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H Dawkins

Publications and source records attributed to H Dawkins.

7 recordsLinked to original sources
PubMed2000

Assessment of endothelial cell proliferation in primary breast carcinoma and its association with axillary lymph node status.

The correlation between angiogenesis as assessed by endothelial cell proliferation in blood/lymphatic vessels in primary breast carcinomas, and axillary lymph-node metastasis was studied using a case-control design. Primary breast carcinomas, < 2 cm in diameter, from 26 axillary node positive patients (case), were compared with neoplasms from 45 node-negative patients (control). Vascularity, as assessed by vessel density, and endothelial cell proliferation were measured in a single tissue section using a double immunohistochemical staining technique using MIBI (Ki-67) and FVIII antibodies. No association between vascularity and node status was found (P > 0.70). Node positive breast carcinomas had, on average, significantly smaller proliferating vessels (140+/-7 microm in perimeter) in the primary lesion when compared with node negative tumours (164+/-7 microm in perimeter (P < 0.02). In addition, the frequency of relatively small vessels (less than 180 microm in perimeter) with proliferating endothelium was higher in node positive carcinomas than lymph-node negative neoplasms (P < 0.03). This association between node status and the size and frequency of blood/lymphatic vessels with proliferating endothelium in primary carcinoma may have important implications in metastasis.

Journal Article↗
PubMed1995

Histological grading of breast carcinomas: a study of interobserver agreement.

Interobserver variation in the histological grading of breast carcinoma was investigated using the hypothesis that optimal fixation, more precise grading guidelines, some experience, the use of training and test sets, and a comparison of results with an expert group might allow higher levels of agreement. For the training sets sections from 50 consecutive cases of breast carcinoma received at the Sir Charles Gairdner Hospital (SCGH) and fixed in both B5 and buffered formal saline (BFS) were graded by consensus of three pathologists at the SCGH and independently by consensus of two pathologists at the Nottingham City Hospital (NCH) using a modified Scarff-Bloom-Richardson histological grading system with guidelines as suggested by NCH pathologists. The section quality and degree of preservation of nuclear morphology were judged by NCH pathologists to be superior for B5-fixed material. Complete agreement in grade between SCGH and NCH results was achieved for 83.3% of B5-fixed cases and 73.5% of BFS-fixed cases (P = .05) with relative disagreement rates (RDRs) of 0.15 and 0.29 and kappa statistic values of 0.73 and 0.58, respectively. Approximately 80% complete agreement was achieved for tubule formation, nuclear score, and mitotic count, with RDRs ranging from 0.19 to 0.27 and kappa values from 0.46 to 0.69. There was a consistent bias in the SCGH results toward a higher tubule score in both B5- and BFS-fixed material because of a difference in interpretation of cribriform or complex gland patterns and a consistent bias in SCGH results toward a lower nuclear size/pleomorphism score for B5 and BFS material. For the test set sections from 50 further consecutive cases of breast cancer fixed in B5 were examined using similar criteria but taking into account the sources of error shown by the training set. Approximately 80% complete agreement was again achieved for grade components and grade (RDRs, 0.18 and 0.72). Systematic bias was reduced in the test set, but no other improvement was observed. Of the tumors designated as grade I by NCH, 87.5% were called grade I tumors by SCGH in the B5 training set, 84.6% in the B5 test set, and 66.6% in the BFS training set. The levels of agreement shown in both the training and test sets were satisfactory and represented a significant improvement over our previous study, suggesting that experience and precise grading guidelines are of value. The similar levels of agreement in training and test sets suggest that reasonable results can be achieved without direct training by expert groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Breast Neoplasms↗
PubMed1995

Fine deletion mapping on the long arm of chromosome 9 in sporadic and familial basal cell carcinomas.

Basal cell carcinomas (BCCs) are the most common sporadic cancers worldwide. They are also a cardinal manifestation of a familial cancer predisposition syndrome, naevoid BCC syndrome (NBCCS). The gene responsible for NBCCS is likely to be a tumour suppressor gene and has been genetically mapped to a 2cM region between microsatellite markers, D9S196 and D9S180 at 9q22.3-q31. 101 BCCs (63 sporadic and 38 familial) were examined for loss of heterozygosity (LOH) in the candidate region of the NBCCS gene. Deletions were found in 46% and all LOH is consistent with genetic mapping of the NBCC locus. These findings strongly support the hypothesis that inactivation of the putative tumour suppressor, the NBCCS gene, is important in the formation of sporadic BCCs. One sporadic tumour indicates that the smallest region of overlap of these deletions is within the interval between D9S287 and D9S180. If this is confirmed in additional tumours, it would further narrow down the NBCCS region and exclude one candidate gene, that for the C complementation group of Fanconi anaemia, which maps proximally to D9S287. However, it would not exclude another candidate, the gene for the A complementation group of xeroderma pigmentosum (XPAC). Evidence of imprinting was also sought but preliminary data indicate that it is unlikely to occur at the NBCCS locus.

Adult↗
PubMed1994

Expression of stromelysin-3 and nm23 in breast carcinoma and related tissues.

Biological functions proposed for the ST3 and nm23 genes in tumour development and progression seem to be directly opposed. Stromelysin-3 (ST3) is a putative member of the matrix metalloproteinase family. ST3 has been implicated in the progression of epithelial malignancies, specifically with regard to an invasive (and therefore potentially metastasizing) phenotype. The nm23 gene, on the other hand, encodes a nucleoside diphosphate kinase which allegedly has a metastasis-suppressor-type function. It was therefore of interest to compare the expression of ST3 and nm23 in various surgically excised normal and neoplastic breast tissues. RNA was isolated from over 200 surgical specimens and studied by Northern blots. Normal breast tissues did not express ST3, and ST3 expression was detected in only 1 of 20 normal axillary lymph nodes. None of 7 fibroadenomas expressed ST3. In contrast, 60% of primary and metastatic breast carcinomas contained ST3-mRNA. The expression of ST3 was mainly confined to invasive carcinomas and was observed less frequently in pure ductal carcinoma in situ (DCIS) lesions. Our results support the suggestion that ST3 expression is related to the malignant process in breast cancer. The role of nm23 is far less clear-cut.

Biopsy↗
PubMed1994

The relative prognostic significance of total cathepsin D and HER-2/neu oncogene amplification in breast cancer. The South Australian Breast Cancer Study Group.

Total tumor cathepsin D (TCD) levels were determined prospectively by a radioimmunometric assay in tumor cytosol of 858 primary breast cancer patients diagnosed between 1989-1991. In 581 of these patients, tumor HER-2/neu oncogene amplification was simultaneously determined. In a "training-set" of 313 patients, "high" TCD was associated with significantly shorter disease-free survival (DFS). For the whole group, there was no correlation between TCD and pathologic stage, number of axillary nodes with tumor deposits, tumor size, histologic type and grade, or hormone receptor levels. In the node-positive group, high TCD level was associated with HER-2/neu amplification. After a median follow-up duration of 31 months, univariate analysis indicated that high TCD level was significantly associated with shorter DFS only in node-positive patients. The shorter DFS in association with high TCD levels was observed in both estrogen-receptor-positive and -negative patients. Cox multivariate analysis of DFS confirmed that high TCD level was predictive of shorter DFS in node-positive patients only. Because of the short duration of follow-up, the significance of TCD in overall survival was not determined. We conclude that high tumor TCD in node-positive patients is predictive of shorter DFS, and is often associated with HER-2/neu amplification. The possibility exists that high tumor TCD may act in combination with HER-2/neu amplification to promote dissemination of metastases.

Adult↗
PubMed1968

Darier's disease.

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Darier Disease↗