravesical weekly instillations of either 1.3 mg (20 patients, group A) or 0.7 mg (11 patients, group B) IFN-gamma were administered in 31 evaluable patients (28 men and three women, mean age 68.5 years). The CD4+, CD8+, CD68+ and HLA-DR antigens were detected immunohistochemically in tumours and a marker tumour before and after intravesical instillations. RESULTS: The median number of T4 lymphocytes increased from 15 per high-power field (HPF) to 27.5 in group A (P = 0.0029) and to 45 in group B (P = 0.0117). Macrophages increased from 6 cells/HPF to 15 cells/HPF in group A (P = 0.0029) and from 2 to 8.75 cells/HPF in group B (P = 0.0117). The T8 lymphocyte subpopulation decreased from 4 to 3 cells/HPF (P = 0.0231) in group A and from 5 to 2 cells/HPF (P = 0.0759) in group B. The median percentage of HLA-DR antigens increased from 1.5% to 18% in general, (P < 0.001), from 2.5% to 15% in group A (P = 0.0064) and from 0% to 20% in group B (P = 0.0077). The induction of HLA-DR antigens was statistically significant in those receiving the lower dose (from 0% before instillation to 20% afterward, P = 0.0277), while it was not with the higher dose (from 0% to 5%, P = 0.068). Irrespective of the dose of IFN used. T4 lymphocytes and macrophages increased significantly after treatment in patients in whom the tumour HLA-DR antigens were either up-regulated or remained stable. The median net increase in T4 cells was 17.5 and 30 cells/HPF for groups A and B, respectively (P = 0.0429). CONCLUSION: T4 lymphocytes, macrophages and HLA-DR antigens increased after intravesical IFN-gamma in patients with superficial bladder cancer, but T8 lymphocytes decreased. Irrespective of the drug dose used, patients with either upregulated or stable HLA-DR antigens after treatment showed the same pattern of changes in the lymphocyte subpopulations. The two doses generally had the same effect on the immunological variables assessed but the lower dose was more effective in inducing HLA-DR antigens and in increasing the number of T4 lymphocytes in the tumours.

Administration, Intravesical↗

PubMed1997

Immunohistochemical expression of cathepsin D in correlation with extracellular matrix component, steroid receptor status and proliferative indices in breast cancer.

In 87 breast cancer patients, the immunohistochemical expression of the basement membrane (BM)-degrading enzyme cathepsin D (CD) was correlated with the expression of extracellular matrix components, with growth fraction, steroid receptor content and with the other conventional prognostic variables in breast cancer. Only 6.25% of tumours had laminin-defined BM, while 86.8% showed staining for fibronectin. CD was also identified in carcinoma cells (cancer cell CD; CCCD) and in stromal cells (stromal cell CD; SCCD). Forty-five percent of tumours showed CCCD and 47.5%, SCCD expression. CCCD expression was significantly correlated with positive oestrogen receptor content, with low Ki-67 and high PCNA score and with SCCD expression. There was no correlation with collagen type IV, laminin or fibronectin. SCCD expression was positively correlated with collagen type IV, laminin expression and tumour grade. The data suggest that the CD of tumour cells and the CD of tumour-associated macrophages have different roles in breast cancer. CCCD correlates with cell proliferation and is regulated by oestrogens, while SCCD relates to cell differentiation, is oestrogen-independent, and has a proteolytic role in the breakdown of BM components.

Breast Neoplasms↗

PubMed1997

p53 and c-jun expression in urinary bladder transitional cell carcinoma: correlation with proliferating cell nuclear antigen (PCNA) histological grade and clinical stage.

OBJECTIVE: To investigate p53 and c-jun oncoproteins and proliferating cell nuclear antigen (PCNA) in transitional cell urinary bladder carcinomas (TCCs) and to determine their relationships to tumour grade, stage and survival. MATERIALS AND METHODS: The expression of p53, c-jun and PCNA was studied using immunohistochemistry in formalin-fixed, paraffin-embedded tissues in a series of 110 TCCs. RESULTS: 58% of our cases were positive for p53 and 88% for c-jun. A statistically very significant correlation (p < 0.0001) was observed between p53 and c-jun (r = 0.781), p53 and PCNA (r = 0.772), c-jun and PCNA (r = 0.831) as well as between each of the two oncoproteins and the histological grade and clinical stage (p < 0.001). There was no correlation of either p53, PCNA or c-jun with clinical outcome in terms of patients survival. CONCLUSION: p53 and c-jun proteins' overexpression are strongly related to rapid tumour cell proliferation and hence with aggressive growth in urinary bladder TCC. PCNA score remains an important prognostic index in transitional cell carcinoma of the bladder.

Antibodies, Monoclonal↗

PubMed1996

Diagnostic accuracy of pericardial fluid cytology: an analysis of 53 specimens from 44 consecutive patients.

Over a 7-yr period, a total of 53 pericardial fluid specimens from 44 patients was examined. A correlation between cytological and histological diagnosis was made in 19 of these cases. In the remaining 25 cases, where a biopsy was not performed, the cytological diagnosis was correlated with the final clinical diagnosis and the patients' clinical outcome. Finally, in 9 out of 14 cases of malignancy where both cytological and a histological diagnosis was made, the cytologic prediction of the histologic type of cancer was evaluated. The overall sensitivity was 100%, the overall specificity was 93.3%, and the overall cytological accuracy was 95.4%. The predictive value of the correct histologic type of cancer by cytology was 77.7%. Our findings show that the careful cytomorphological examination of pericardial fluid aspirates is a valuable, reliable, and diagnostically highly accurate method, which could be performed on a routine basis in a busy cytopathology department. Judiciously chosen ancillary procedures, as well as clinicopathological correlation, are of great value for an accurate diagnosis in problematic cases.

Adolescent↗

PubMed1996

p53 expression in hepatocellular carcinoma in Greece. Correlation with epidemiological and histopathological data.

Localization of p53 oncoprotein was investigated in 60 hepatocellular carcinomas (HCCs) from patients resident in the Northwest and Central Greece. The streptavidin-biotin complex immunoperoxidase method was performed in archival formalin-fixed, paraffin-embedded material, using the monoclonal antibody DO-1. The aim of our study was to correlate p53 expression with histological and epidemiological data. p53 overexpression in patients with serological hepatitis B or C was greater (47%) as compared to that observed in patients without these markers (p < 0.01). Morphologically normal liver tissue (NLT) and liver cell dysplasia (LCD) was recognized adjacent to HCC developing on non-alcoholic cirrhotic livers in patients with "NonA, NonB hepatitis" from between 1975-1986. NLT and LCD and p53 oncoprotein was expressed in 10% of the cases. No relationship was observed between p53 expression and tumor histological grade, patients' age and sex. These results suggest that in Northwest and Central Greece, p53 oncosupressor gene may be involved in some HCCs; it may be associated with viral chronic infection disease (HBV or HCV), and as yet with uncharacterized viruses which remain to be determined.

Adult↗

PubMed1995

Distribution of CD1a-positive Langerhans cells and lymphocyte subsets in transitional cell carcinoma of the urinary bladder. An immunohistological study on frozen sections.

The distribution of CD1a-positive Langerhans cells, CD4-positive T-helper cells, and CD8-positive T-suppressor cells in 36 patients with transitional cell carcinoma of the urinary bladder was studied immunohistochemically on frozen sections. Multiple tissue specimens from the tumour, the adjacent mucosa, and random bladder wall biopsies were examined. Langerhans cells were mainly interspersed among the tumour cells, whereas T-helper cells were present in aggregates in the stroma. T-suppressor cells were present both in aggregates in the stroma and among the tumour cells. There was a marginal relationship between the density of Langerhans cells and the density of T-helper/inducer cells and a good relationship with CD8-positive cells. There was no statistically significant difference in the population density of Langerhans cells associated with the various clinicopathological variables, including growth pattern, histological grade and stage, or patient's age and sex. On the contrary, a statistically significant difference was found in the CD1a/CD4 ratio among specimens of different grades. These results show that CD1a cell populations correlate with T-cell populations in bladder cancer, suggesting that Langerhans cells take part in the immune response carried out by T lymphocytes, their task being apparently antigen presentation.

Adult↗

PubMed1994

HLA-DR antigen expression and lymphocyte subsets in transitional cell carcinoma of the urinary bladder. An immunohistological study on frozen sections.

Lymphocyte subpopulations (B cells, CD4, CD8), interleukin-20 receptors (IL-2), monocytes/macrophages (Leu M5), and HLA-DR antigen expression were studied immunohistochemically on frozen sections from 38 bladder cancer specimens. T cells predominated over B cells in all tumours. CD4-positive lymphocytes predominated over CD8 in the stroma (CD4/CD8: 1.35/l), while in epithelial tumour cells CD8 was the prominent subpopulation (CD8/CD4: 1.75/l). Aberrant HLA-DR expression was found in 21.05 per cent of bladder tumours. A strong correlation between CD4 and CD8 population densities and macrophages with the other subpopulations was noticed. In HLA-DR-positive tumours, there was no correlation of the percentage of positive cells with CD4- and CD8-positive lymphocyte populations. Various parameters including IL-2 receptors, B cells, CD8- and CD4-positive cells, and macrophages did not differ significantly between the groups of tumours expressing and not expressing HLA-DR antigen. There were no statistically significant differences in the population densities of B cells, CD8- or CD4-positive cells, IL-2 receptor, monocytes/macrophages, and HLA-DR antigen expression among various clinicopathological parameters, including growth pattern, histological grade and clinical stage or patient's age and sex. These findings suggest that in transitional cell carcinoma of the urinary bladder, HLA-DR antigen expression is independent of lymphocyte subpopulations. It is therefore possible that HLA-DR expression by tumour cells reflect the existence of separate HLA-DR-positive or HLA-DR-negative tumour clones.

Adult↗

PubMed1994

Histological findings in breast tissue specimens from reduction mammoplasties.

Tissue specimens from 55 consecutive reduction mammoplasty operations were studied histologically for changes considered to be associated to an increased risk in the development of invasive breast cancer. A thorough sampling of all removed tissues was performed and nearly all solid parts were processed for histological evaluation. We found that in 47 specimens, most of which belonged to women younger than 40 years of age (39), both breasts presented either no-proliferative changes or mild hyperplastic lesions of the usual type and thus the women had no increased risk for breast cancer development. In 7 breast specimens, all of them from women older than 30 years, the changes observed ranged from florid hyperplasia to atypical ductal or lobular hyperplasia, which are lesions considered to be associated to a relatively increased risk of invasive carcinoma. Finally we present a case of infiltrative ductal carcinoma with extensive lesions of atypical hyperplasia and combined ductal and lobular carcinoma in situ in both breasts, which developed 3 years after reduction mammoplasty in which changes of atypical hyperplasia were found. We suggest that reduction mammoplasty specimens should be handled with particular care and according to the women's age.

Adolescent↗

PubMed1992

Pleomorphic adenoma of the human female breast.

We are presenting an interesting rare benign breast tumor which meets the characteristics of a salivary gland pleomorphic adenoma. The tumor was misdiagnosed during frozen section procedure, because several clusters, mainly composed of myoepithelial cells and surrounded by a chondroid matrix, were mistaken for cancerous blasts. Additionally the clinical and mammographic findings were very suspicious. Although this particular tumor is very infrequent, the pathologist should be aware of the difficulties in the differential diagnosis during frozen section and thus defer his final answer to the paraffin sections.

Breast Neoplasms↗

PubMed1992

Immunohistochemical expression of subunit beta HCG in breast cancer.

The ectopic production of HCG by non-trophoblastic tumors is well documented. Adenocarcinomas arising in the mammary gland have been shown to stain positively for the beta subunit of HCG using immunoperoxidase technique. In the present study we used the Monoclonal antibodies (M. abs) H6, H34 and H54 directed against the subunits of this hormone. A total of 31 breast tissue sections from formalin fixed, paraffin embedded unselected material was examined, out of which 22 concerned different types of primary breast cancer (Ca), 5 local recurrences, 3 cystic disease (CD) and one was an axillary lymph node metastasis (LNM). All cases were evaluated for cytoplasmic localization of the beta subunit HCG using the Mab H36 and among the 27 breast Ca 9 were studied with Mab H34 and 6 with Mab H54. Our results with the Mab H6 showed the following: 1) 55.5% of the Ca including the recurrences, were strongly positive (+) and 18.5% weakly positive (+/-); 2) 63.6% of the Grade III tumors were negative (-), whereas 81.2% of the Grade II were +, 18.7% +/- and none was -; 3) It seems that by increasing infiltration of the tumor size positivity is increased; 4) Lymphocytic infiltration of the tumor stroma and LNM did not appear related; 5) From the FU data of 14 cases collected up to now, the 10-year-survival seems to be inconclusive; 6) The 3 cases of CD were negative except for the apocrine cells which were positive; 7) The unique axillary LNM was positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1992

Immunohistochemical study of ras and myc oncoproteins in apocrine breast lesions with and without papillomatosis.

We have previously employed different immunohistochemical procedures for the study of breast disease in the human. The use of the monoclonal antibodies (M. Abs) against protein products of the ras and c-myc oncogenes has shown that the respective oncoproteins are expressed not only in the cancer cases but also in the majority of complex cystic diseases (C.C.D.). The term C.C.D. is used when cystic disease is associated with epithelial hyperplasia and cellular atypia but without malignant transformation. Additionally, the degree of staining intensity is increasing when the latter is associated with papillary apocrine metaplasia, which is included in the group of epithelial hyperplasias. In the present study we examined 50 cases of C.D. 20 of which were present in infiltrating duct carcinomas of non otherwise specified (NOS) type and the remaining 30 concerned benign biopsy material. We divided C.D. into simple (S.C.D.) and complex (C.C.D.) and we focused our interest on the presence or absence of papillary hyperplasia in apocrine metaplastic lesions. The whole material (50 cases) was examined immunohistochemically for the c-myc p62 protein using the M.Ab. Myc 1-9E10, and 21 cases were also examined for the ras p21 protein using the M.Ab. Y13 259. Our results imply that the great majority of C.D. show elevated expression of both c-myc p62 and ras p21 when associated with apocrine metaplastic papillary proliferations. Our results suggest that the levels of the expression of ras and myc oncoproteins may serve as premalignant markers for the prevention of the disease.

Antibodies, Monoclonal↗

PubMed1992

Chromosome aberrations and expression of ras and myc oncogenes in leiomyomas and a leiomyosarcoma of the uterus.

Twenty eight leiomyomas and one leiomyosarcoma were cytogenetically analysed and also examined for ras and myc oncoprotein expression. Chromosome alterations were found in seven leiomyoma cases. In four of them 12q14-15 was involved. P21 product of H-ras and P62 product of c-myc genes were detected in paraffin embedded parallel tissue sections. A high expression of H-ras was apparent in most tumors. C-myc expression was weak or negative in most leiomyomas with normal karyotype while on the contrary in three out of seven cases with abnormal cytogenetic findings the gene product stained moderately positive. Considerable chromosome abnormalities and oncogene overexpression were also identified in the leiomyosarcoma.

Adult↗

PubMed1991

Immunohistochemical detection of ras p21 and c-myc p62 in colonic adenomas and carcinomas.

In the present paper we review the results of our study on the use of monoclonal antibodies Y13,259 to the ras p21 and MYC1 9E10 to the c-myc p62 oncoprotein products in human tumors and tumorlike conditions of the colorectum. A total of 78 tissue sections were analyzed immunohistochemically and revealed the following: 42 adenocarcinomas with 8 normal mucosae adjacent to the tumor, 25 adenomas (with or without dysplasia and with in situ carcinoma) and 3 hyperplastic polyps. Parallel tissue sections were used in order to compare ras and c-myc oncoproteins. Reviewing our results we made the following remarks: 1. All adenocarcinomas but one were expressed with both oncoproteins, most of them being strongly positive. 2. All adenomas were positive for ras p21, and all but two were also positive for c-myc p62. An interesting point is that the degree of staining intensity increased in accordance with the degree of dysplasia and/or in situ carcinoma association. 3. The hyperplastic polyps, as well as all normal mucosae were negative.

Adenoma↗

PubMed1990

Immunohistochemical study of the ras oncogene expression in human bladder endoscopy specimens.

We have used the monoclonal antibody Y13 259 to the ras oncogene p21 protein product in 42 endoscopy specimens from the bladder of 37 patients, in order to determine the ras oncogene expression in different conditions of the urothelium. The examined material included: 27 normal and hyperplastic or dysplastic mucosae and 13 papillomas and transitional cell carcinomas, graded according to Mostofi's classification. Our results showed the following: the normal urothelium sections tended to be negative, while the umbrella cells from the superficial layer always expressed a higher degree of positivity. The majority of the hyperplastic lesions and the papillomas were weakly positive or negative. In contrast, all the dysplastic lesions and the carcinomas of different grades were strongly positive. Our results suggest that elevated expression of ras oncogene may serve as an early marker in the pathogenesis of bladder lesions.

Antibodies, Monoclonal↗

PubMed1988

The reliability of histologically negative axillary lymph nodes in breast cancer. Preliminary report.

In an effort to evaluate the reliability of negative axillary lymph nodes in breast cancer patients, we did recuts in three levels in order to detect occult metastases. Our material consisted of 50 breast cancer cases with negative axilla. From each lymph node two routine sections were reviewed. Consequently, we examined six additional sections from the recuts. Out of the 50 cases, 7 (14%) had occult metastases in one or more section. Our results suggest that a negative axilla in the routine study can show in a considerable percentage occult metastases corresponding to the number of recuts. This means that a sufficient number of patients have only theoretically negative axillary lymph nodes and for that reason may show a low survival rate and a worse prognosis than the one expected. On the other hand, the need for axillary dissection or the appropriate postoperative treatment for carcinoma of the breast is supported.

Adult↗