3D prostate histology reconstruction: an evaluation of image-based and fiducial-based algorithms.

PURPOSE: Evaluation of in vivo prostate imaging modalities for determining the spatial distribution and aggressiveness of prostate cancer ideally requires accurate registration of images to an accepted reference standard, such as histopathological examination of radical prostatectomy specimens. Three-dimensional (3D) reconstruction of prostate histology facilitates these registration-based evaluations by reintroducing 3D spatial information lost during histology processing. Because the reconstruction accuracy may constrain the clinical questions that can be answered with these data, it is important to assess the tradeoffs between minimally disruptive methods based on intrinsic image information and potentially more robust methods based on extrinsic fiducial markers. METHODS: Ex vivo magnetic resonance (MR) images and digitized whole-mount histology images from 12 radical prostatectomy specimens were used to evaluate four 3D histology reconstruction algorithms. 3D reconstructions were computed by registering each histology image to the corresponding ex vivo MR image using one of two similarity metrics (mutual information or fiducial registration error) and one of two search domains (affine transformations or a constrained subset thereof). The algorithms were evaluated for accuracy using the mean target registration error (TRE) computed from homologous intrinsic point landmarks (3-16 per histology section; 232 total) identified on histology and MR images, and for the sensitivity of TRE to rotational, translational, and scaling initialization errors. RESULTS: The algorithms using fiducial registration error and mutual information had mean ± standard deviation TREs of 0.7 ± 0.4 and 1.2 ± 0.7 mm, respectively, and one algorithm using fiducial registration error and affine transforms had negligible sensitivities to initialization errors. The postoptimization values of the mutual information-based metric showed evidence of errors due to both the optimizer and the similarity metric, and variation of parameters of the mutual information-based metric did not improve its performance. CONCLUSIONS: The extrinsic fiducial-based algorithm had lower mean TRE and lower sensitivity to initialization than the intrinsic intensity-based algorithm using mutual information. A model relating statistical power to registration error for certain imaging validation study designs estimated that a reconstruction algorithm with a mean TRE of 0.7 mm would require 27% fewer subjects than the method used to initialize the algorithms (mean TRE 1.3 ± 0.7 mm), suggesting the choice of reconstruction technique can have a substantial impact on the design of imaging validation studies, and on their overall cost.

Expression of vascular endothelial growth factor in uveal melanoma and its correlation with metastasis.

AIMS: To evaluate the expression of vascular endothelial growth factor (VEGF) in uveal melanomas and correlate its presence with tumour characteristics and systemic metastasis. METHODS: 47 cases of ciliochoroidal melanoma enucleated between 1983 and 1993 were retrieved from the pathology archives at the University of Western Ontario. Paraffin sections stained with haematoxylin and eosin, periodic acid Schiff, and periodic acid Schiff without haematoxylin after bleaching of melanin were examined. The expression of VEGF protein was examined by an immunoalkaline phosphatase method following antigen retrieval, using an antibody to VEGF and vector red as the chromogen. The intensity of VEGF immunoreactivity was graded on a scale of 0-7 and correlated with tumour cell type, tumour size, presence or absence of necrosis, pigmentation, mitotic activity, microvascular density, and microvascular pattern. RESULTS: VEGF immunoreactivity was present in 44/47 tumours (94%): the intensity was graded as very weak (1-2) in 29/47 (62%) and as weak or greater in 15/47 (32%). VEGF was also found in the ciliary epithelium, smooth muscle of the ciliary body and iris, retinal ganglion cells, inner photoreceptor segments, and the retinal pigment epithelium. Follow up data were available in 43/47 patients (91.5%), with a median follow up time of 10 years. 16/43 (37%) patients developed metastases. VEGF expression in melanoma was linked to the presence of tumour necrosis and the degree of pigmentation but no statistically significant relation with microvascular pattern, tumour size, or microvascular density was found. There was no statistically significant correlation between VEGF expression and metastasis. CONCLUSIONS: Most ciliochoroidal melanomas express VEGF and expression is correlated with the presence of necrosis but not with the occurrence of systemic metastasis or tumour angiogenesis.

Are there estrogen-receptors in human laryngeal cancers.

The presence of estrogen receptors in laryngeal carcinoma is controversial; with two independent methods (testing the binding of monoclonal antibodies against receptor protein by immunohistochemistry binding of labelled H-3-estradiol with the charcoal-dextran method), the levels of ER were found to be, if any, extremely low and without correlation to age, sex and previous radiation therapy of the patient. Administration of antiestrogens (if rationalized by the presence of ER) is therefore not indicated.

Primary gastric T-cell lymphoma of suppressor-cytotoxic (CD8+) phenotype: discordant expression of T-cell receptor subunit beta F1, CD7, and CD3 antigens.

Primary gastric T-cell lymphomas are rare neoplasms, and all but one of the previously phenotyped cases have shown a helper-inducer phenotype. The present case is the second reported case of a primary gastric T-cell lymphoma of suppressor-cytotoxic phenotype. The tumor histology was similar to that described in some forms of node-based peripheral T-cell lymphomas. Phenotypic analysis revealed low expression of pan-T marker CD7, reduced expression of CD3, but higher density and frequency of expression of CD8 antigens that could be predicted on the basis of the pan-T markers. Natural killer cell (NK) related markers CD16, HNK-1 and NKH-1 were not expressed by the neoplastic cells. T-cell receptor (TCR) beta subunit expression was detected on fewer cells than would have been predicted on the basis of CD3 and CD8 expression, and TCR delta chain expression was undetectable.