Biomedical subjects

N Kavantzas

Publications and source records attributed to N Kavantzas.

At least 19 recordsLinked to original sources

PubMed2003

Prognostic predictors of gastrointestinal stromal tumors: a multi-institutional analysis of 102 patients with definition of a prognostic index.

AIMS: The aim of this study is to identify prognostic factors influencing survival in patients with gastrointestinal stromal tumors (GISTs) and to identify a mathematical model that can predict lifetime expectation. METHODS: One hundred and two patients with GISTs, were followed retrospectively for a median period of 32 months (from 1 to 82 months). Complete follow-up data were available in 72 cases. All tumors were surgically resected and examined by conventional light microscopy, immunohistochemistry and image analysis. The tumors' location, size, histologic characteristics, immunophenotype, proliferative activity index (assessed by proliferating cell nuclear antigen (PCNA) and Ki-67 immunoreactivity) and the apoptotic markers bcl-2 and bax, were considered as potential prognostic factors and were correlated with patient survival. RESULTS: Tumor size >8 cm (p<0.03), presence of necrosis (p<0.02), number of mitoses >5/10 HPF (p<0.01), metastasis (p<0.001), and PCNA index >10% (p<0.004) were significant predictors of poor survival. Bcl-2 protein (p<0.0007) was a favorable prognostic indicator. If all tumors were treated as of uncertain malignant potential, the following mathematic model named GISTs Prognostic Index (GPI), could be formed by the linear regression technique: GPI exp=(49.6 months-Status of metastasis x 22.9185-Size in cm x 0.6801+bcl-2 expression% x 0.2569) (r(2)=0.67) (Prob>F=0.0001). CONCLUSIONS: Tumors' size, necrosis, mitoses, metastasis and PCNA index are independent poor prognosticators, while bcl-2 protein is associated with favorable prognosis. An interesting equation for survival in patient with GISTs has been reported.

Adult↗

PubMed2003

Clinicopathologic correlations of bone marrow angiogenesis in chronic myeloid leukemia: a morphometric study.

Various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemical staining, were evaluated in the bone marrow of 52 patients with chronic myeloid leukemia (CML) in chronic phase, in relation to several clinicopathologic parameters. Twenty control bone marrows and 15 cases of CML in blastic phase were also studied. Microvessel density (MVD), total vascular area (TVA) and several size- and shape-related parameters were quantitated in the region of most intense vascularization using image analysis. Overall, the group of chronic phase CML had higher MVD and size-related parameters and more branching microvessels than controls. Blastic phase was characterized by increased numbers of microvessels with a rounder shape and smaller caliber than chronic phase. A positive correlation emerged between marrow fibrosis and MVD as well as between white blood cell counts and rounder vessel sections. No relationship existed between microvascular parameters and Hasford or Sokal prognostic scores. In univariate analysis, overall and progression-free survival were adversely affected by MVD, size-related parameters, increased platelet count, age and spleen size. Multivariate analysis indicated that microvessel area was related to progression-free survival, whereas both MVD and area were significant prognosticators of overall survival, even when Hasford or Sokal scores are introduced into the model. Our data suggest that changes in angiogenic parameters may participate in the conversion of normal marrow to CML and ultimately to blastic transformation. More importantly, MVD and microvessel caliber are significant predictors of patient survival and progression.

Adolescent↗

PubMed2003

Mitosin, a novel marker of cell proliferation and early recurrence in intracranial meningiomas.

The expression of mitosin, a novel proliferation-associated molecule was evaluated immunohistochemically in a consecutive series of 47 patients with primary intracranial benign and atypical meningiomas. Mitosin expression was correlated with proliferation markers Ki-67 (MIB-1), proliferating cell nuclear antigen (PCNA), topoisomerase IIalpha (TopoIIalpha) and mitotic index, as well as with standard clinicopathological parameters and patient outcome. Seven tumors recurred (14.8%) following gross total resection, within a follow-up period ranging from 21 to 108 months (median 60 months). The higher proliferation indices were obtained with mitosin and PCNA and the lower ones with TopoIIalpha. Mitosin labeling index (LI) ranged from 0.1 to 57% (median 3%), with a significant overlapping of values between grades. A significant positive correlation was shown between mitosin LI on the one hand and Ki-67 LI (p < 0.001), or the mitotic index (p = 0.027) on the other. The incidence of recurrence was higher in cases with a mitosin LI higher than 3% (p = 0.048). Univariate analysis disclosed mitosin LI (p = 0.033) along with the mitotic index (p = 0.024) and tumor size (p = 0.028) as significant predictors of shortened recurrence-free survival. In multivariate analysis, the labeling indices of mitosin (p = 0.035) and Ki-67 (p = 0.032), along with tumor size, were shown to provide independent prognostic information, beyond that obtained by standard clinical and pathological parameters. However, as indicated by factor analysis, the prognostic information yielded by mitosin was superior to that provided by the remaining proliferation markers (p = 0.041). We conclude that mitosin immunohistochemical expression, although failing to discriminate between benign and atypical meningiomas, may be of use as a novel cell proliferation marker and as a predictor of tumor recurrence.

Antigens, Neoplasm↗

PubMed2003

Immunohistochemical detection of cell cycle regulators, Fhit protein and apoptotic cells in parathyroid lesions.

OBJECTIVE: The pathological distinction between parathyroid neoplasms and hyperplasias remains difficult. Changes in cell cycle control may lead to clonal proliferation and precede tumorigenesis. The parathyroid adenoma 1 oncogene, subsequently identified as the gene encoding cyclin D1, has been shown to be important to parathyroid tumour development. In addition to cell proliferation, the mechanisms of parathyroid cell turnover include apoptosis. The tumour-suppressor activity of the fragile histidine triad gene (FHIT) is linked to its proapoptotic function and cell cycle control. We attempted to evaluate the cellular proliferative kinetics and apoptotic function of the parathyroid glands in patients with non-familial hyperparathyroidism (HPT). DESIGN: TIssue specimens were taken from 40 patients with primary HPT (17 adenomas, two carcinomas and 21 primary hyperplasias) and from 30 patients with secondary HPT. Normal glands served as controls. METHODS: In a standard immunohistochemical procedure, monoclonal antibodies to Ki-67 antigen and single-stranded DNA were applied to detect cycling and apoptotic cells respectively; polyclonal antibodies to cyclin D1 and Fhit protein were used. Immunostaining was estimated by image analysis and statistical analysis was subsequently performed. RESULTS: Significantly higher proliferative and apoptotic indexes were detected in the diseased glands in comparison with normal controls. In neoplastic and secondarily hyperplastic glands, apoptotic indexes were higher than in primarily hyperplastic glands; the difference between neoplastic and primarily hyperplastic glands was statistically significant (P=0.034). Cyclin D1 was overexpressed in a considerable proportion of tumours (68.4%). A reduction of Fhit protein immunoreactivity was selectively noticed in carcinomas. CONCLUSIONS: In primary hyperplasia, the remarkable proliferation of parathyroid glands may be due to the reduction of the apoptotic process. FHIT gene abnormalities are worthy of investigation in parathyroid carcinogenesis.

Acid Anhydride Hydrolases↗

PubMed2002

Prognostic implications of microvessel morphometry in diffuse astrocytic neoplasms.

Astrocytic brain tumours, particularly malignant astrocytomas, are recognized to be highly vascular neoplasms with potent angiogenic activity. Recent research has shown that quantification of microvessel density (MVD), as a measure of the degree of angiogenesis, constitutes a strong prognostic indicator in patients with astrocytomas. However, the significance of other morphometric aspects of microvessel network has not been tested so far. In this report, histological sections from 70 astrocytomas (grades II to IV), immunostained for CD34, 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 vessel size or shape. Minor axis length increased with grade (P = 0.045) but MVD and TVA presented a peak in grade III (P = 0.033 and P < 0.001, respectively). Size and shape related parameters affected survival in univariate analysis of grade IV and grades II/III, respectively. In multivariate analysis, only branching counts, along with age and grade, were the independent predictors of survival. Although MVD, TVA and branching counts were adversely related to disease-free survival in grades II and III (univariate analysis), only TVA remained statistically significant in multivariate analysis. It is concluded that TVA and branching counts are prognostically more informative than MVD for patients with diffuse astrocytic tumours.

Adolescent↗

PubMed2002

Immunodetection and clinico-pathological correlates of two tumour growth regulators in laryngeal carcinoma.

Activation of telomerase, present in the vast majority of all human cancers, is associated with elongation of chromosomal telomeres and consequent cell immortalization. Telomere length homeostasis is a dynamic process governed by the negative feedback mechanism of the telomeric repeat binding factor 1 (TRF1) which inhibits the action of telomerase in telomerase-positive cells. In an attempt to investigate markers of tumour growth as possible prognostic indicators in laryngeal cancer, we studied the expression of TRF1 and of the proliferation marker Ki67 on 96 invasive squamous carcinomas of the larynx. A standard three step immunoperoxidase staining method was applied on paraffin sections incubated with appropriate polyclonal antibodies. The percentages of Ki67- and TRF1-immunopositive cancerous cells were calculated by image analysis. Univariate and multivariate statistical analysis of the staining results were performed in order to detect any association of the examined immunomarkers with the tumours' classical clinicopathological variables including nuclear morphometric features as well as with patients' disease-free survival. Ki67 immunostaining was positively linked with advanced patients' age, nodal involvement as well as presence of early recurrence. No relation was found between proliferative fraction and TRF1 immunoexpression. TRF1 was expressed in 55.2% of all cases and was positively linked only to tumour size. Multivariate statistical analysis revealed the presence of lymph nodal metastasis and Ki67 immunopositivity index > or = 20% as significant predictors of relapse. Increased Ki67 immunostaining appears to be a promising marker of tumour aggressiveness in laryngeal cancer. After one point at the tumour's natural history, the maintenance of tumour growth does not seem to depend on cell proliferation but on TRF1 immunoexpression. Whether the latter can be used for the identification of immortalized cells in every-day practice is worth investigating.

Adolescent↗

PubMed2002

Diagnostic approach of effusion cytology using computerized image analysis.

The objective of this study is to investigate whether image cytometry is a sensitive and specific method for the differential diagnosis of equivocal cells in routine cytology of effusion smears. One hundred four effusion smears were studied from routine cytologic material. Cytologically 56 (53.8%) of the smears were classified as malignant, 26 (24%) as suspicious and 22 (21.1%) as benign. Two morphometric variables (nuclear major axis length and nuclear area) of the nuclei were measured by an image analysis system. Higher values for the area were found for malignant rather than benign and suspicious cells (p < 0.0005 and p < 0.005 respectively). The same result was extracted for the nuclear major axis length values (p < 0.0005 and p < 0.0005 respectively). Values of nuclear major axis length and nuclear area didn't differ significantly between benign and suspicious cells (p = 0.071 and p = 0.066 respectively). The results show that the range of the values for suspicious cells is closer to the range of the benign cells. Cytomorphometry of the effusion smear cells may provide important information for the differentiation of atypical mesothelial cells from malignant adenocarcinoma cells.

Adenocarcinoma↗

PubMed2002

Computerized nuclear morphometry and quantitation of angiogenesis in thyroid neoplasms.

The aim of this study was to investigate the nuclear and angiogenetic profile in different types of thyroid neoplasms and to make any possible statistical comparison between the different nuclear morphometric and angiogenetic parameters, in order to search for new diagnostic and prognostic criteria. Sixty two cases of thyroid neoplasms were classified as follows: 31 papillary carcinomas, 10 follicular neoplasms (5 adenomas and 5 carcinomas), 5 undifferentiated carcinomas, 6 Huerthle-cell carcinomas and 10 medullary carcinomas. Using an image analysis system, six nuclear morphometric and eight angiogenetic variables were measured for each case. Concerning nuclear morphometric variables, statistical differences were found mainly between undifferentiated and overall subtypes of differentiated carcinomas, as well as between follicular adenomas and carcinomas. Concerning angiogenesis variables, statistical differences were found only in the vessel's minor axis length between undifferentiated and overall subtypes of differentiated carcinomas, between MVD of follicular adenomas and carcinomas respectively, as well as between MVD of medullary carcinoma and follicular cell carcinomas generally. In conclusion nuclear morphometry and quantitation of angiogenesis could offer two additional parameters in the distinction between follicular adenomas and carcinomas. However, they cannot serve as absolute diagnostic criteria since they are only based on statistical differences. From a prognostic point of view, nuclear morphometry may have some relevance as far as follicular-cell neoplasms are concerned since the more aggressive anaplastic carcinomas have a distinct morphometric profile. Moreover, our study revealed differences in the angiogenetic profile between medullary and follicular cell carcinomas.

Adenocarcinoma, Follicular↗

PubMed2001

Texture analysis of fluorescence microscopic images of colonic tissue sections.

The aim of this study was to assess the potential of texture analysis for the characterization of fluorescence images from colonic tissue sections stained with a novel and selective fluoroprobe, Rhodamine B-phenylboronic acid. Fluorescence microscopy images of colonic healthy mucosa (n = 35) and adenocarcinomas (n = 35) were digitally captured and subjected to image texture analysis. Textural features derived from the grey level co-occurrence matrix were calculated. A modified version of the multiple discriminant analysis criterion was used to choose an appropriate subset of features. A minimum Mahalanobis distance, linear discriminant classifier and a simple evaluation 'score' method were used to classify image feature data into the two categories. A subset of four textural features was selected and used for the description and classification of each image field. They were found appropriate to correctly classify 95% of the images into the two classes, using two different classifiers. These features contained information about local homogeneity and grey level linear dependencies of the image. This study demonstrated that texture analysis techniques could provide valuable diagnostic decision support in a complex domain such as colorectal tissue.

Adenocarcinoma↗

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↗