Biomedical subjects

N Kavantzas

Publications and source records attributed to N Kavantzas.

At least 37 records · Page 2Linked to original sources

PubMed2001

Microscopical examination of the localisation patterns of two novel rhodamine derivatives in normal and neoplastic colonic mucosa.

Tissue characterisation by fluorescence imaging, using exogenous fluorophores, is a promising method for cancer detection. Histochemical alterations in the composition of mucins, when neoplastic transformations occur, could be exploited to derive more selective fluoroprobes indicative of early malignant transformation. The aim of this work was to develop and examine tumour selective fluoroprobes for colon cancer diagnosis, as well as to determine the morphological components where selective dye accumulation has occurred. Two novel fluoroprobes: rhodamine B-L-leucine amide and rhodamine B-phenylboronic acid were synthesised and examined together with Mayer's mucicarmine, alexa 350-wheat germ agglutinin (WGA) and tetramethyl rhodamine-concanavalin A (ConA). Fluorescence microscopy studies were performed with deparaffinised human colon sections, using an epifluorescence microscope equipped with a colour CCD camera. The intense accumulation of the novel fluoroprobes was localised in the amorphous material in the lumen of neoplastic crypts. To gain insight into the localisation patterns, mucicarmine, alexa 350-WGA and tetramethyl rhodamine-ConA were used. Alexa 350-WGA reacted primarily with mucin secreted in the malignant crypt lumen suggesting that this material is rich in sialic acid and N-acetylglucosaminyl residues. These derivatives clearly and consistently distinguished non-neoplastic from neoplastic human colon tissue sections. The intense accumulation at the altered mucins indicates that they could be used as fluoroprobes of biochemical alterations for carcinoma detection.

Carmine↗

PubMed2001

Morphometric microvascular characteristics predict prognosis in superficial and invasive bladder cancer.

Recent research has shown that neovascularization, quantitated by microvessel density (MVD), constitutes a strong prognostic indicator in patients with invasive urothelial carcinomas. These studies, however, have focused only on MVD as the only factor reflecting angiogenesis in transitional-cell carcinomas (TCCs). The objective of this report was to evaluate multiple morphometric microvascular characteristics besides MVD in superficial and muscle-invasive TCCs separately, to provide a better approach to the relationship between angiogenesis, clinicopathological parameters, and prognosis. Histologic sections from 115 TCCs [35 superficial (T1) and 80 muscle-invasive] were immunostained for CD31 and evaluated using image analysis for the quantitation of MVD, area, total vascular area, major axis length, minor axis length, perimeter, compactness, shape factor, and Feret diameter. Patients were followed-up until death (n=31) or for an average of 42.2 months (median 38.5 months). MVD increased with progressing T category (P=0.049) but area (P=0.033), major axis length (P=0.022), perimeter (P=0.043), and Feret diameter (P=0.042) were highest in T2 tumors. Area was the single independent predictor of adverse significance in T1 TCCs, whereas for muscle-invasive tumors, survival was independently predicted by MVD. Regarding disease-free survival in superficial tumors, the single significant independent parameter was compactness, whereas area was an independent favorable indicator of disease-free survival for patients with invasive TCCs. It is concluded that the prognostic significance of neovascularization is better assessed by area and shape-related morphometric characteristics, whereas MVD becomes influential only with regard to overall survival of patients with invasive tumors.

Adult↗

PubMed2001

Prognostic evaluation of the microvascular network in myelodysplastic syndromes.

Considering the recently stated suggestion of neovascularization being implicated in myelodysplastic syndromes (MDS) pathogenesis, we evaluated multiple morphometric microvascular characteristics in MDS, in relation to clinicopathologic factors and prognosis. Trephines from 50 newly diagnosed MDS patients were immunostained for factor VIII and compared to those from 20 controls, 10 chronic myelomonocytic leukemia (CMML) and 12 acute myeloid leukemia (AML) patients. Quantitation of microvessel density (MVD), area, total vascular area (TVA), major and minor axis length, perimeter, compactness, shape factor, Feret diameter, and the number of branching vessels was performed by image analysis. Overall, the MDS group had significantly higher MVD, TVA, minor axis and shape factor values and significantly lower compactness than the control group. AML was characterized by increased vascularity compared to MDS and CMML, as well as by the presence of flattened microvessels (lower values of shape factor). Hypercellular MDS showed higher MVD. RA/RARS displayed larger caliber vessels than RAEB, which explains the favorable prognostic effect of increased size-related parameters on progression and/or survival. Moreover, decreased compactness and MVD were independent predictors of longer progression-free survival. It is concluded that angiogenesis is involved in the conversion of normal marrow to MDS and ultimately to AML and that disease progression within MDS is accompanied by qualitative alterations of the microvascular network. Furthermore, size-related parameters affect survival, while shape-related parameters and MVD are more influential with regard to progression-free survival.

Acute Disease↗

PubMed2001

DNA topoisomerase IIalpha expression correlates with cell proliferation but not with recurrence in intracranial meningiomas.

AIMS: To assess the value of topoisomerase IIalpha (TopoIIalpha) as a novel proliferation-associated molecule, by correlating its immunohistochemical expression with Ki67 (MIB-1), cell proliferating cell nuclear antigen (PCNA) and mitotic index in meningiomas. Furthermore, to investigate its relation to standard clinicopathological parameters and patients' outcome. METHODS AND RESULTS: This retrospective study comprised a consecutive series of 57 patients with primary intracranial benign and atypical meningiomas. Six tumours recurred (10.5%) following complete surgical resection, within a follow-up period ranging from 21 to 108 months (median 60 months). Archival formalin-fixed paraffin-embedded sections were stained with standard immunohistochemical methods. The lower proliferation indices were obtained with TopoIIalpha and the higher ones with PCNA. TopoIIalpha labelling index (LI) ranged from 0.1% to 10% (median 0.5%) and, along with Ki67 and PCNA LI, increased with malignancy grade (P=0.049, P=0.045 and P < 0.001, respectively), displaying though a significant overlapping between grades. A significant positive correlation was shown between TopoIIalpha and Ki67 (P < 0.001) or PCNA (P=0.032). In univariate and multivariate survival analysis, TopoIIalpha failed to predict meningioma recurrence and did not affect disease-free survival. Only tumour size and Ki67 LI provided significant prognostic information in this regard. CONCLUSIONS: TopoIIalpha expression may be useful as a novel proliferation marker in meningiomas, presenting several advantages over the markers currently in use, notably providing a better estimate of the number of cycling cells and a more uniform nuclear staining pattern. However, it fails to discriminate between benign and atypical neoplasms and does not provide prognostic information beyond that obtained by Ki67.

Antigens, Neoplasm↗

PubMed2001

Signet ring basal cell carcinoma. A case study emphasizing the differential diagnosis of neoplasms with signet ring cell formation.

Signet ring cells are cells in which the nucleus is crescentically compressed to the cellular border so that the cells look like signet rings. Due to the pluripotential nature of the basal cells of the epidermis, basal cell carcinoma displays many histopathological variants. We herein report the rare case of a middle-aged woman who had a basal cell carcinoma on the skin of the upper lip. The neoplasm was predominantly composed of cells with signet ring configuration. Histochemically, the latter were mucin-negative. Immunohistochemistry demonstrated intracytoplasmic reactivity for cytokeratin MNF116 with strong staining intensity, as well as for smooth muscle actin. The signet ring tumor cells were S100 protein-negative and carcinoembryonic antigen-negative. The lack of ploidy abnormality as well as of molecular alterations in K-ras and p53 genes may explain in part the non-aggressive biological behavior of the present tumor. Because of potential diagnostic difficulties, the pathologist should be aware of this unusual form of basal cell carcinoma. A brief review of the literature on the differential diagnosis of signet ring cell cutaneous tumors is presented.

Adenocarcinoma↗

PubMed2001

Correlations between nuclear/cytoplasmic area ratio and classification of cervical smears.

The aim of this study was to assess the nuclear/cytoplasmic (N/C) ratio using computerized image analysis of cervical smears with intraepithelial neoplasia (CIN) grade I to III associated or not with cellular changes of human papillomavirus (HPV) in an attempt to determine if this method is more sensitive for the estimation of the grade of CIN. One hundred and ten cervical smears from women with a mean age 35.03 years were studied. The cytological diagnosis was as follows: CIN I + HPV (11), CIN II + HPV (11), CIN II + HPV (8), CIN I (7), CIN II (6), CIN III (8), Ca (22), HPV (32), CIN I-II + HPV (2) and CIN II-III + HPV (3). All cases were histologically examined: 93 cases were in agreement and 17 were under- or overestimated cytologically. The morphometric study of cervical smears was carried out by image analysis. Data were analysed by one way analysis of variance followed by Bonferroni test of multiple comparisons. Statistically significant differences were detected between the three grades of CIN or CIN HPV or only HPV (p<0.0001). The results demonstrated that the N/C ratio measured by image analysis on precancerous lesions of cervical smears could be considered as an additional tool for the classification of cervical smears, especially in determining the discrepancies between cytological and histological diagnoses.

Adolescent↗

PubMed2001

Nuclear/Nucleolar morphometry and DNA image cytometry as a combined diagnostic tool in pathology of prostatic carcinoma.

Paraffin tissue sections from 50 patients with prostate adenocarcinoma were used to study nuclear and nucleolar morphometric features by image analysis. The results were compared to DNA ploidy and Gleason grade. In the examined histological samples nuclear and nucleolar areas were positively interrelated. It was also noticed that the higher the percentage of nucleolated nuclei, the bigger the nuclear and nucleolar areas. The morphometric characteristics did not differ significantly among the four grades of the examined specimens. In well-differentiated carcinomas the DNA index was lower than in the rest at a statistically significant level. Hypodiploid carcinomas were found to possess significantly bigger nuclear areas than any other DNA index group. Morphonuclear evidence of anaplasia and DNA aneuploidy may be used as diagnostic tools in prostate cancer in addition to Gleason grade.

Adenocarcinoma↗

PubMed2000

Membranous glomerulonephritis: a morphometric study.

Archival material from 45 renal biopsies with a diagnosis of idiopathic membranous glomerulonephritis (MGN) were studied by computer-aided image analysis in order to evaluate the prognostic significance of glomerular and interstitial morphometry in MGN. The control group consisted of thirty seven normal renal biopsy specimens. The surface area, the perimeter, the major axis length and the shape factor of renal glomeruli as well as the percentage of the interstitial fibrosis were measured. All the morphometric parameters related to the size of glomeruli had significantly higher values in the patient group (p = 0.000 for all the parameters). However, no significant difference of the glomerular size between different stages of MGN was observed. In contrast, the percentage of interstitial fibrosis increased as the MGN stage rose (median values: 10.3% in stage 1, 14.2% in stage II, 26.9% in stage III, 28.9% in stage IV and 34.2% in stage V, Kruskal-Wallis ANOVA H = 37.645, p = 0.000). In the multivariate analysis the percentage of interstitial fibrosis was the only independent prognostic factor (p = 0.013). Our findings suggest that, in membraneous glomerulonephritis, the interstitial fibrosis increases as the MGN stage progresses, while the size of renal glomeruli has increased at a very early stage of the disease. This fact may indicate that interstitial fibrosis, not glomerular lesions, is mainly responsible for the reduction of renal function.

Adult↗

PubMed2000

Correlation of tumor markers p53, bcl-2 and cathepsin-D with clinicopathologic features and disease-free survival in laryngeal squamous cell carcinoma.

Various recognized prognostic factors in squamous cell carcinoma (SCC) of the larynx influence the therapeutic options offered to an individual patient in order to extend the survival expectancy. Additional prognostic indicators are required in specific patient subgroups. The present study used a standard immunohistochemical technique in order to retrospectively evaluate the accumulation of p53 gene product and the immunoreactivity of bcl-2 protein and cathepsin-D as possible prognostic markers of laryngeal SCC. Formalin-fixed, paraffin-embedded tumor materials were obtained from a series of 64 patients with cancer of the larynx. Immunostaining was evaluated by computerized image analysis. The accumulation of p53 protein was found in 57.8% (37/64) of the patients and was associated with large tumor size. The percentage of p53-positive neoplastic cells increased in high-grade carcinomas, particularly when they simultaneously demonstrated cathepsin-D immunoreaction in stromal cells (P = 0.049); bcl-2 immunoexpression was found to be generally limited. Cathepsin-D immunostaining was observed in tumor parenchymal and stromal cells (31.25% and 37.5% of all cases, respectively); it was found to be useful in defining patient subgroups with differences in relapse-free survival. Among patients with posi-tive lymph nodes, those with cathepsin-D immunopositive tumor cells were at higher risk for relapsing (P = 0.0395). Although the classical prognostic factors of laryngeal carcinoma retain their predominance, cathepsin-D immunoreactivity may serve as an additional prognosticator in specific patient subgroups.

Adult↗

PubMed2000

Immunodetection of gastrin-releasing peptide in malignant melanoma cells.

Gastrin-releasing peptide (GRP), the mammalian counterpart of bombesin, was first identified in the nervous system of the gastrointestinal tract. Little is known about its distribution in the human skin or about its function in certain diseases such as malignant melanoma. Recently functional GRP receptors have been found on human melanoma cell lines. We therefore investigated, using immunohistochemistry, whether human melanoma cells express GRP and whether there is a significant change in its distribution among the different clinical types of melanoma and a connection to histopathological features such as growth phase, type of malignant cells, Breslow thickness and Clark level of invasion. We demonstrated the existence of GRP in all clinicopathological types of melanoma; a predilection for quantitatively increased GRP immunostaining was noticed in nodular melanomas (P = 0.007). As well as this, we observed a restriction of GRP expression at a specific level of invasion, i.e. within the reticular dermis (Clark IV) (P = 0.032). GRP immunoreactivity was found to be associated with an increased amount of melanin pigment in malignant cells (P = 0.054). The presence of GRP in malignant melanocytes, along with its association with the various histopathological features, suggests that GRP may play a role in the pathophysiology of this type of cutaneous tumour.

Gastrin-Releasing Peptide↗

PubMed2000

Significance of nuclear morphometry as a diagnostic tool in fine-needle aspirates of the liver.

OBJECTIVE: Classification of hepatic tumours and tumour-like conditions can sometimes be difficult to establish by light microscopy. Our aim was to determine the value of computerized interactive nuclear morphometry in the preoperative prediction of primary or metastatic malignancy as opposed to non-malignant lesions, in fine-needle aspirates (FNA) of hepatic lesions. METHODS: Alcohol-fixed, Papanicolaou-stained FNA smears of 99 histologically proven hepatocellular carcinomas (HCCs), metastatic neoplasms and benign lesions were measured by computerized image analysis with regard to nuclear major axis, minor axis, perimeter, area, shape factor and hyperchromasia. Data were coded, entered into a computerized database, and statistically analysed with SPSS programs. RESULTS: Tukey HSD test for multiple comparisons, assessed for all features except hyperchromasia, showed that the mean values of morphometric features of nonmalignant cells were significantly different from those of malignant cells, either primary or metastatic, whereas differences between morphometric characteristics of HCCs and metastatic neoplasms were insignificant. Kruskal-Wallis analysis of variance revealed that hyperchromasia varied among the three groups of samples proportionally to the other nuclear features. The mean differences of all evaluated nuclear variables except minor axis were significant between grades II & III and grade IV HCCs. Morphometric mean values of well-differentiated HCCs differed significantly in comparison with those of non-malignant lesions; however, some degree of overlap was observed in the ranges of minor axis and hyperchromasia mean values. CONCLUSIONS: The three most important cytological criteria of nuclear malignancy (hyperchromasia, enlargement and anisonucleosis), when quantified by morphometry, may be helpful in the differential diagnosis between non-cancerous liver lesions and HCCs (even those of high differentiation), since all the morphometric data showed pronounced differences between malignant and benign groups. Morphometry may also be used as a complementary tool in the cytological grading of HCCs.

Adult↗

PubMed2000

Computerized morphometric study on fine needle aspirates of cellular follicular lesions of the thyroid.

OBJECTIVE: To investigate the value of computerized nuclear morphometry in the differential diagnosis of cellular follicular lesions of the thyroid cytologically diagnosed on fine needle aspiration (FNA) smears. STUDY DESIGN: Sixty cases of FNA thyroid smears were cytologically diagnosed and classified as follows: 30 cases of follicular carcinoma, 20 cases of cellular hyperplastic nodules and 10 cases of follicular adenoma. Using an image analysis system, two morphometric variables, nuclear area and major axis length of the nucleus, were measured for each case. RESULTS: For both nuclear morphometric variables, statistical differences were found between carcinomas and hyperplastic nodules as well as between carcinomas and adenomas. No statistical differences were found between the nuclear variables in either hyperplastic nodules or adenomas. CONCLUSION: The results confirm the aim of our study, to establish nuclear morphometry by computerized image analysis as an additional tool in the differential diagnosis of thyroid follicular lesions cytologically diagnosed on FNA smears.

Adenocarcinoma, Follicular↗

PubMed2000

The nuclear morphometry by image analysis in the histopathologic diagnosis of lung cancer.

Classification of small cell lung cancer and non small cell lung cancer can sometimes be difficult to establish by light microscopy. Our aim was to determine the value of computerised interactive nuclear morphometry in the diagnosis of small cell lung cancer of intermediate type and non small cell lung cancer in thirty-nine histologic specimens. Histologic sections were measured by Sigma Scan software package with regard to nuclear big axis, small axis, perimeter, area and shape factor. Statistical analysis showed that nuclear minor axis values, at least, showed pronounced differences between small cell lung carcinomas of the intermediate type and non small cell lung carcinomas. So, the latter nuclear parameter may be used as a complementary tool in the histopathologic differential diagnosis of lung cancer.

Adenocarcinoma↗

PubMed1999

Chronic pneumonitis of infancy. An autopsy study of 12 cases.

The authors report 12 cases of chronic pneumonitis of infancy (CPI) studied retrospectively, on autopsy specimens. CPI is a new form of interstitial pneumonia, occurring exclusively is young infants and first described in 1995. Histologically, CPI is characterized by diffuse thickening with hypercellularity of the alveolar septa, associated with hyperplasia of type 2 pneumocytes and accumulation of intra-alveolar macrophages. In all children, initially in good health, the respiratory symptoms initially appeared at the age of 1 to 9 months, with a fatal course despite treatment. Many deaths of young infants, previously attributed to other types of interstitial pneumonia or unknown aetiology, could possibly be due to CPI.

Autopsy↗

PubMed1999

Renal leiomyosarcoma: report of three cases and review of the literature.

In the present study three cases of renal leiomyosarcoma are presented. All the patients were complaint about pain at right or left lumbar area and microscopic or gross haematuria. The clinical examination did not confirm any pathologic finding. The ultrasonographic and CT scan investigation of the patients revealed a renal mass. Under the frozen section diagnosis of malignant tumor in two cases and the cytological diagnosis of renal cell carcinoma in the third case, a radical nephrectomy was performed. In all the cases the pathological diagnosis was renal leiomyosarcoma. Because of the rarity of this neoplasm, the literature is reviewed, presenting the symptoms, the radiological findings, the diagnostic criteria and the differential diagnosis of the tumor. Radical nephrectomy remains the treatment of choice for this tumor, which exhibits an aggressive biological behavior and an unfavorable prognosis.

Aged↗

PubMed1998

A morphometric study of neovascularization in colorectal carcinoma.

BACKGROUND: Neovascularization reportedly is correlated with metastasis, recurrence, and prognosis in some types of tumors. Microvessel quantification in so-called "hot spots" has been studied extensively as the only factor reflecting angiogenesis in various malignant tumors. The objective of this report was to evaluate multiple morphometric microvascular characteristics in addition to microvessel density (MVD) in colorectal carcinomas to provide a better approach to examining the relation between angiogenesis and clinicopathologic factors and prognosis. METHODS: Histologic sections from 106 colorectal adenocarcinomas and 17 adenomas, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, total vascular area (TVA), and microvascular branching, as well as several morphometric parameters related to the vessel size or shape. RESULTS: MVD gradually decreased with progressing Dukes stage. The vascular branching counts were significantly higher in carcinomas than in adenomas, and remained unaffected through progressing Dukes stages. Shape-related parameters showed significant differences between carcinomas and adenomas and between different grades of differentiation. Branching counts and TVA were the only factors found to be of prognostic significance. CONCLUSIONS: This study provides evidence that neovascularization is an early critical event in colorectal tumorigenesis, reaching a maximum level early in the malignant process. Its prognostic significance is better assessed by quantification of TVA and the branching pattern of microvessels, whereas MVD does not provide significant prognostic information for colorectal carcinoma patients.

Adenocarcinoma↗

PubMed1998

Neuroendocrine differentiation in follicle-cell thyroid carcinoma: correlation to prognostic factors in papillary carcinoma.

The presence of NE-differentiation in the follicle-cell thyroid carcinoma has been investigated by immunohistochemical detection of chromogranin A in the neoplastic cells. It has been found that NE-differentiation was present in a significant percentage in the papillary Ca alone (46.60%) whereas all Huerthle-cell neoplasms and the large majority of follicular and undifferentiated carcinomas showed non reactivity for Chromogranin A. Moreover, we have correlated the presence of NE-differentiation to well known prognostic factors in papillary Ca. We found a statistically significant correlation between the neuroendocrine differentiation and some unfavourable factors such as old age of the patient, size of the tumor, invasion of thyroid capsule and lymphnode involvement. We suggested that NE-differentiation could be considered as an index of poor prognosis.

Adenocarcinoma, Follicular↗

PubMed1997

Computerized determination of proliferating cell nuclear antigen expression in meningiomas. A comparison with non-automated method.

Proliferating cell nuclear antigen (PCNA) expression has been proven to be a significant marker of cell proliferation in meningiomas, which correlates with growth rate and, as shown by several authors, possibly provides prognostic information concerning biologic behavior. However, the current method for determining PCNA labeling index (LI) is tedious and time consuming like all the nonautomated methods for evaluating cell kinetics, presenting high interobserver and interlaboratory variability and low reproducibility. In the present study, we introduce a semi-automated computer-assisted image analysis method for determining PCNA LI in 38 meningiomas, in parallel with the current nonautomated method. Image analysis technique permits unbiased cell counting, standardizes the degree of staining intensity and provides instant results. By calculating coefficient of variability, the method proved to be highly reproducible. The correlation between the results provided by the nonautomated and the semiautomated image analysis method showed a high agreement between them, with a correlation coefficient, r, of 0.82. In conclusion, we consider that image analysis contributes to the accuracy, reproducibility, and practicality of PCNA LI determination so that along with other useful parameters this significant marker may serve to predict the clinical behavior in meningiomas.

Histological Techniques↗