Uveal melanoma: the importance of large nucleoli in predicting patient outcome--an automated image analysis study.

BACKGROUND: Automated image capture and analysis (AICA) has not previously been used to measure the size of nucleoli in uveal melanoma. In this study, the measurements were tested for a possible association with patient outcome. METHODS: Sections from 63 uveal melanomas were stained using the silver stain for nucleolar organizing regions (AgNOR). AICA was used to measure the following five nucleolar features in ten microscopic fields of the tumor: area, circularity, maximum diameter, width, and length of the perimeter. For each tumor, the mean and standard deviation of each of the features were calculated based on all the nucleoli and on subsets of nucleoli with larger areas. For the five nucleolar features the mean of the largest value (MLV) in each of the ten fields was calculated. For comparison, a related visually measured nucleolar feature (MLN) was obtained from hematoxylin and eosin stained sections using a filar micrometer. RESULTS: Thirty-four patients died with metastatic disease and 29 patients survived at least 5 years without metastasis. A greater proportion of nucleoli larger than 3 mm2 in greatest dimension were from patients who died of their disease. The means of the nucleolar features were less significant outcome discriminators than the standard deviations. Means and standard deviations based on subgroups of nucleoli larger than 3 or 3.5 mm2 in greatest dimension were better discriminators. The MLVs were as effective discriminators as the corresponding standard deviations of the larger nucleoli and were better discriminators than MLN. CONCLUSIONS: AICA of AgNOR stained sections of uveal melanoma provides an excellent method for predicting the outcome of patients with uveal melanoma.

Choroidal-ciliary body melanoma. A multivariate survival analysis of tumor location.

BACKGROUND: Posterior uveal melanomas with ciliary body involvement have greater mortality when compared with choroidal melanomas. This study was conducted to determine if this association is due to an independent effect or to correlations with other parameters. METHODS: From the 4335 cases of uveal melanoma with follow-up data in the Registry of Ophthalmic Pathology, 664 were selected; therefore, approximately two thirds of the patients died of metastatic melanoma. Ciliary body involvement was determined by the location of the anterior tumor margin. Kaplan-Meier survival, Cox regression, and Gamel-Boag log-normal regression analyses were performed. Covariables included ciliary body involvement, largest tumor dimension, mean diameter of the largest ten nucleoli, and modified Callender classification. RESULTS: Kaplan-Meier and univariate Cox analyses indicated a significant association between ciliary body involvement and tumor-related death but when included in a multivariate Cox model, ciliary body involvement was not statistically significant. Similarly, when ciliary body involvement was included in a multivariate Gamel-Boag model, ciliary body involvement was not statistically significant. Melanomas that involve the ciliary body were more likely to be larger (Student's t = 10.5; P = 10(-6)), contain larger nucleoli (Student's t = 2.43; P = 0.015), and be of mixed cell type (chi-square = 17.2; P = 3 x 10(-5)). CONCLUSIONS: Ciliary body involvement is associated with tumor-related mortality but this association is primarily due to ciliary body tumors being larger with more malignant cytology.

Biologic distinctions between cure and time to death in 2892 patients with intraocular melanoma.

BACKGROUND: For certain types of cancer, resection alone rarely achieves a cure, but patients nevertheless tend to have a prolonged survival before they die of the tumor. For other types of cancer, the opposite scenario prevails, suggesting that those biologic mechanisms that allow a curative resection are not identical to those that determine survival time among uncured patients. METHODS: The multivariate log-normal model can be used to detect the association of cured fraction and median survival time of patients with specific prognostic covariates. This model was applied to survival data from 2892 patients with intraocular melanoma who were treated by enucleation. RESULTS: This analysis showed that large tumor size and pleomorphic nucleoli within the tumor were associated independently with a low probability of cure and short median survival time. Advanced patient age and mixed cell type, however, were highly associated with only a short median survival time. CONCLUSIONS: For patients with intraocular melanoma treated only by enucleation, the median survival time is not modulated by the same biologic factors that determine the likelihood of a curative resection.

A comparison of prognostic covariates for uveal melanoma.

For 740 selected cases of uveal melanoma from the Armed Forces Institute of Pathology, the following features were determined: the age and sex of the patient, Callender cell type (CT), and largest tumor dimension (LTD). In addition, special morphometric devices were used to measure the standard deviation of nucleolar area (SDNA) and the mean of the largest nucleoli (MLN) from a single routine hematoxylin and eosin-stained section of each tumor. Univariate analysis using the Cox proportional-hazards model revealed that LTD, CT, SDNA, and MLN correlated equally with death from metastatic melanoma (P greater than 10(-6). Age correlated less highly (P less than 0.002), and sex had no relationship to mortality. Multivariate analysis revealed that adding LTD as a prognostic covariate to either CT, SDNA, or MLN yielded a substantial increase in prognostic value. Because MLN can be measured more easily than SDNA and is more reproducible than CT, it can be a useful cytologic index of the malignant potential of uveal melanomas.

Enhancement of bactericidal capacity of alveolar macrophages by human alveolar lining material.

In vivo studies have shown a major role for the alveolar macrophage in the killing of inhaled bacteria. This contrasted with earlier work which showed a preservation of phagocytic properties but a loss of bactericidal capacity when alveolar macrophages were studied in vitro. Recently, alveolar lining material (ALM) from rats has been shown to enhance the in vitro bactericidal capacity of alveolar macrophages from homologous animals against Staphylococcus aureus. Utilizing a similar system, we have confirmed that rat alveolar macrophages do not kill S. aureus in vitro unless the bacteria have been incubated with rat ALM (R-ALM) before phagocytosis. In addition, human ALM (H-ALM) from 7 of 11 patients assayed showed an enhancement of bactericidal capacity by rat alveolar macrophages which was not significantly different from the results utilizing R-ALM. H-ALM from the other four patients gave results which differed significantly from results with H-ALM from the first seven patients and R-ALM (P less than 0.001). Preliminary results suggest that the factor enhancing the bactericidal capacity of rat alveolar macrophages is present in the lipid fraction of the ALM. Further characterization of the ALM is warranted in an effort to explain the enhancement of the bactericidal capacity of alveolar macrophages by most, but not all, H-ALM tested.