Biomedical subjects

N J Agnantis

Publications and source records attributed to N J Agnantis.

At least 91 records · Page 5Linked to original sources

PubMed1988

Immunohistochemical study of ras oncogene expression in endometrial and cervical human lesions.

The Y13 259 monoclonal antibody to the ras p21 protein was used in an immunohistochemical assay to study the levels of ras p21 in human uterine lesions as compared to normal tissue. Out of 73 hysterectomies obtained we have examined ras p21 expression in separately made sections from the endometrium, the cervix and leiomyomas found in the same specimens. A total of 155 tissue sections were finally evaluated and included: 55 endometrial mucosae (normal, hyperplastic and atrophic), 13 leiomyomas, 60 cervicitis (mild, moderate and severe with or without dysplasia), 3 in situ and 7 invasive carcinoma of the cervix, 12 invasive adenocarcinoma of the endometrium and 5 endometrial adenocarcinomas, which involved the cervical canal. Out of the 73 hysterectomy specimens 27 lesions were malignant and showed elevated expression of ras p21. The remaining 128 were normal or atrophic mucosae and benign or premalignant lesions, which were mostly negative. However, all cases of severe cervicitis and dysplasias and 6 out of the 12 hyperplastic endometrial lesions were found to be moderately or highly positive. Our results suggest that elevated expression of ras oncogenes may play an important role in the development of human uterine lesions.

Antibodies, Monoclonal↗

PubMed1987

[Breast cancer in adipose breasts].

The authors have studied breast cancer in fatty breasts in an attempt to prove their observations that Wolfe's classification "N1" on mammography was not necessarily "normal". Two groups of women, the first called group "A" consisting of 384 women with cancer of the breast, and group "B", the control group of 400 women who had no abnormality in the breast, were studied and correlated for epidemiological, thermographic, mammographic, and anatomo-pathological parameters. The following epidemiological factors were studied: age, marital status, profession, age at menarche and at menopause, menstrual behaviour, age at the first pregnancy that went to term, parity (live and still births), type of delivery, length of breast feeding, number of abortions, use of hormones, and family history of cancer of the breast. In the thermographic studies: the topography of the heat pattern, the primary pathological signs and the thermic state were studied. In mammography: the mammographic appearance after Wolfe and the presence of microcalcifications was studied. In group "A" the following histological group parameters were studied: which breast, in which quadrant the nodule was situated, the type of breast the contour and size of the tumour, the number of axillary nodes removed, the histological type of the cancer, the histological grade of the malignancy, vascular invasion, details about the skin and the areola, calcifications, lymphocytic infiltration of the stroma, multicentricity, the co-existence of cystic disease of the breast and invasion of the axillary nodes. All these above-mentioned parameters were correlated with: the age, the existence of previous pregnancies at term, the macroscopic type of the breast and the mammographic type according to Wolfe. The breasts were divided into three macroscopic types: fatty, fibrous and intermediate. The correlation of the mammographic type according to Wolfe showed that types N1 and P1 corresponded to fatty and partially intermediate types. In group "A" the macroscopically fatty as compared with the other type of breasts showed a more extensive degree of infiltrations: vascular (76.5%), skin (90.3%), areolae (88.9%) and lymphocytic (80.1%), as well as a higher percentage of axillary metastases (57.7%).

Adipose Tissue↗

PubMed1986

Comparative study of Harvey-ras oncogene expression with conventional clinicopathologic parameters of breast cancer.

We have previously examined the expression of the Harvey-ras (Ha-ras) oncogene related transcripts in human malignant breast tumors and in their respective normal tissue [Spandidos and Agnantis, Anticancer Res. 4: 269-272, 1984]. Our results revealed a significant elevation of Ha-ras transcripts in malignant compared to normal tissue. In the present follow-up study we have examined the relationship of Ha-ras oncogene expression to the various clinicopathological parameters of these tumors. Although elevated expression was observed in all breast tumors as compared to their respective normal breast tissue there was no correlation with the tumor stage as defined by the TNM system. However, several correlations between Ha-ras oncogene expression and histologic parameters were found and comparisons of the mean value of Ha-ras oncogene expression with the parameters examined showed the following: the stellate tumor margin and the larger tumor size had the lowest mean value; the infiltrating duct histologic type had the highest mean value; the mean value was lower in the presence of lymphocytic infiltration in the tumor; a higher mean value was obtained in cases with lymph node metastases.

Breast Neoplasms↗

PubMed1986

[Is prolonged psychological stress an etiological factor in breast cancer?].

1,088 women with cancer were seen in a period of 4 1/2 years at the Cancer Centre of the Greek Social Security Department in Athens. The authors present their results as far as psychological stress influences the development of cancer of the breast in 813 patients (Group A) and in 685 women who did not have cancer of the breast (Group B). They were able to show that Group A had a positive correlation which was statistically very significant (p less than 0.001) with the following parameters: the death of a much-loved person; the negative behaviour of the husband; an unexpected change in life style; continual conflicts in the family; financial problems; unsatisfactory sex life; consultations with a psychiatrist and allergy. There was a positive correlation which was statistically significant (p less than 0.01) with the parameters: disappointment in sentiment; a lowering in life style; a family history of cancer of the breast; hypertension; late start in the menarche and the onset of the menopause. The authors conclude that they believe that it is useful to look at all the factors that are known as risks for cancer of the breast, including the influence of psycho-traumatic factors.

Adult↗

PubMed1984

The reliability of frozen-section diagnosis in various breast lesions: a study based on 3451 biopsies.

In this study, we analyze breast biopsy material over a 5-year period and we compare the results of frozen-section diagnosis with the corresponding diagnosis of the permanent histologic sections. In this study, which represents the largest series in the available international literature, it is proven that frozen-section diagnosis of various breast lesions is a highly accurate procedure in spite of the difficulties facing the pathologist with the frequent borderline or premalignant lesions. The great responsibility of the pathologist is emphasized.

Biopsy↗

PubMedDate not supplied

Contribution of exfoliative cytology to the diagnosis of laryngeal lesions.

OBJECTIVE: To estimate the diagnostic accuracy and reliability of exfoliative laryngeal cytology. STUDY DESIGN: Over three years (1996-1999) cytologic smears were obtained from clinically suspicious laryngeal lesions during laryngoscopy in a total of 31 selected patients (28 males and 3 females with an age range from 28-90 years). The cytologic diagnoses were analyzed and correlated with the histologic and final clinical diagnoses in 17 and 14 cases, respectively. Cytologic identification of the exact histologic type of the lesion was evaluated in 17 patients from whom both cytologic smears and biopsy material were obtained. RESULTS: The overall specificity was 100%, with no false positive diagnoses. The overall sensitivity was 93.3%, with one false negative cytologic diagnosis, in a case of non-Hodgkin's lymphoma. Cytohistologic correlation showed complete agreement between cytologic and histologic diagnoses in five of six benign lesions, in four cases of dysplasia and in six cases of squamous cell carcinoma. The overall diagnostic accuracy of cytology was 96.7% CONCLUSION: Exfoliative cytology by the smear technique is a reliable and accurate method in clinically suspected laryngeal lesions. Moreover, exfoliative cytology may be applied as the only alternative diagnostic method, especially in elderly patients with coexistent cardiorespiratory problems, when biopsy is not advisable or indicated.

Adult↗

PubMedDate not supplied

Immunohistochemical study of extracellular matrix components in epiretinal membranes of vitreoproliferative retinopathy and proliferative diabetic retinopathy.

PURPOSE: The migration, proliferation, differentiation, and adhesion of cells and other cellular functions are influenced by the surrounding extracellular matrix in normal and wound healing conditions. The formation of epiretinal membranes, a wound healing process, is a serious complication of retinal diseases, the most important being proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). In the present study, the authors investigated the expression of various extracellular matrix components and in particular tenascin, fibronectin, laminin, collagen IV, and MMP-3 glycoprotein as well as the expression of glial fibrillary acidic protein in each type of epithelial membrane in order to elucidate the role of these molecules in the formation of these two types of membranes. METHODS: The authors performed immunohistochemistry in 14 PVR and 14 PDR membranes, using antibodies against the above mentioned extracellular matrix components. Tenascin and fibronectin were observed as major components in the extracellular matrix, while laminin and collagen type IV were detected as minor components in both types of membranes. A higher fibronectin expression in PVR compared with PDR membranes was found (p=0.0035). A positive relationship of its expression with the proliferative activity (p=0.15) and collagen type IV expression (p<0.0001) was also observed. RESULTS: Tenascin expression was positively correlated with glial fibrillary acidic protein positive cells in PDR membranes (p=0.04). Collagen type IV localized around vessels was observed with high levels in PDR membranes (p=0.0031). CONCLUSIONS: The results indicated that the extracellular matrix components seem to be involved in PVR and PDR, contributing to tissue remodeling and perhaps by different pathogenetic pathways, which could reflect different stages of development in these two types of membranes.

Antigens↗

PubMedDate not supplied

Cytogenetic and molecular abnormalities in astrocytic gliomas (Review).

In recent years, there have been great advances in our understanding of the genetic events and the molecular biology of human brain gliomas. Cytogenetic information has suggested that a pattern of non-random abnormalities involving numerical deviations such as the gain, partial deletion, or total loss of chromosomes as well as translocations and structural rearrangements of certain chromosome lesions are characteristic features for some tumors. In addition, the somatic activation of cellular oncogenes and inactivation of tumor suppressor genes represent important genetic alterations leading to progressive disorder of normal cellular growth control mechanisms. This review describes the abnormal chromosomal and molecular abnormalities that occur during formation of brain tumors of astrocytic origin, particularly fibrillary astrocytic neoplasms. The most frequent genetic alterations include inactivation of the p53, p16, Rb and PTEN genes, and overexpression of the CDK4, EGFR and VEGF genes. Other less well defined abnormalities include aberrations in chromosomes 1, 9, 10, 11, 19 and 22.

Astrocytoma↗

PubMedDate not supplied

Altered patterns of retinoblastoma gene product expression in benign, premalignant and malignant epithelium of the larynx: an immunohistochemical study including correlation with p53, bcl-2 and proliferating indices.

In order to study the altered Rb, bcl-2 and p53 proteins expression during laryngeal carcinogenesis and to elucidate the role of these molecules in the development and progression of the lesions, we have examined the immunohistochemical expression of these markers in a series of 41 squamous cell carcinomas, 14 cases of in situ carcinoma, 47 with epithelial dysplasia, 11 papillomas and 20 cases of keratosis. Rb protein was expressed in 69.7% (> 5% positive neoplastic cells) of squamous cell carcinomas and p53 in 40% (> 5% positive cells). There was a strong statistically significant difference for Rb, Ki-67 and PCNA immunostaining between malignant, premalignant and benign lesions, increasing from keratosis, papillomas, dysplasia to carcinoma in situ or infiltrating squamous Ca. Rb protein expression was also strongly correlated with p53, Ki-67 and PCNA, while p53 protein was strongly correlated with Ki-67 (p = 0023) and PCNA (p = 0.0031) indices, in all lesions. In conclusion Rb and p53 altered proteins expression seems to play an active role in laryngeal carcinogenesis, probably from the early phase, and is correlated with proliferative activity. Also, Rb protein expression is correlated with the progression of the lesion and could be considered as indication of poor prognosis in laryngeal lesions.

Adult↗

PubMedDate not supplied

Immunohistochemical localization of metallothionein in human breast cancer in comparison with cathepsin D, stromelysin-1, CD44, extracellular matrix components, P53, Rb, C-erbB-2, EGFR, steroid receptor content and proliferation.

Metallothionein (MT) is a low molecular weight, cysteine-rich, zinc-binding protein that may have a function in cellular repair processes, growth and differentiation. Using a monoclonal antibody (E9) to metallothionein, we investigated the immunohistochemical expression of MT in routinely fixed and paraffin-embedded tissue from 98 cases of female breast carcinomas. The MT expression was studied in comparison with the expression of the basement membrane (BM) antigens (type IV collagen, laminin), fibronectin, cathepsin D, adhesion molecule CD44, p53 protein, the pRb, c-erbB-2 oncoprotein, EGFR, stromelysin-1, proliferation indices (Ki-67, PCNA), steroid receptor content as well as with other conventional clinicopathological parameters of breast cancer. Strong MT expression was observed in the majority of tumour cells in 18.4% of tumours, focal MT positivity in 13.3% and almost complete lack of MT expression in 68.4% of cases (mean value 33.36 +/- 26.36). The MT expression in carcinoma cells was strongly associated with the DCIS component of the tumour (p < 0.0001). High values of MT were correlated with low steroid receptor status (p = 0.08 for ER receptor and p = 0.019 for PgR receptor content). MT positive cases were correlated with stromelysin-1 expression (p = 0.059) and cathepsin D (p = 0.058). These findings suggest that MT expression is characteristic of the early phase of breast carcinogenesis, possibly regulated by hormones, and could be a new potential prognostic marker in breast cancer.

Adult↗

PubMedDate not supplied

Immunohistochemical evaluation of cathepsin D expression in colorectal tumours: a correlation with extracellular matrix components, p53, pRb, bcl-2, c-erbB-2, EGFR and proliferation indices.

The immunohistochemical Cathepsin D (CD) expression of tumour and stromal cells was investigated in a series of 93 human colorectal adenocarcinomas and 22 adenomas with the intention to evaluate its prognostic significance and its contribution in the metastatic potential of colorectal cancer. CD expression was correlated with the expression of extracellular matrix components (collagen type IV, laminin and fibronectin), p53 protein, pRb, bcl-2, c-erbB-2, EGFR, proliferation indices (Ki-67, PCNA) as well as with other conventional clinicopathological features. CD expression (> 10% of positive tumour cells) was observed in 60.2% of carcinomas and in 72.7% of adenomas. Stromal CD expression was detected in all cases. A statistically significant positive correlation between neoplastic cells CD and stromal cells CD (SCCD) was observed in both carcinomas and adenomas. Cancer cells CD (CCCD) was positively correlated with collagen type IV and pRb expression as well as with PCNA score. In carcinomas, SCCD expression was statistically correlated with p53 protein and pRb expression and a trend for correlation with PCNA score was found. These data suggest that Cathepsin D of cancer and stromal cells, especially in combination with other markers, may provide more information about the biological behaviour of colorectal cancer.

Adenocarcinoma↗

PubMedDate not supplied

Spontaneous evolution of human papillomavirus infection in the uterine cervix.

BACKGROUND: Little is known about the natural history and the malignant potential of low-grade cervical intraepithelial neoplasia associated with human papillomavirus (HPV) infection. Cervical cancer remains the second most frequent cause of death in women across the world. Epidemiologic and molecular studies have shown that human papillomavirus (HPV) is associated with cervical carcinogenesis. In this prospective study we examined the behavior of low-grade cervical intraepithelial lesions associated with HPV infection over a 6-year period. MATERIAL AND METHODS: During 1992, women with Papanicolaou smears reporting koilocytotic atypia (HPV effect) with or without grade 1 cervical intraepithelial neoplasia (HPV +/- CINI, low grade squamous intraepithelial lesions, LgSIL), along with colposcopic impression of LgSIL were included to the study. Between 1992 and 1998 all women underwent repeat Papanicolaou smears, colposcopic evaluation and HPV DNA testing every six months. HPV typing of cervical scrapes was done by PCR. RESULTS: A total of 330 women completed at least 6 years of follow up. Among women with high-risk HPV types (16/18), the presence of dysplasia (grade 1 cervical intraepithelial neoplasia) was significantly correlated with the progression of the lesion; 29% of cases with HPV + CINI (15 out of 75) progressed to more severe lesions versus only 9% of cases with HPV infection (18 out of 225), P < 0.001, chi-square test. The incidence of histologically confirmed progressive lesions was significantly greater in women with mild dysplasia (18 out of 75, 24%) compared to women without dysplasia (13 out of 255, 5%), P < 0.001, chi-square test. CONCLUSIONS: In our study HPV typing was not predictive of the evolution of low-grade intraepithelial lesions associated with HPV infection. Standard cytologic screening and colposcopy are the most effective means of monitoring low-grade lesions.

Cervix Uteri↗

PubMedDate not supplied

Antiproliferative activity of interferon gamma in superficial bladder cancer.

BACKGROUND: Although the antiproliferative activity of interferon gamma has been reported in various tumours, this has not been studied in bladder cancer. Proliferative cell nuclear antigen and Ki67 growth fractions were estimated in this study in superficial bladder cancer, as a measure of the antiproliferative effect of interferon gamma. MATERIALS AND METHODS: Superficial bladder cancer samples before and after four weekly intravesical instillations of 0.7 mg IFN gamma were studied immunohistochemically for proliferative cell nuclear (PCNA) and Ki67 antigens in 25 evaluable patients. RESULTS: Ki67 growth fraction decreased from median 5% preoperatively to 1% postoperatively (p = 0.0015) and proliferating cell nuclear antigen from 20% to 5% respectively (p = 0.0001). Net reductions of both indices after the interferon instillations were significantly higher in T1 than in Ta tumours (p = 0.0431 for Ki67, and p = 0.0350 for PCNA). CONCLUSIONS: The intravesical instillations of the present dose of interferon gamma have a significant cytostatic effect on superficial bladder cancer cells as this is evidenced by the significant decrease of the growth fractions measured by means of the proliferating cell nuclear and the Ki67 antigens.

Antineoplastic Agents↗

PubMedDate not supplied

Cytogenetic and molecular genetic abnormalities in primitive neuroectodermal tumors of the central nervous system.

Primitive neuroectodermal tumors constitute a large class of pediatric brain tumors. Despite notable recent advances in improving treatment and survival, the pathogenesis and the molecular genetic bases of these malignancies remain poorly understood. Combined cytogenetic and molecular genetic approaches have been used to identify genomic alterations in different histologic tumor types. Translation of these advances from basic science to clinical application is currently underway. Goals for the future include the development of more efficacious treatment strategies while simultaneously lessening toxicity. The most important cytogenetic and molecular genetic abnormalities documented to date together with their potential prognostic significance are reviewed.

Aneuploidy↗

PubMedDate not supplied

Prognostic significance of p53 in the cancer of the larynx.

p53 is a nuclear phosphoprotein acting as a transcription factor to regulate cell cycle progression and apoptosis, mediated by a number of target genes. p53 mutant proteins have lost a) the ability to act as sequence-specific transcription factors and b) their tumour suppressive properties. As p53 is the most commonly mutated gene in human cancer, including laryngeal squamous cell carcinoma, an aggressive and most frequent tumour of head and neck, it has attracted a great deal of interest as a prognostic factor, diagnostic tool and therapeutic target. This article reviews the current understanding of the prognostic significance of p53 in laryngeal squamous cell carcinoma. Immunohistochemical staining techniques and molecular genetics demonstrated that p53 activation is an early event in laryngeal squamous cell carcinogenesis but can not be used as a reliable prognostic marker.

Genes, p53↗

PubMedDate not supplied

Immunohistochemical expression of Bcl-2 protein in breast lesions: correlation with Bax, p53, Rb, C-erbB-2, EGFR and proliferation indices.

Expression of bcl-2 protein was investigated and correlated with Bax, p53 and Rb proteins, c-erbB-2, EGFR and the proliferation indices PCNA, Ki-67 and MIB1 as well as with the conventional clinicopathological parameters in 95 cases for breast cancer tissue and 20 cases of benign hyperplastic lesions. Bcl-2 and Bax proteins immunoreactivity was detected in normal, hyperplastic and neoplastic breast epithelium. Expression of the bcl-2 protein was detected in 40% of carcinomas (> 10% positive neoplastic cells) and 85.2% of the benign hyperplastic lesions. Bax protein expression was detected in 8.1% of the carcinomas and 5.3% in the hyperplastic group. Rb and p53 proteins were detected in 75.5% and 45.5% of carcinomas. No relationship was observed between bcl-2 expression and patient's age, tumour size, tumour type and grade, lymph node status, Rb protein expression and proliferation indices. However, a strong positive relationship was detected between bcl-2 and Bax (p = 0.008), estrogen (ER) (p = 0.007) and progesterone receptors' (PgR) status (p = 0.0003). An inverse correlation with p53 protein (p = 0.004) was detected. Furthermore, a strong correlation was also observed between pRb and p53 (p = 0.001). The results indicate that in breast cancer bcl-2 protein expression may be under hormonal control. Since the expression is bcl-2 protein was inversely correlated with p53 protein expression, we suggest that bcl-2 may be related with favourable outcome in breast cancer.

Breast↗

PubMedDate not supplied

Immunohistochemical expression of the p53, p21/Waf-1, Rb, p16 and Ki67 proteins in multiple myeloma.

The aim of this study was to investigate the immunohistochemical expression of the proteins p53, Waf-l/p21, Rb, p16 and Ki67 in 38 cases of multiple myelomas (MM) and 4 cases of solitary extramedullary plasmacytomas in relation to the tumor histological grade and stage. In bone marrow (BM) biopsies from MM, overexpression of p53 and p21 proteins, in comparison to plasma cell infiltrates in non-pathological bone marrow, was detected in 13 out of 38 and 21 out of 38 cases, respectively. The combined immunoexpression of p53 and p21 proteins in the 38 cases of MM showed the following patterns: a) p53+/p21+ (13 cases) b) p53-/p21+ (8 cases) and c) p53-/p21- (17 cases). Rb, p16 and Ki67 proteins were detected in tumor cells in all 38 cases and their expression increased proportionally to tumor grade. The 4 cases of solitary extramedullary plasmacytomas showed the p53+/p21+ pattern in 2 cases and the p53-/p21+ pattern in 2 cases, all of them displaying Rb, p16 and Ki67 expression in tumor cells. The pattern p53+/p21+ might represent cases with wild-type p53 able to induce p21 expression. However, in previous studies p53 mutations were reported in about 3-10% of MM, and they were strongly associated with advanced disease. Thus, in some p53+/p21+ cases associated with high p53 expression and advanced disease, p53 gene cannot be excluded and up-regulation of p21 expression may be p53- independent. P53 overexpression correlated with increased tumor grade (p < 0.005), advanced histological stage (p < 0.001) and Ki67 expression in more than 10% of tumor cells (p < 0.001). Since increase in Ki67 expression also correlated with increased tumor grade (p < 0.001) and advanced histological stage (p < 0.001), these findings suggest that impairment of the p53 growth control pathway is associated with tumor progression in MM. Thus, p53 and Ki67 immunostaining in routine BM biopsies may be helpful for the detection of MM with potentially aggressive behavior. Overexpression of p21 in MM correlated with higher Ki67 expression (p < 0.005), suggesting that the p21 function of arresting cell-cycle is impaired. Ki-67 expression in MM increased in parallel with p16 (p < 0.001) and Rb expression (p < 0.001). Rb expression could represent a growth control response which, however, might not be able to induce growth arrest in view of the parallel increase in Ki67 expression and of previous findings showing that Rb protein in MM cells is expressed mostly in its phosphorylated form.

Cyclin-Dependent Kinase Inhibitor p16↗

PubMedDate not supplied

Tumor markers in stage P1 bladder cancer.

BACKGROUND: The infiltration of muscularis mucosa in superficial bladder cancer has been reported to be predictive of an unfavourable course of the disease. MATERIALS AND METHODS: We studied immunohistochemically Ki-67, PCNA and p53 tumour markers in 68 P1a and Pib bladder tumours. RESULTS: A statistically significant difference (p = 0.01) was found in the distribution of grades between stages P1a and P1b, with more grade 3 and less grade 2 tumours in the latter category. Univariate analysis revealed a strong association of Ki-67 (p = 0.001) and PCNA (p = 0.032) only with stage. P53 protein expression did not have any significant association with either stage or grade. In 60 patients entered into the multivariate analysis a clearly predominant, significant effect of stage on Ki-67 (p = 0.000) was shown. CONCLUSION: Increased proliferative activity when compared to P1a is present in P1b bladder tumours, as detected by the increased expression of Ki-67 proliferating antigen. The immunohistochemical study of Ki-67 antigen may help in predicting stage P1 tumours' behaviour, even in cases where pathological distinction of P1a and P1b substages is difficult.

Biomarkers, Tumor↗