Prognostic significance of cell kinetics in laryngeal squamous cell carcinoma: clinicopathological associations.

A consecutive series of 99 untreated patients undergoing radical surgical resection for stage I-IV laryngeal carcinomas has been studied prospectively. Our purpose was to analyze the predictive relevance of proliferative variables studied [proliferating cell nuclear antigen (PCNA) expression, volume-corrected mitotic (M/V) index, and S-phase fraction (SPF)] on clinical outcome in relation to DNA ploidy and clinicopathological features. All of the patients were followed up for a median of 32 months (range, 5-58 months). A weak, but significant, positive correlation was found between M/V and PCNA indices (except the PCNA weighted mean index:labeling index ratio) or these indices and SPF. At univariate analysis, node positivity (P < 0.05), poor histological grade (P < 0.01), DNA aneuploidy (P < 0.01), a high SPF (P < 0.01), and a high M/V index (P < 0.05) proved to be related significantly to quicker relapse, whereas T4 (P < 0.05), subglottic site (P < 0.05), DNA aneuploidy (P < 0.01) and a high SPF (P < 0.01) were related significantly to shorter overall survival. With multivariate analysis, a high SPF (> 12.1%) and histological grade (G3) were related to the risk of relapse (relative risk, 8.65 and 5.45, respectively), whereas only a high SPF was related independently to the risk of death (relative risk, 7.30). Our study has identified SPF, in addition to histological grade, as an important biological indicator in laryngeal carcinomas.

Pleomorphic adenoma and adenoid-cystic carcinoma of salivary glands: immunohistochemical assessment of proliferative activity in comparison with flow-cytometric study.

In this study, 32 pleomorphic adenomas (PAs) and seven adenoid cystic carcinomas (ACCs) were analysed for the evaluation of proliferating cell nuclear antigen (PCNA) indices and flow cytometric variables. Our aim was to assess any possible relationship between these parameters and the clinico-pathological variables and to clarify their histogenesis and reasons for their biological differences. The tumours were divided into three groups, mainly epithelial (E), myxoid (M) and chondroid (C); PCNA labelling index (LI) and weighted mean index (WI) and the WI/LI ratio were analysed in the predominant components; a single PCNA index, weighted by the percentage of each component, was also calculated. Only WI/LI was found to be significantly different in the three components, while PCNA single index did not show either significant differences by sex, age, site and size, or any correlation with the S phase fraction. A significant difference was found between PAs and ACCs by site (P < 0.01) and DNA ploidy (P < 0.05); furthermore, all PCNA indices (single index) were significantly lower in PAs than in ACCs.

P53 expression in stage iii-iv squamous-cell carcinoma of the larynx - an immunohistochemical study related to clinicopathological, flow-cytometric DNA analysis and prognosis.

A series of 71 patients undergoing radical surgical resection for stage III and IV laryngeal carcinoma (LC) consecutively diagnosed was prospectively studied in order to evaluate the relative weight of p53 expression in predicting clinical outcome, All the patients taking part in this study were followed up for a median of 18 months (range: 6-41 months). Positive staining for p53 protein was detected in 44 of 71 (62%) of these tumors on paraffin-embedded tissue, even in dysplastic areas. Among the clinico-pathological and biological parameters analyzed, only flow-cytometric S-phase (FCM-S) Values of turners showed a significant relationship to p53 immunostaining (p=0.01). With Kaplan-Meier estimation, in multivariate analysis only high FCM-S (>15.1) was independently related to risk of relapse (RR=5.82), while both FCM-S and site (subglottis) were related to risk of death (RR=6.83 and RR=14.3, respectively). These findings indicate that p53 immunoreactivity, though of no utility as a prognostic indicator, probably plays a role in the early stages of LC tumorigenesis.

Prognostic value of clinicopathologic variables and DNA ploidy in stage I cutaneous malignant melanoma.

We studied a consecutive series of 78 stage I cutaneous malignant melanoma in order to identify variables which might predict development of metastases. Anatomical site, sex, tumor thickness, Clark level, microscopic ulceration, growth phase, histologic type, cell type, and DNA ploidy were investigated. Lesions with tumor thickness 1.5 mm, Clark level IV-V, microscopic ulceration and DNA aneuploidy were at high risk for the development of metastases. This study showed the prognostic importance of DNA ploidy in stage I cutaneous malignant melanoma and the strong relationship between DNA ploidy and classic prognostic factors. This variable can be used in routine diagnosis for selecting a high-risk group of patients who may benefit from a more aggressive therapeutic approach.

Malignant myoepithelioma of the breast - a case-history and review of literature.

A malignant myoepithelioma, mainly intraductally growing, of the breast was studied, emphasizing the immunohistological features of such tumors, in comparison with the more common, architecturally similar, infiltrating ductal carcinoma with intraductal component. Immunohistochemically, cell population of the tumor studied expressed intense reaction to alpha-SM-actin, cytokeratin 14, vimentin, S-100 protein and collagen IV antibodies, confirming myoepithelial differentiation. Since myoepitheliomas of the breast are very rare, complete knowledge of these neoplasms has not been attained. Nevertheless, histogenetic investigations may be useful in differentiating this type of tumor, from the above one, which is known to be characterized by severe clinical and prognostic implications.

Epithelial-myoepithelial carcinoma of the salivary glands: a review of literature.

Epithelial-myoepithelial carcinoma (EMC) of the salivary glands is a rare tumor first described by Donath et al in 1972 and recognized as a distinct pathologic entity in the 1991 WHO classification. The EMC comprises approximately 1% of all salivary gland tumors. The histological hallmark is a biphasic cell arrangement formed by an inner layer of duct-forming epithelial cells and an outer layer of myoepithelial cells. The epithelial-myoepithelial dualism is confirmed using immunohistochemical methods: the epithelial cells are immunoreactive for low molecular weight keratin; the myoepithelial cells are immunoreactive for S-100 protein, muscle specific actin and vimentin. Most reported follow-up information indicates that EMC is a low-grade malignant tumor; however, from the analysis of the various series it is demonstrated that tumors with a solid growing pattern, nuclear atypia, DNA aneuploidy and high proliferative activity, generally have a more aggressive behavior and a higher frequency of local recurrences and metastases.

Prognostic factors in oral squamous cell carcinoma. A review of the literature.

Despite diagnostic and therapeutic progress, the overall prognosis of oral squamous cell carcinoma remains poor and prognostic information is essential for the evaluation and optimal treatment of patients. The prognosis of oral carcinoma depends primarily on clinicopathological factors, that however, have showed a limited predictive value for the identification of patients with high risk of disease relapse. In recent years, the analysis of DNA ploidy, cellular proliferation and oncogenes amplification have been used in attempt to identify new prognostic indicators. The review of the literature shows that TNM stage, tumor grading evaluated at the deep invasive margins and maximal tumor thickness effect on the prognosis. Moreover, the assessment of DNA ploidy and proliferative activity can be used to obtain additional prognostic informations. In contrast, additional studies are needed to understand the prognostic value of oncogenes expression in oral carcinoma.

Malignant myoepithelioma of the minor salivary glands arising in a pleomorphic adenoma.

This paper reports a case of carcinoma expleomorphic adenoma of the minor salivary glands, where the carcinomatous component was a malignant myoepithelioma (myoepithelial carcinoma). Immunohistochemical investigation showed that the carcinoma cells were positive for cytokeratin, S-100 protein and vimentin, and focally positive for actin and desmin. A moderate level of positivity was found fo laminin and collagen IV around the neoplastic islands. These data are the confirmation that the carcinoma cells were myoepithelial. The number of mitoses, the istotype, the minimal extent of extracapsular infiltration and the absence of vascular invasion made it possible to include this particular case among those with a better prognosis.

Epithelial-myoepithelial carcinoma of the salivary glands: a clinico-pathologic, immunohistochemical and DNA flow cytometric study of three cases.

Epithelial-myoepithelial carcinoma is a rare neoplasia of the salivary glands. Histologic, immunohistochemical and flow cytometry analysis were used to study three new cases involving the major salivary glands of two women and one man. The mean age was 66.7 years. Immunohistochemistry confirmed the epithelial-myoepithelial dualism of the tumors: the predominant growth pattern showed ducts made up of an external myoepithelial layer and an internal epithelial layer. Proliferative activity, assessed by means of the PCNA and Ki-67 immunostaining and the study of the S-phase with flow cytometric analysis, proved to be higher in a recurrent case. All three cases were diploid. The use of immunohistochemical and flow cytometric techniques for the assessment of proliferative activity would seem to be an efficient method for the selection of a subgroup of epithelial-myoepithelial carcinomas with unfavorable prognosis.

Node status in lower lip squamous cell carcinoma in relation to tumor size, histological variables and DNA ploidy.

We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma (LLSCC) in order to identify any variables which might predict the development of lymph node metastases. The cases were divided into 38 tumors without metastases (group I) and 16 tumors with lymph node metastases (group II). The following variables were investigated: tumor size, histologic grading, tumor maximal thickness, perineural infiltration and DNA ploidy, in a group of patients undergoing surgical treatment for LLSCC, and to show which of these might be predictive of the development of lymph node metastases.

Polymorphous low-grade adenocarcinoma of the salivary glands: clinicopathological and immunohistochemical study of a case.

Polymorphous low-grade adenocarcinoma (PLGA) is a distinctive salivary gland neoplasm with a predilection for intraoral sites. Histological and immunohistochemical analyses were used to study a case involving the minor salivary glands of the buccal mucosa in a 68-year-old woman. Histologically, the tumor was characterized by unenca-psulated, progressing and focally-infiltrative borders and showed variable growth patterns including solid, tubular, microcystic and cribriform; papillary and papillary-cystic areas of more than focal extent were present. Cytologically the neoplasm was composed of uniform, round to cuboidal cells with bland, round to oval nuclei. Immunohistochemical analysis showed that the tumor cells were positive for cytokeratin, S-100 protein, vimentin, focally-positive for EMA and actin and negative for CEA. The significance of the papillary component and the possible relationship to other salivary gland tumors is discussed.

Biological characterization of laryngeal squamous-cell carcinoma.

The traditional prognostic factors, including stage of disease and tumour grade, have shown a limited prognostic significance and an inability to predict clinical response to specific treatment in patients with laryngeal squamous-cell carcinoma. More recent data suggest that cell kinetics indices, DNA-ploidy, lysosomal cysteine proteinase expression and genetic changes of both tumour suppressor genes and protooncogenes may be considered as reliable and reproducible indicators of biological aggressiveness in these patients. Moreover, the frequency of different genetic alterations suggests that several pathways are involved in the genesis of these neoplasias and, in particular, it is very probable that p-53 expression and PCNA indices (increased in normal mucosa and preinvasive lesions) may constitute more important biomarkers for the early steps of laryngeal carcinogenesis.

Prognosis in lower lip squamous cell carcinoma: assessment of tumor factors.

We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma (LLSCC) in order to identify any variables which might predict the development of lymph node metastases. The cases were divided into 38 tumors without metastases (group I) and 16 tumors with lymph node metastases (group II). The following factors were investigated: tumor size, histologic grading maximal thickness, perineural invasion, DNA ploidy and PCNA expression. In conclusion, we found that LLSCC greater than 2 cm in diameter, with histological grading G3-G4, thickness of more than 6 mm, DNA aneuploidy and high PCNA expression (PCNA LI > 0.48), were at high risk for the development of lymph node metastases.

Evaluation of integrated morpho-biological indicators in breast cancer.

A series of 71 patients undergoing surgery for primary breast carcinoma was prospectively studied in order to verify the relationships between clinical and pathological variables, proliferative indexes and DNA-ploidy. Significant correlations between proliferative indexes were found; conversely, DNA-ploidy showed no correlation with either PCNA/cyclin or AgNORs, but only with flow cytometry S-phase fraction (FCM-S) and IF-vimentin. In the 42 patients with a mean follow-up of 42 months, disease-free rate was best predicted by nuclear grade (p < 0.001), histological grade (p < 0.001), mitoses (p 0.001), IF-vimentin (p 0.002), FCM-S (p 0.002), PCNA (p 0.005) and Ag-NORs (p 0.007).

[Micro-glandular hyperplasia of the uterine cervix. Histo-cytopathological evaluation, differential diagnosis and review of literature]. / L'iperplasia microghiandolare della cervice uterina. Valutazioni isto-citopatologiche, diagnosi differenziale e revisione della letteratura.

Microglandular hyperplasia is a lesion of the uterine endocervical mucosa, often associated with a story of contraceptive drugs or pregnancy. It was frequently confused with adenocarcinoma or premalignant glandular changes until its benign nature was recognized. In order to ascertain clinical presentation, hormonal or gestational status, histologic patterns with their variants and cytologic counter-part, we collected and reviewed 28 cases of this condition over a period of a decade. The age ranged from 23 to 54, with a mean of 37.2 years. 11 patients had been receiving oral contraceptives and 5 were pregnant. All samples came from uterine cervix. Cervical smears were available from 17 women. Four histologic patterns were identified, including glandular, reticular, trabecular and solid. Cytologic features varied from aspecific, inflammatory changes of the columnar endocervical cells to more particular findings, including clear cells, strips, sheets, papillae, rosettes and corolla-like aggregates. Moreover, differential diagnostic criteria from cervical neoplasms and various pseudoneoplastic conditions of the cervical glandular epithelium are discussed. An extensive review of the literature is also presented.

[Collagenous colitis. Morphologic and immunohistochemical study]. / Colite collagena. Studio morfologico ed immunoistochimico.

Collagenous colitis is a clinico-pathological entity characterized by chronic diarrhoeas and deposition of collagen beneath the epithelium surface of large bowel. We revised 265 endoscopy biopsy specimens of the large bowel from 198 consecutive patients with "aspecific chronic colitis". Morphometric study showed that were not significant differences among various tracts in the same patients regarding to the thickness of basament membrane. It was more than 11.9 +/- 0.49 mu only in 13 pts (6.6%), while it was 3.96 +/- 1.4 mu in the others. Immunohistochemistry study confirmed the normality of subepithelial basement membrane and the below deposition of the large quantity of collagen IV.

p53 expression in human renal cell carcinoma: an immunohistochemical study and a literature outline of the cytogenetic characterization.

In this study both the incidence and pattern of p53 over-expression in various histological subtypes of a series of 36 cases of renal cell Grawitz carcinoma, partially studied in a previous paper, were analyzed. This series consisted of these histologic subtypes: clear cell non papillary (18 cases), clear cell papillary (2 cases), granular cell (5 cases), mixed (clear and granular cell) (9 cases) and spindle cell (2 cases). At present, our aim was, firstly, to see which were the best technical conditions for detection of p53 in the available paraffin-embedded tumor specimens, using several antibodies, specific for various epitopes; secondly, to investigate if some relation might exist between this expression and the histological features of these tumors. Twenty-five per cent (9/36 cases) resulted p53 immunoreactive, the highest percentage being represented in the papillary clear and granular cell carcinomas; low expression was detected in 11 cases (30%) and no reactivity in 16 cases (44%). Neither technical or dilution modifications proved to transform these latter results; however, detection was maximal using the CM-1 polyclonal rabbit antiserum. Thus, in RCC, expression of p53, analyzed in the light of the cytogenetic characterization through a literature review, resulted at low frequency. This finding means that mutation of the p53 gene are not frequent in the neoplastic transformation in RCC. Nevertheless, in spite of the small number of cases and of the short follow-up period of this study, detection of p53 positivity in tumors with either high grade and stage or high proliferative activity could suggest that p53 mutations lead to tumors of a more aggressive type.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal cell (Grawitz) carcinoma: an immunohistochemical study in correlation with nuclear grade, histological pattern and proliferative activity of tumor cells.

Since morphological features of renal cell carcinomas may not always predict their clinical behaviour, other biological parameters are more and more searched for, as prognostic indicators. Among those, the Authors evaluate the cytokeratin-vimentin intermediate-sized filaments co-expression in a series of 32 renal carcinomas and analyze this feature in correlation with both traditional criteria and proliferative activity of tumor cells, studied by means of the proliferation cellular nuclear antigen (PCNA) expression as well as of the nucleolar organizer regions (NORs) count, within tumor cells. From this study, nuclear grade stands out as the best parameter which, furthermore, shows a significant relationship with the cytokeratin-vimentin co-expression and the mean NORs count in tumor cell populations. Further investigations about relationships between these parameters and survival of the patients, who, at present, are almost all alive, will be performed afterwards.

Vimentin expression, proliferating cell nuclear antigen and flow cytometric factors. Prognostic role in breast cancer.

A series of 71 patients undergoing surgery for primary breast carcinoma was prospectively studied in order to evaluate the relative weight for four biologic factors (intermediate filament vimentin expression, proliferating cell nuclear antigen [PCNA], flow cytometric DNA ploidy and S-phase fraction) and of several clinicopathologic and biologic features in predicting clinical outcome (disease-free interval). In univariate statistical analysis, positivity of axillary nodes, high number of mitoses, high nuclear grade, high histologic grade, positivity of vimentin, high flow cytometric S-phase fraction (FCM-S) value, high PCNA and high silver-stained nuclear organizer regions scores were significantly related to risk of relapse. In multivariate analysis (Cox's logistic regression) only histologic grade (3) and high FCM-S values (> 10.7) were independently related to risk of relapse, with hazard ratios of 9.84 and 7.98, respectively. The results of our preliminary, prospective study suggest that FCM-S, in addition to morphologic criteria (histologic grade), may be an important biologic indicator in determining breast cancer patients' prognosis.